The mRNA for the peptide hormone is transferred to the cytoplasm and translated on the ribosomes to the first protein product, a (...).

preprohormone

The signal peptide is removed from the preprohormone in the endoplasmic reticulum, converting the it to a (...).

prohormone

The prohormone is transferred to the Golgi apparatus, where it is packaged in (...).

secretory vesicles

In the secretory vesicles, proteolytic enzymes cleave peptide sequences from the prohormone to produce the final (...).

hormone

The final hormone is stored in (...) until the endocrine cell is stimulated.

secretory vesicles

The steroid hormones are cortisol, aldosterone, estradiol and estriol, progesterone, testosterone, and 1,25-dihydroxycholecalciferol, which are derivatives of (...).

cholesterol

The amine hormones are catecholamines and thyroid hormones, which are derivatives of the amino acid (...).

tyrosine

Adjustments in secretory rates of hormones may be accomplished by (...) mechanisms or by (...) mechanisms.

neural; feedback

(...) mechanisms of hormone control are illustrated by the secretion of catecholamines.

neural

(...) mechanisms are the most common mechanism of hormone control.

feedback

(...) feedback means that some feature of hormone action inhibits further secretion of the hormone.

negative

(...) feedback means that the hormone feeds back all the way to the hypothalamic-pituitary axis.

long-loop

(...) feedback means that the anterior pituitary hormone feeds back on the hypothalamus.

short-loop

(...) feedback means that the hypothalamic hormone inhibits its own secretion.

ultrashort-loop

(...) feedback is an uncommon mechanism of hormone control in which some feature of hormone action causes more secretion of the hormone.

positive

The primary example of positive feedback is the effect of (...) on the secretion of gonadotropins by the anterior pituitary at the midpoint of the menstrual cycle.

estrogen

A second example of hormonal positive feedback is (...), which is secreted by the posterior pituitary in response to dilation of the cervix.

oxytocin

The responsiveness of a target tissue to a hormone is expressed in the (...) in which the magnitude of response is correlated with hormone concentration.

dose-response relationship

(...) is defined as the hormone concentration that produces 50% of the maximal response.

sensitivity

(...) means that the number or the affinity of the receptors for the hormone has decreased.

down-regulation

(...) means that the number or the affinity of the receptors for the hormone has increased.

up-regulation

The major mechanisms of hormone action on target cells are (1) the (...) mechanism, in which cAMP is the second messenger; (2) the (...) mechanism, in which IP₃/Ca²⁺ is the second messenger; and (3) the (...) mechanism.

adenylyl cyclase; phospholipase C; steroid hormone

Insulin and insulin-like growth factors (IGFs) act on their target cells through a (...) mechanism.

tyrosine kinase

Several hormones activate (...), in which cyclic guanosine monophosphate is the second messenger.

guanylate cyclase

G proteins can be either stimulatory or inhibitory and are called, accordingly, (...).

G_s (stimulatory) or G_i (inhibitory)

When no hormone is bound to the receptor, the α_s subunit of the G_s protein binds (...); In this configuration, the G_s protein is (...).

GDP; inactive

When hormone binds to its receptor in the cell membrane, (...) is released from the α_s subunit and is replaced by (...), and the (...) detaches from the G_s protein.

GDP; GTP; α_s subunit

The α_s-GTP complex migrates within the cell membrane and binds to and activates (...).

adenylyl cyclase

Activated adenylyl cyclase catalyzes the conversion of adenosine triphosphate (ATP) to (...), which serves as the second messenger.

cAMP

cAMP, via a series of steps involving activation of (...), phosphorylates intracellular proteins.

protein kinase A

Intracellular cAMP is degraded to an inactive metabolite, (...), by the enzyme (...), thereby turning off the action of the second messenger.

5′ adenosine monophosphate (5′ AMP); phosphodiesterase

With no hormone bound to the receptor, the α_q subunit binds (...); In this configuration, the G_q protein is (...).

GDP; inactive

When hormone binds to its receptor in the cell membrane, (...) is released from the α_q subunit and is replaced by (...), and the (...) detaches from the G_q protein.

GDP; GTP; α_q subunit

The α_q-GTP complex migrates within the cell membrane and binds to and activates (...).

phospholipase C

Activated phospholipase C catalyzes the liberation of (...) and (...) from phosphatidylinositol 4,5-diphosphate (PIP₂).

diacylglycerol; IP₃

The IP₃ causes the release of (...) from intracellular stores in the endoplasmic or sarcoplasmic reticulum.

Ca²⁺

Ca²⁺ and diacylglycerol activate (...), which phosphorylates proteins and produces the final physiologic actions.

protein kinase C

Some hormones bind to cell surface receptors called (...) that have, or are associated with, enzymatic activity on the intracellular side.

catalytic receptors

What are the four types of catalytic receptors?

1. guanylyl cyclase
2. serine/threonine kinases
3. tyrosine kinases
4. tyrosine kinase–associated receptors

Atrial natriuretic peptide (ANP) acts through a (...) mechanism.

receptor guanylyl cyclase

Nitric oxide (NO) acts through a (...) mechanism.

cytosolic guanylyl cyclase

(...) and (...) phosphorylate serine and threonine in the cascade of events leading to their biologic actions.

Ca²⁺-calmodulin-dependent protein kinase (CaMK); mitogen-activated protein kinases (MAPKs)

(...) have intrinsic tyrosine kinase activity within the receptor molecule; (...) do not have intrinsic tyrosine kinase activity but associate with proteins that do.

receptor tyrosine kinases; tyrosine kinase–associated receptors

The tyrosine kinase receptor for nerve growth factor (NGF) and epidermal growth factor receptors is a (...) which (...) after binding of ligand.

monomer; dimerizes

The tyrosine kinase receptor for insulin and insulin-like growth factor (IGF) is a already a (...).

dimer

The tyrosine kinase–associated receptor for growth hormone receptors is noncovalently “associated” with the (...) pathway.

JAK-STAT

In contrast to peptide hormones, steroid hormones and thyroid hormones bind to (...) receptors and have a (...) onset of action.

cytosolic (or nuclear); slower (taking hours)

The steroid hormone diffuses across the cell membrane, where it binds to a specific (...) that is located in either the cytosol or nucleus.

receptor protein

The steroid hormone binds in the (...) of the steroid receptor protein located near the C terminus.

E domain

The central (...) of the steroid receptor protein is highly conserved, has two zinc fingers, and is responsible for DNA binding.

C domain

The steroid hormone-receptor complex dimerizes and binds (at its C domain) via the zinc fingers to specific DNA sequences, called (...).

steroid-responsive elements (SREs)

After binding to the SRE, the hormone-receptor complex has now become a (...) that regulates the rate of transcription of that gene.

transcription factor

The posterior lobe (or posterior pituitary) of the hypothalamus is also called the (...).

neurohypophysis

The anterior lobe (or anterior pituitary) of the hypothalamus is also called the (...).

adenohypophysis

The hypothalamus is connected to the pituitary gland by a thin stalk called the (...).

infundibulum

The posterior lobe of the pituitary gland is derived from (...).

neural tissue

What are the two hormones secreted by the posterior pituitary?

1. antidiuretic hormone (ADH)
2. oxytocin

The hormones secreted by the posterior lobe are actually (...); in other words, they are peptides released from neurons.

neuropeptides

Although both posterior pituitary hormones are synthesized in both nuclei, ADH is primarily associated with (...) and oxytocin is primarily associated with (...).

supraoptic nuclei; paraventricular nuclei

Unlike the posterior lobe, which is neural tissue, the anterior lobe is primarily a collection of (...).

endocrine cells

What are the six hormones secreted by the anterior pituitary?

1. thyroid-stimulating hormone (TSH)
2. follicle-stimulating hormone (FSH)
3. luteinizing hormone (LH)
4. growth hormone (GH)
5. prolactin
6. adrenocorticotropic hormone (ACTH)

The hypothalamus and anterior pituitary are linked directly by the (...), which provide most of the blood supply of the anterior lobe.

hypothalamic-hypophysial portal blood vessels

What are the five major endocrine cell types of the anterior pituitary?

1. somatotrophs (20%) secrete GH
2. gonadotrophs (15%) secrete FSH and LH
3. corticotrophs (15%) secrete ACTH
4. lactotrophs (15%) secrete prolactin
5. thyrotrophs (5%) secrete TSH

TSH, FSH, and LH are all (...) consisting of two subunits, α and β.

glycoproteins

The (...) of TSH, FSH, and LH are identical and are synthesized from the same mRNA.

α subunits

The (...) for TSH, FSH, and LH are different and therefore confer the biologic specificity.

β subunits

The placental hormone (...) is structurally related to the TSH-FSH-LH family.

human chorionic gonadotropin (HCG)

The ACTH family of hormones is derived from a single precursor, (...).

pro-opiomelanocortin (POMC)

In (...), POMC and ACTH levels are increased by negative feedback, and because of their MSH activity, skin pigmentation is a symptom of this disorder.

Addison disease (primary adrenal insufficiency)

(...) is secreted throughout life and is the single most important hormone for normal growth to adult stature.

growth hormone

Growth hormone is synthesized in the somatotrophs of the anterior lobe of the pituitary and also is called (...).

somatotropin

Human growth hormone is structurally similar to (...), containing 191 amino acids in a straight-chain polypeptide with 2 internal disulfide bridges.

prolactin

Growth hormone is secreted in a (...) pattern, with bursts of secretion occurring approximately every 2 hours.

pulsatile

At (...), there is an secretory burst of growth hormone, induced in females by estrogen and in males by testosterone.

puberty

(...) and (...) are potent stimuli for growth hormone secretion.

hypoglycemia; starvation

(...) acts directly on somatotrophs of the anterior pituitary to stimulate both synthesis and secretion of growth hormone.

GHRH

(...) is also secreted by the hypothalamus and acts on the somatotrophs to inhibit growth hormone secretion.

somatostatin (SRIF)

Growth hormone secretion is regulated by negative feedback: (1) GHRH is inhibited by (...); (2) growth hormone is inhibited by (...); (3) somatostatin is stimulated by (...).

GHRH (ultra-short loop); somatomedins; growth hormone and somatomedins

The direct actions of growth hormone are mediated by (...) receptors in skeletal muscle, the liver, or adipose tissue.

tyrosine kinase–associated

The indirect actions of growth hormone are mediated through the production of (...) in the liver, the most important of which is (...).

somatomedins (or IGFs); somatomedin C (or IGF-1)

Somatomedins act on target tissues through IGF receptors that are similar to the insulin receptor, having (...) activity.

intrinsic tyrosine kinase

What are the major actions of growth hormone? (3)

1. diabetogenic or anti-insulin effect
2. increased protein synthesis and organ growth
3. increased linear growth

Growth hormone deficiency in children causes (...), including failure to grow, short stature, mild obesity, and delayed puberty.

dwarfism

One variant of dwarfism is (...), in which growth hormone levels are elevated due to a defect in the growth hormone receptors.

Laron dwarfism

Growth hormone excess causes (...) and is most often due to a growth hormone–secreting pituitary adenoma.

acromegaly

Before puberty, excessive levels of growth hormone cause (...) because of intense hormonal stimulation at the epiphyseal plates.

gigantism

Conditions with excess secretion of growth hormone are treated with (...), which inhibit growth hormone secretion by the anterior pituitary.

somatostatin analogues (e.g. octreotide)

(...) is the major hormone responsible for milk production and also participates in the development of the breasts.

prolactin

Chemically, prolactin is related to (...), having 198 amino acids in a single-chain polypeptide with 3 internal disulfide bridges.

growth hormone

In persons who are not pregnant or lactating, prolactin secretion is tonically inhibited by (...) from the hypothalamus.

dopamine (prolactin-inhibiting factor)

Prolactin inhibits its own secretion by increasing the synthesis and secretion of (...) from the hypothalamus.

dopamine

(...) and (...) are the most important stimuli for prolactin secretion.

pregnancy; breast-feeding (suckling)

What are the major actions of prolactin? (3)

1. breast development
2. lactogenesis (milk production)
3. inhibition of ovulation

Prolactin inhibits ovulation by inhibiting the synthesis and release of (...), which accounts for the decreased fertility during breast-feeding.

gonadotropin-releasing hormone (GnRH)

Prolactin deficiency can be caused by total destruction of the (...) or selective destruction of (...).

destruction of the anterior pituitary; lactotrophs

Prolactin excess can be caused by destruction of the (...) or by prolactin- secreting tumors called (...).

destruction of the hypothalamus; prolactinomas

The major symptoms of excess prolactin secretion are (...) and (...).

galactorrhea; infertility

Whether the result of hypothalamic failure or a prolactinoma, prolactin excess can be treated by administration of (...), a dopamine agonist.

bromocriptine

ADH and oxytocin are homologous (...) (containing nine amino acids) synthesized in the supraoptic and paraventricular nuclei of the hypothalamus.

nonapeptides

The ADH neurons have their cell bodies primarily in the (...) nuclei of the hypothalamus.

supraoptic nuclei

The oxytocin neurons have their cell bodies primarily in (...) nuclei of the hypothalamus.

paraventricular

The peptide precursor for ADH is (...), which comprises a signal peptide, ADH, neurophysin II, and a glycoprotein.

prepropressophysin

The precursor for oxytocin is (...), which comprises a signal peptide, oxytocin, and neurophysin I.

prepro-oxyphysin

(...) is the major hormone concerned with regulation of body fluid osmolarity.

ADH (or vasopressin)

(...) is the most important physiologic stimulus for increasing ADH secretion.

increased plasma osmolarity

(...) is a potent stimulus for ADH secretion which overrides plasma osmolarity.

hypovolemia

What are the major actions of ADH? (2)

1. increase in water reabsorption
2. contraction of vascular smooth muscle

The receptor for ADH on the principal cells of the kidney is the (...) receptor, which is coupled to (...) via a G protein.

V₂; adenylyl cyclase

The second messenger for the V₂ receptor is (...), which, via phosphorylation steps, directs the insertion of (...) in the luminal membranes.

cAMP; aquaporin 2 (AQP2)

The receptor for ADH on vascular smooth muscle is the (...) receptor, which is coupled to (...) via a G protein.

V₁; phospholipase C

The second messenger for the V₁ receptor is (...), which produces (...) of vascular smooth muscle.

contraction; IP₃/Ca²⁺

(...) is caused by failure of the posterior pituitary to secrete ADH; the collecting ducts are impermeable to water, and the urine cannot be concentrated.

central diabetes insipidus

Central diabetes insipidus is treated with an ADH analogue, (...).

desmopressin (dDAVP)

In (...), the posterior pituitary is normal but the principal cells of the collecting duct are unresponsive to ADH due to a defect in the V₂ receptor.

nephrogenic diabetes insipidus

Nephrogenic diabetes insipidus is treated with (...).

thiazide diuretics

In (...), excess ADH is secreted from an autonomous site, such as oat cell carcinoma of the lung.

syndrome of inappropriate ADH (SIADH)

SIADH is treated with an ADH antagonist such as (...) or water restriction.

demeclocycline

(...) produces milk “letdown” or milk ejection from the lactating breast.

oxytocin

The major stimulus for oxytocin secretion is (...); however, (...) also cause milk letdown.

suckling; conditioned responses

What are the major actions of oxytocin? (2)

1. milk ejection
2. uterine contraction

Stimulation of powerful rhythmic contractions of uterine smooth muscle by oxytocin is the basis for its use in inducing (...) and in reducing (...).

labor; postpartum bleeding

The two active thyroid hormones are (...) and (...).

triiodothyronine (T₃); thyroxine (T₄)

Thyroid hormones are synthesized by the (...) cells of the thyroid gland.

follicular epithelial cells

The material in the lumen of the follicles is (...), which is composed of newly synthesized thyroid hormones attached to (...).

colloid; thyroglobulin (TG)

(...), a glycoprotein containing large quantities of tyrosine, is synthesized on the rough endoplasmic reticulum and the Golgi apparatus of the thyroid follicular cells.

thyroglobulin (TG)

(...) is actively transported from blood into the thyroid follicular epithelial cells against both chemical and electrical gradients via (...).

I⁻ (iodide); Na⁺-I⁻ cotransport

The anions (...) block Na⁺-I⁻ cotransport into follicular cells and interfere with the synthesis of thyroid hormones.

thiocyanate and perchlorate

Once I⁻ is pumped into the follicular epithelial cell, it is oxidized to (...) by the enzyme (...).

I₂ (iodide); thyroid peroxidase

Thyroid peroxidase is inhibited by (...), which blocks the synthesis of thyroid hormones.

propylthiouracil (PTU)

At the apical membrane, I₂ combines with the (...) moieties of TG, catalyzed by thyroid peroxidase, to form (...) and (...).

tyrosine; monoiodotyrosine (MIT); diiodotyrosine (DIT)

High levels of I⁻ inhibit organification and synthesis of thyroid hormones, which is known as the (...).

Wolff-Chaikoff effect

While still part of TG, coupling reactions occur between MIT and DIT; either two molecules of DIT combine to form (...) or DIT combines with MIT to form (...).

thyroxine (T₄); triiodothyronine (T₃)

Iodinated TG is stored in the follicular lumen as (...) until the thyroid gland is stimulated to secrete its hormones (e.g., by TSH).

colloid

When the thyroid gland is stimulated, iodinated TG is (...) into the follicular epithelial cells.

endocytosed

(...) hydrolyze peptide bonds to release T₄, T₃, MIT, and DIT from TG.

lysosomal proteases

MIT and DIT are deiodinated inside the follicular cell by the enzyme (...), then are incorporated into the synthesis of new TG to begin another cycle.

thyroid deiodinase

Most T₄ and T₃ circulates bound to (...); because only free thyroid hormones are physiologically active, this provides a reservoir of hormones.

thyroxine-binding globulin (TBG)

In (...), blood levels of TBG decrease because there is decreased protein synthesis, resulting in a transient (...) in the level of free thyroid hormones.

hepatic failure; increase

During (...), high levels of estrogen inhibits hepatic breakdown of TBG, resulting in a transient (...) in the level of free thyroid hormones.

pregnancy; decrease

Circulating levels of TBG can be indirectly assessed with the (...), which measures the binding of radioactive T₃ to a synthetic resin.

T₃ resin uptake test

The major secretory product of the thyroid gland is (...), which is the less active form of thyroid hormone.

T₄

In the target tissues, the enzyme (...) converts T₄ to T₃ by removing one atom of I₂ from the outer ring of the molecule.

5′-iodinase

The target tissues also convert a portion of the T₄ to an inactive form, (...), by removing one atom of I₂ from the inner ring of the molecule.

reverse T₃ (rT3)

(...) inhibits 5′-iodinase in tissues such as skeletal muscle, thus lowering O₂ consumption and basal metabolic rate.

starvation

(...) acts on the thyrotrophs of the anterior pituitary to stimulate synthesis and secretion of TSH.

TRH

(...) regulates the growth of the thyroid gland (i.e. a trophic effect) and the secretion of thyroid hormones.

TSH

TSH secretion is regulated by two reciprocal factors: (1) (...) stimulates the secretion of TSH; (2) (...) inhibits the secretion of TSH by down-regulating the TRH receptor.

TRH; thyroid hormone (i.e. free T₃)

The actions of TSH on the thyroid gland are initiated when TSH binds to a membrane receptor, which is coupled to (...) via a G protein.

adenylyl cyclase

Activation of adenylyl cyclase generates (...), which serves as the second messenger for TSH.

cAMP

The TSH receptor on the thyroid cells also is activated by (...), which are antibodies to the TSH receptor.

thyroid-stimulating immunoglobulins

(...), a common form of hyperthyroidism, is caused by increased circulating levels of thyroid-stimulating immunoglobulins.

Graves disease

The first step in the action of thyroid hormones in target tissues is (...).

conversion of T₄ to T₃ by 5′-iodinase

Once T₃ is produced inside the target cells, it binds to a (...).

nuclear receptor

The T3-receptor complex then binds to a (...) on DNA, where it stimulates (...).

thyroid-regulatory element; DNA transcription

A vast array of new proteins are synthesized under the direction of thyroid hormones, including (...).

Na⁺-K⁺ ATPase

What are the major effects of thyroid hormones? (5)

1. increase BMR
2. increase metabolism
3. increase in cardiac output
4. stimulate growth and bone development
5. essential for normal maturation of the CNS

Thyroid hormones increase oxygen consumption in all tissues except (...) by inducing the synthesis and increasing the activity of (...).

brain, gonads, and spleen; Na⁺-K⁺ ATPase

The cardiac effects of thyroid hormones are explained by the fact that they induce the synthesis of (...).

β₁-adrenergic receptors

Many of the effects of thyroid hormones on BMR, heat production, heart rate, and stroke volume are similar to those produced by catecholamines via (...) receptors.

β-adrenergic

The most common form of hyperthyroidism is (...), an autoimmune disorder characterized by increased circulating levels of (...).

Graves disease; thyroid-stimulating immunoglobulins

The diagnosis of hyperthyroidism is based on symptoms and measurement of increased levels of (...).

T₃ and T₄

If the cause of hyperthyroidism is a disorder of the thyroid gland, then TSH levels will be (...).

decreased

If the cause of hyperthyroidism is a disorder of the hypothalamus or anterior pituitary, then TSH levels will be (...).

increased

What are the symptoms of hyperthyroidism? (10)

1. increased basal metabolic rate
2. weight loss
3. negative nitrogen balance
4. increased heat production
5. sweating
6. increased cardiac output
7. dyspnea (shortness of breath)
8. tremor, muscle weakness
9. exophthalmos
10. goiter

Treatment of hyperthyroidism includes (...), which inhibits the synthesis of thyroid hormones, surgical removal of the gland, or radioactive ablation with (...)

propylthiouracil: ¹³¹I⁻

The most common cause of hypothyroidism is (...) in which antibodies may either frankly destroy the gland or block thyroid hormone synthesis.

autoimmune destruction (thyroiditis)

The diagnosis of hypothyroidism is based on symptoms and a finding of decreased levels of (...).

T₃ and T₄

If the cause of hypothyroidism is a disorder of the thyroid gland, then TSH levels will be (...).

increased

If the cause of hypothyroidism is a disorder of the hypothalamus or anterior pituitary, then TSH levels will be (...).

decreased

What are the symptoms of hypothyroidism? (10)

1. decreased basal metabolic rate
2. weight gain
3. positive nitrogen balance
4. decreased heat production
5. cold intolerance
6. decreased cardiac output
7. hypoventilation
8. myxedema
9. drooping eyelids
10. goiter

In some cases of hypothyroidism, (...) develops, in which there is edema due to accumulation of osmotically active mucopolysaccharides in interstitial fluid.

myxedema

When the cause of hypothyroidism is a defect in the thyroid, a (...) develops from the unrelenting stimulation of the thyroid gland by TSH.

goiter

If hypothyroidism occurs in the perinatal period and is untreated, it results in an irreversible form of growth and mental retardation called (...).

cretinism

Treatment of hypothyroidism involves thyroid hormone replacement therapy, usually (...).

T₄ (levothyroxine)

Which of the following conditions are associated with goiter?

1. Graves disease
2. TSH-secreting tumors
3. factitious hyperthyroidism (ingestion of T₄)
4. autoimmune thyroiditis
5. TSH deficiency
6. I⁻ deficiency

1. In Graves disease, high levels of thyroid-stimulating immunoglobulins have a trophic effect on the thyroid gland to produce goiter.
2. In cases of TSH-secreting tumors, increased levels of TSH will have a trophic effect on the thyroid gland to produce goiter.
3. In factitious hyperthyroidism, increased thyroid hormones cause decreased TSH by negative feedback and there is no goiter
4. In autoimmune thyroiditis, decreased thyroid hormones cause increased TSH by negative feedback and produces goiter.
5. In cases of TSH deficiency, decreased levels of TSH cause decreased thyroid hormone secretion and no goiter.
6. In I⁻ deficiency, decreased synthesis of T4 and T3 increases TSH secretion by negative feedback to produce goiter.

The (...), which is in the inner zone of the adrenal gland that comprises 20% of the tissue, is of (...) origin and secretes (...).

adrenal medulla; neuroectodermal; catecholamines

The (...), which is in the outer zone of the adrenal gland that comprises 80% of the tissue, is of (...) origin and secretes (...).

adrenal cortex; mesodermal; adrenocortical steroids

The innermost zone of the adrenal cortex, called the (...), and the middle zone, called the (...), synthesize and secrete (...) and (...).

zona reticularis; zona fasciculata; glucocorticoids; adrenal androgens

The outermost zone of the adrenal cortex, called the (...), secretes (...).

zona glomerulosa; mineralocorticoids

All of the steroids of the adrenal cortex are chemical modifications of a basic steroid nucleus, which is illustrated in the structure of (...).

cholesterol

The (...), represented by cortisol, have a ketone group at carbon 3 (C3) and hydroxyl groups at C11 and C21.

glucocorticoids

The (...), represented by aldosterone, have a double-bond oxygen at C18.

mineralocorticoids

The (...), represented in the adrenal cortex by dehydroepiandrosterone (DHEA) and androstenedione, have a double-bond oxygen at C17.

androgens

The layers of the adrenal cortex are specialized to synthesize and secrete particular steroid hormones; the basis for this is the presence or absence of (...).

enzymes that catalyze modifications of the steroid nucleus

The precursor for all adrenocortical steroids is (...).

cholesterol

The enzymes catalyzing the conversion of cholesterol to active steroid hormones require (...), molecular oxygen, and NADPH.

cytochrome P-450

A flavoprotein enzyme called (...) and an iron-containing protein called (...) are intermediates in the transfer of hydrogen from NADPH to the cytochrome P-450 enzymes.

adrenodoxin reductase; adrenodoxin

The first step in the synthesis of all adrenocortical steroid hormones, conversion of cholesterol to pregnenolone, is catalyzed by (...).

cholesterol desmolase

Cholesterol desmolase, the rate-limiting enzyme in adrenocortical steroid hormone synthesis pathway, is stimulated by (...).

ACTH

The major glucocorticoid produced in humans is (...), which is synthesized in the (...).

cortisol; zonae fasciculata and reticularis

Cortisol is not the only steroid in the pathway with glucocorticoid activity; (...) is also a glucocorticoid.

corticosterone

(...) inhibits 11β-hydroxylase, the last step in cortisol synthesis.

metyrapone

(...) inhibits several steps in the pathway including cholesterol desmolase, the first step.

ketoconazole

(...) are androgenic steroids produced in the (...).

DHEA and androstenedione; zonae fasciculata and reticularis

Adrenal androgens have a ketone group at C17, thus they are also called (...).

17-ketosteroids

The major mineralocorticoid in the body is (...), which is synthesized only in the (...).

aldosterone; zona glomerulosa

The addition of the enzyme (...) in the zona glomerulosa allow the conversion of corticosterone to aldosterone.

aldosterone synthase

Aldosterone is not the only steroid with mineralocorticoid activity; (...) and (...) also have mineralocorticoid activity.

11-deoxycorticosterone (DOC); corticosterone

The synthesis and secretion of steroid hormones by the adrenal cortex depend on the stimulation of cholesterol desmolase by (...).

ACTH

The zonae fasciculata and reticularis, which secrete glucocorticoids and androgens, are under the exclusive control of the (...).

hypothalamic-pituitary axis

The zona glomerulosa, which secretes mineralocorticoids, depends on ACTH for the first step in steroid biosynthesis, but otherwise it is controlled via the (...).

renin-angiotensin-aldosterone system

An impressive feature of the regulation of cortisol secretion is its (...) nature and its (...) pattern.

pulsatile; diurnal (daily)

The secretion of glucocorticoids by the zonae fasciculata/reticularis is regulated exclusively by the (...).

hypothalamic-pituitary axis

(...) acts on the corticotrophs by an adenylyl cyclase/cAMP mechanism to cause secretion of ACTH into the bloodstream.

CRH

(...) activates cholesterol desmolase in the adrenal cortex and up-regulates transcrption of its own receptor.

ACTH

ACTH has a (...) secretory pattern that drives a parallel pattern of cortisol secretion.

pulsatile and diurnal

Negative feedback is exerted by cortisol at three points in the hypothalamic-pituitary axis: (1) it directly inhibits (...); (2) it indirectly inhibits CRH secretion by effects on (...); (3) it inhibits the action of CRH on the (...).

CRH secretion; hippocampal neurons; anterior pituitary

The (...) test is based on the negative feedback effects of cortisol on the CRH-ACTH axis.

dexamethasone suppression

When a low dose of dexamethasone is given to a healthy person, it inhibits (...).

ACTH secretion

The major use of the dexamethasone suppression test is in persons with (...).

hypercortisolism

If the cause of hypercortisolism is (...), a low dose of dexamethasone does not suppress cortisol secretion but a high dose of dexamethasone does.

ACTH-secreting tumor

If the cause of hypercortisolism is an (...), then neither low-dose nor high-dose dexamethasone suppresses cortisol secretion.

adrenal cortical tumor

The major con­trol of aldosterone secretion is via the (...).

renin–angiotensin II–aldosterone system

The mediator of mineralcorticoid secretion is (...), which increases the synthesis and secretion of aldosterone by stimulating cholesterol desmolase and aldosterone synthase.

angiotensin II

(...) is the enzyme that catalyzes the conversion of angiotensinogen to angiotensin I, which is inactive.

renin

(...) catalyzes the conversion of angiotensin I to angiotensin II, which then acts on the zona glomerulosa to stimulate aldosterone synthesis.

angiotensin-converting enzyme (ACE)

Increases in serum (...) concentration increase aldosterone secretion.

K⁺

What are the major actions of glucocorticoids? (7)

1. stimulation of gluconeogenesis
2. anti-inflammatory effects
3. suppression of immune response
4. maintain vascular responsiveness to catecholamines
5. inhibition of bone formation
6. increases in glomerular filtration rate (GFR)
7. effects on CNS (e.g decreased REM sleep)

Glucocorticoids are essential for survival during (...) because they stimulate these gluconeogenic routes.

fasting

Cortisol interferes with the body's inflammatory response by (1) inducing synthesis of (...), an inhibitor of phospholipase A₂; (2) inhibiting production of (...), and proliferation of T lymphocytes; and (3) inhibiting release of (...) and (...) from mast cells and platelets.

lipocortin; interleukin-2 (IL-2); histamine; serotonin

Aldosterone has three actions on the late distal tubule and collecting ducts:

1. It increases (...) reabsorption.
2. It increases (...) secretion.
3. It increases (...) secretion.

Na⁺; K⁺; H⁺

Renal cells contain the enzyme (...), which converts high-affinity cortisol to low affinity cortisone to prevent it from dominating mineralocorticoid receptors.

11β-hydroxysteroid dehydrogenase

In (...), there is increased synthesis of adrenal androgens leading to masculinization in females and suppression of gonadal function in both males and females.

adrenogenital syndrome

In the adrenogenital syndromes, due to the overproduction of adrenal androgens, there will be increased urinary levels of (...).

17-ketosteroids

Cortisol promotes gluconeogenesis; therefore, excess levels produce (...) and deficits produce (...) upon fasting.

hyperglycemia; hypoglycemia

Aldosterone causes increased K⁺ secretion by the renal principal cells; thus excess causes (...) and deficiency causes (...).

hypokalemia; hyperkalemia

Because adrenal androgens have testosterone-like effects, in females, overproduction causes (...) and deficits result in (...).

masculinization; loss of pubic hair and libido

(...) is commonly caused by autoimmune destruction of all zones of the adrenal cortex, resulting in decreased synthesis of all adrenocortical hormones.

Addison disease (primary adrenocortical insufficiency)

Addison disease also is characterized by (...), particularly of the elbows, knees, nail beds, nipples, and areolae and on recent scars.

hyperpigmentation

Hyperpigmentation in Addison disease is a result of increased levels of (...).

ACTH (contains the α-MSH fragment)

Conditions of (...) occur when there is insufficient CRH or insufficient ACTH.

secondary adrenocortical insufficiency

(...) is the result of chronic excess of glucocorticoids due to overproduction by the adrenal cortex or exogenous administration.

Cushing syndrome

(...) is characterized by excess glucocorticoids, in which the cause is hypersecretion of ACTH from a pituitary adenoma.

Cushing disease

What are the symptoms of Cushing syndrome? (8)

1. hyperglycemia
2. muscle wasting (increased proteolysis)
3. increased lipolysis and thin extremities
4. central obesity, round face, buffalo hump
5. poor wound healing
6. osteoporosis, and
7. striae (caused by a loss of connective tissue)
8. virilization and menstrual disorders in females

The (...), in which a synthetic glucocorticoid is administered, can distinguish between Cushing syndrome and Cushing disease.

dexamethasone suppression test

In (...), because the tumor functions autonomously, cortisol secretion is not suppressed by either low- or high-dose dexamethasone.

Cushing syndrome

In (...), ACTH and cortisol secretion are suppressed by high-dose dexamethasone but not by low-dose dexamethasone.

Cushing disease

Treatment of Cushing syndrome includes administration of drugs such as (...), which block steroid hormone biosynthesis.

ketoconazole or metyrapone

Because of its different etiology, treatment of Cushing disease involves (...).

surgical removal of the ACTH-secreting tumor

(...) is caused by an aldosterone-secreting tumor.

Conn syndrome (primary hyperaldosteronism)

Treatment of Conn syndrome consists of administration of an aldosterone antagonist such as (...), followed by surgical removal of the tumor.

spironolactone

The most common enzymatic defect in the steroid hormone biosynthetic pathways is deficiency of (...), which belongs to a group of disorders called (...).

21β-hydroxylase; adrenogenital syndrome

Without 21β-hydroxylase, the adrenal cortex is unable to convert progesterone to (...) or 17-hydroxyprogesterone to (...).

DOC; 11-deoxycortisol (the adrenal cortex does not synthesize mineralocorticoids or glucocorticoids)

In 21β-hydroxylase deficiency, steroid intermediates will accumulate above the enzyme block and be shunted toward production of (...).

adrenal androgens (causes virilization in females)

In 21β-hydroxylase deficiency, elevated ACTH (via negative feedback) has a trophic effect on the adrenal cortex; thus the other name for this disorder is (...).

congenital adrenal hyperplasia

A less common congenital abnormality of the steroid hormone biosynthetic pathway is deficiency of (...).

17α-hydroxylase

Without 17α-hydroxylase, pregnenolone cannot be converted to (...) and progesterone cannot be converted to (...).

17-hydroxypreg­nenolone; 17-hydroxyprogesterone (neither gluco­corticoids nor adrenal androgens will be produced)

In this 17α-hydroxylase deficiency, steroid intermediates accumulate to the left of the enzyme block and will be shunted toward production of (...).

mineralocorticoids (causes hypertension, hypokalemia, and metabolic alkalosis)

The endocrine cells of the pancreas are arranged in clusters called the (...), which compose 1% to 2% of the pancreatic mass.

islets of Langerhans

The β cells compose 65% of the islet and secrete (...).

insulin

The α cells compose 20% of the islet and secrete (...).

glucagon

The delta (δ) cells compose 10% of the islet and secrete (...).

somatostatin

The remaining cells of the pancreatic islets secrete (...).

pancreatic polypeptide

Insulin is synthesized and secreted by the (...).

β cells

Insulin is a peptide hormone consisting of two straight chains designated as the (...) and (...).

A chain; B chain

The synthesis of insulin is directed by a gene on (...), a member of a superfamily of genes that encode related growth factors.

chromosome 11

The mRNA directs ribosomal synthesis of (...), which contains four peptides: a signal peptide, the A and B chains of insulin, and a connecting peptide (C peptide).

preproinsulin

The signal peptide is cleaved from preproinsulin early in the biosynthetic process, yielding (...)

proinsulin

Proinsulin is packaged in secretory granules on the Golgi apparatus, during which, proteases cleave the connecting peptide, yielding (...).

insulin

The secretion of (...) is the basis of a test for β cell function in persons with type I diabetes mellitus who are receiving injections of exogenous insulin.

C peptide (It is packaged with insulin and released in equimolar quantities)

The most important factor influencing the secretion of insulin by β cells is (...)

glucose

The β cell membrane contains (...), a specific transporter for glucose that moves glucose from the blood into the cell by facilitated diffusion

GLUT2

Once inside the cell, glucose is phosphorylated to glucose-6-phosphate by (...), and glucose-6-phosphate is subsequently oxidized.

glucokinase

Oxidation of glucose-6-phosphate generates (...), which appears to be the key factor that regulates insulin secretion.

ATP

When ATP levels inside the β cell increase, the ATP-sensitive (...) channels close, which depolarizes the β cell membrane.

K⁺

The depolarization of the β cell caused by closure of the K⁺ channels opens voltage-sensitive (...) channels.

Ca²⁺

Increases in intracellular Ca²⁺ concentration within the β cell causes exocytosis of the (...)-containing secretory granules

insulin

Oral glucose is a more powerful stimulant for insulin secretion than intravenous glucose because it stimulates the secretion of (...).

glucose-dependent insulinotropic peptide (GIP)

(...) activates a G_q protein coupled to phospholipase C, which leads to a rise in intracellular Ca²⁺, causing exocytosis of insulin.

glucagon

(...) inhibits the insulin-releasing mechanism that glucagon stimulates.

somatostatin

(...) treat type II diabetes mellitus by stimulating insulin release from β cells by closing the ATP-dependent K⁺ channels.

sulfonylureas (e.g. tolbutamide, glyburide)

The insulin receptor is a tetramer composed of two (...) and two (...), joined by disulfide bonds.

α subunits; β subunits

The (...) of the insulin receptor have intrinsic tyrosine kinase activity.

β subunits

Insulin binds to the (...) of the tetrameric insulin receptor, producing a conformational change in the receptor.

α subunits

The conformational change in the α subunits of the insulin receptor activates tyrosine kinase in the β subunits, which (...) presence of ATP.

autophosphorylate

Activated (...) on the β subunits phosphorylates several other proteins or enzymes that are involved in the physiologic actions of insulin.

tyrosine kinase

Insulin (...) its own receptor by decreasing the rate of synthesis and increasing the rate of degradation of the receptor.

down-regulates

What are the major actions of insulin? (4)

1. decreases blood glucose concentration
2. decreases blood fatty acid and ketoacid concentrations
3. decreases blood amino acid concentration
4. promotes K⁺ uptake into cells by stimulating Na⁺-K⁺ ATPase

The hypoglycemic action of insulin is the result of (1) it increasing glucose transport into target cells by increasing (...) (2) it promoting (...) in the liver and in muscle and inhibiting (...); (3) it inhibiting gluconeogenesis by increasing the production of (...).

GLUT4; glycogenesis; glycogenolysis; fructose 2,6-bisphosphate

Insulin also appears to have a direct effect on the hypothalamic (...) center independent of the changes it produces in blood glucose concentration.

satiety

(...) is caused by destruction of β cells, often as a result of an autoimmune process.

type I (insulin-dependent) diabetes mellitus

The increased levels of ketoacids in type I diabetes mellitus cause a form of metabolic acidosis called (...).

diabetic ketoacidosis (DKA)

In diabetes mellitus, the nonreabsorbed glucose in the renal tubules acts as an osmotic solute in urine, producing (...).

osmotic diuresis

(...) is often associated with obesity and is caused by down-regulation of insulin receptors in target tissues and insulin resistance.

type II (non–insulin-dependent) diabetes mellitus

(...) can be used to treat type II diabetes mellitus by stimulating pancreatic insulin secretion, while (...) up-regulate insulin receptors on target tissues.

sulfonylureas (e.g. tolbutamide or glyburide); biguanides (e.g. metformin)

Glucagon is synthesized and secreted by the (...) of the islets of Langerhans.

α cells

The major factor stimulating the secretion of glucagon is (...).

decreased blood glucose concentration

Glucagon secretion also is stimulated by the ingestion of protein, specifically by the amino acids (...) and (...).

arginine; alanine

Another factor stimulating glucagon secretion is (...), which is secreted from the gastrointestinal tract when protein or fat is ingested.

cholecystokinin (CCK)

The glucagon receptor is coupled to (...) via a G protein and second messenger is (...).

adenylyl cyclase; cAMP

What are the major actions of glucagon? (2)

1. increases blood glucose concentration
2. increases blood fatty acid and ketoacid concentrations

Glucagon increases the blood glucose concentration by (1) stimulating (...) and inhibiting (...); and (2) by increasing gluconeogenesis by decreasing the production of (...).

glycogenolysis; glycogenesis; fructose 2,6-bisphosphate

Pancreatic somatostatin is secreted by the (...) of the islets of Langerhans.

δ cells

Pancreatic somatostatin inhibits secretion of (...) via paracrine actions.

insulin and glucagon

The total Ca²⁺ concentration in blood is normally 10 mg/dL; (...) amounts to 50% of total Ca²⁺ and it is the only form that is biologically active.

free, ionized Ca²⁺

(...) is a decrease in the plasma Ca²⁺ concentration, which produces symptoms of hyperreflexia, spontaneous twitching, muscle cramps, and tingling and numbness.

hypocalcemia

Specific indicators of hypocalcemia include the (...), or twitching of the facial muscles elicited by tapping on the facial nerve, and the (...), which is carpopedal spasm upon inflation of a blood pressure cuff.

Chvostek sign; Trousseau sign

(...) is an increase in the plasma Ca²⁺ concentration, which produces symptoms of constipation, polyuria, polydipsia, hyporeflexia, lethargy, coma, and death.

hypercalcemia

Changes in plasma (...) concentration alter the total Ca²⁺ concentration in the same direction.

protein

Changes in plasma (...) concentration alter the ionized Ca²⁺ concentration by changing the fraction of complexed Ca²⁺.

anion

(...) abnormalities alter the ionized Ca²⁺ concentration by changing the fraction of Ca²⁺ bound to plasma albumin.

acid-base

In (...), there is more H⁺ in blood to bind to albumin, leaving fewer sites for Ca²⁺ to bind, thus the free ionized Ca²⁺ concentration (...).

acidemia; increases

In (...), there is less H⁺ in blood to bind to albumin, leaving more sites for Ca²⁺ to bind, thus the free ionized Ca²⁺ concentration (...).

alkalemia; decreases

What three organ systems are involved in Ca²⁺ homeostasis?

bone, kidney, and intestine

The (...) of the parathyroid glands synthesize and secrete PTH.

chief cells

PTH secretion is regulated by plasma (...) concentration; when it decreases to less than (...), PTH secretion is stimulated.

Ca²⁺; 10 mg/dL

The parathyroid cell membrane contains (...) that are linked, via a G protein to phospholipase C.

Ca²⁺ sensing receptors

Chronic (...) causes (...), which is characterized by increased synthesis and storage of PTH and hyperplasia of the parathyroid glands.

hypocalcemia; secondary hyperparathyroidism

Chronic (...) causes decreased synthesis and storage of PTH, increased breakdown of stored PTH, and release of inactive PTH fragments into the circulation.

hypercalcemia

(...) has parallel, although less important, effects on PTH secretion as Ca²⁺.

Mg²⁺

The receptor for PTH is coupled, via a G protein, to (...).

adenylyl cyclase

In bone, PTH receptors are located only on (...).

osteoblasts

Initially and transiently, PTH causes (...) by a direct action on osteoblasts.

increased bone formation

In a second, long-lasting, indirect action on osteoclasts, PTH causes (...), mediated by (...) released from osteoblasts.

increased bone resorption; cytokines

PTH inhibits (...) reabsorption in the proximal convoluted tubule.

phosphate (causes phosphaturia)

The cAMP generated in cells of the proximal tubule is excreted in urine and is called (...).

nephrogenous or urinary cAMP

The phosphaturic action of PTH is critical because otherwise the phosphate resorbed from bone would (...).

complex Ca²⁺ in ECF

PTH stimulates (...) reabsorption in the proximal convoluted tubule.

Ca²⁺

PTH does not have direct actions on the small intestine, although indirectly it stimulates intestinal Ca²⁺ absorption via (...).

activation of vitamin D

Primary hyperparathyroidism is most commonly caused by (...).

parathyroid adenomas (tumors)

In primary hyperparathyroidism, (...) results from increased bone re­­sorption, increased renal Ca²⁺ reabsorption, and increased intestinal Ca²⁺ absorption.

hypercalcemia

In primary hyperparathyroidism, (...) results from decreased renal phosphate reabsorption and phosphaturia.

hypophosphatemia

Persons with primary hyperparathyroidism are said to have "(...)."

“stones, bones, and groans” (stones from hypercalciuria, bones from increased bone resorption, and groans from constipation)

In secondary hyperparathyroidism, the parathyroid glands are stimulated to secrete excessive PTH secondary to (...), which can be caused by (...).

hypocalcemia; vitamin D deficiency or chronic renal failure

(...) is a relatively common, inadvertent consequence of thyroid surgery or parathyroid surgery.

hypoparathyroidism

In hypoparathyroidism, (...) results from decreased bone resorption, decreased renal Ca²⁺ reabsorption, and decreased intestinal Ca²⁺ absorption.

hypocalcemia

In hypoparathyroidism, (...) results from increased phosphate reabsorption.

hyperphosphatemia

Patients with (...) have hypocalcemia and hyperphosphatemia; however, circulating levels of PTH are increased rather than decreased.

pseudohypoparathyroidism

Pseudohypoparathyroidism is an inherited autosomal dominant disorder in which the (...) for PTH in kidney and bone is defective.

G_s protein

Some malignant tumors secrete (...), which is structurally homologous with the PTH secreted by the parathyroid glands, with all the same physiologic actions.

PTH-related peptide (PTH-rp)

Humoral hypercalcemia of malignancy is treated with (...), which inhibits renal Ca²⁺ reabsorption, and inhibitors of bone resorption such as (...).

furosemide; etidronate

(...) is an autosomal dominant disorder characterized by decreased urinary Ca²⁺ excretion and increased serum Ca²⁺ concentration.

familial hypocalciuric hypercalcemia (FHH)

FHH is caused by inactivating mutations of (...) in the parathyroid glands and the thick, ascending limb of the kidney.

Ca²⁺ sensing receptors

Calcitonin is synthesized and secreted by the (...) of the thyroid gland.

parafollicular or C cells

The major stimulus for calcitonin secretion is (...).

increased plasma Ca²⁺ concentration

The major action of calcitonin is to (...), which decreases the plasma Ca²⁺ concentration.

inhibit bone resorption

(...) in conjunction with PTH, is the second major regulatory hormone for Ca²⁺ and phosphate metabolism.

vitamin D

Vitamin D in the form of (...) is provided in the diet and is produced in the skin from cholesterol.

cholecalciferol

Cholecalciferol is physiologically inactive; it is hydroxylated in the liver to form (...), which also is inactive.

25-hydroxycholecalciferol

In the kidney, 25-hydroxycholecalciferol (1) can be hydroxylated at C1 to produce (...), the active form, or (2) can be hydroxylated at C24 to produce (...), which is inactive.

1,25-dihydroxycholecalciferol; 24,25-dihydroxycholecalciferol

C1 hydroxylation of 25-hydroxycholecalciferol in the kidney is catalyzed by the enzyme (...).

1α-hydroxylase

1α-hydroxylase activity is stimulated by(1) decreased plasma (...) concentration, (2) increased circulating levels of (...), and (3) decreased plasma (...) concentration.

Ca²⁺; PTH; phosphate

The overall role of 1,25-dihydroxycholecalciferol is to increase the plasma concentration of (...) to promote (...).

Ca²⁺ and phosphate; mineralization of new bone

In the intestine, 1,25-dihydroxycholecalciferol induces the synthesis of a vitamin D–dependent Ca2+-binding protein called (...).

calbindin D-28K

The actions of 1,25-dihydroxycholecalciferol on the kidney are parallel to its actions on the intestine—it stimulates (...).

Ca²⁺ and phosphate reabsorption

In bone, 1,25-dihydroxycholecalciferol acts synergistically with PTH to stimulate (...).

bone resorption (“old” bone is resorbed to provide Ca²⁺ and phosphate so that “new” bone can be mineralized)

In children, vitamin D deficiency causes (...), a condition in which insufficient amounts of Ca²⁺ and phosphate are available to mineralize the growing bones.

rickets

In adults, vitamin D deficiency results in (...), in which new bone fails to mineralize, resulting in bending and softening of the weight-bearing bones.

osteomalacia

(...) occurs when the kidney is unable to produce the active metabolite, 1,25-dihydroxycholecalciferol.

vitamin D resistance

Vitamin D resistance can be caused by the congenital absence of 1α-hydroxylase or, more commonly, by (...).

chronic renal failure