A&P Ch. 17A (Finished)
What is the main difference between the endocrine system & the nervous system?
- The nervous system uses 2 forms of intercellular communication → electrical & chemical signaling
- The endocrine system only uses chemical signaling.. which takes FAR longer
- However, the nervous system can cause rapid endocrine responses to keep up with sudden changes
What does the endocrine system consist of?
- Cells, tissues & organs that secrete hormones as primary or secondary function
- Includes pituitary, thyroid, parathyroid, adrenal & pineal glands despite some of these glands serving both endocrine & non-endocrine functions
Whats the function of endocrine glands?
- Secrete their hormones directly into surrounding fluid → interstitial fluid & blood vessels transport hormones throughout body
What is the exocrine system?
- USES DUCTS
- System of hormones & glands, where glands secrete straight to target site via ducts
- Takes place within same cell
- Chemical that elicits a response in same cell that secreted it
Local intercellular communication is the province of..
- Paracrine (paracrine factor)
- Chemical that induces response in neighboring cells.
- Concentration generally too low to elicit response from distant tissues
On the basis of their chemical structure, how many groups can hormones of the body be divided into?
- Amino acid derived → include amines, peptides & proteins
- Lipid derived → Includes steroids
- Each group affects hormone’s distribution, type of receptors it binds to & other aspects of its function
What are hormones derived from the modification of amino acids called?
- Amine hormones
- A -COOH (carboxyl group) is removed
- -NH+3 (amine group)
What amino acids are amine hormones synthesized from?
- Tryptophan or
- Derived from a single amino acid ONLY
What is an example of a hormone derived from tryptophan?
- Melatonin → secreted by pineal gland → helps regulate circadian rhythm
What are some hormones synthesized from tyrosine derivatives?
- Metabolism-regulating thyroid hormones
- Catecholamines → epinephrine, norepinephrine & dopamine
Epinephrine & norepinephrine are secreted by...
- The adrenal medulla → plays role in fight-or-flight response
Dopamine is secreted by the..
- Hypothalamus → inhibits release of certain anterior pituitary hormones
What do peptide & protein hormones consist of?
- Multiple amino acids that link to form an amino acid chain
What do peptide hormones consist of?
- Short chains of amino acids
- Ex: antidiuretic hormone (ADH) → pituitary hormone important in fluid balance & atrial-natriuretic peptide (produced by heart, helps to ↓ blood pressure)
What do protein hormones consist of?
- Longer chains of amino acids (polypeptides)
- Ex: growth hormone → produced by pituitary gland
- Ex: follicle-stimulating hormone (FSH) → which has an attached carbohydrate group → thus classified as glycoprotein.
What do peptide & protein hormones have in common?
- Both types are synthesized like other body proteins:
- DNA transcribed → mRNA translated → an amino acid chain
What are steroid hormones derived from?
- Lipid cholesterol
What are 2 examples of steroid hormones?
- Testosterone & estrogens → both produced by gonads
What is the 1/2 life of a hormone?
(Definition only, don't worry)
- Time required for 1/2 the concentration of the hormone to be degraded
Why are the 1/2 lives of lipid derived hormones much longer than amino acid derived hormones?
- Like cholesterol, steroid hormones are hydrophobic
- B/c blood is water-based → these hormones must travel to their target cell bound to a transport protein
What receives the "message" a hormone sends?
- Hormone receptors → these proteins are located either inside cell or within cell mb
How do hormone receptors process the "message" a hormone sends?
- By recognizing ONLY specific molecule shapes & side groups → initiates other signaling events or cellular mechanisms accordingly to that
The response triggered by a hormone depends on which 2 major variables?
- Structure/ Type of hormone
- Target cell
What are some actions or responses that can occur once a target cell receives a signal?
- Protein synthesis
- Activation or deactivation of enzymes
- Alterations to cell mb permeability
- Mitosis & cell growth
- Further secretions of products
Where are intracellular hormone receptors located?
- Inside the cell
How does the binding of steroid hormones work?
- Binds to its receptor within cytosol or within nucleus → generates hormone-receptor complex → moves toward chromatin in nucleus of cell → binds to particular segment of DNA
How does the binding of thyroid hormones work in contrast to steroid hormones?
- Binds to receptors already bound to DNA
What do steroid & thyroid hormones have in common?
- Both generate hormone-receptor complex with DNA → triggers transcription of target gene to mRNA → moves to cytosol → directs protein synthesis by ribosomes
Hormones that are hydrophilic are unable to diffuse through lipid bilayer of cell mb, what must they do instead?
- Pass their "message" on to a receptor located on extracellular surface of cell mb
Except for thyroid hormones, all amino acid derived hormones must rely in receptors located on extracellular surface of cell mb only to pass their message on. What's the significance of that?
- They DO NOT affect transcription of target genes
- Initiates signal cascade
When a signal cascade is initiated by amino acid derived hormones, what serves as the 1st messenger?
- The hormone
When a signal cascade is initiated by the 1st messenger, what acts as the 2nd messenger?
- Most hormones use cyclic adenosine monophosphate (cAMP)
What is the 1st step of the cAMP second messenger system?
- H2O soluble (hydrophilic hormone) binds to its receptor in cell MB
What is the 2nd step of the cAMP second messenger system?
- Receptor in cell mb is associated with intracellular component (G protein)
- Binding of hormone to G- protein → activates G-protein
What is the 3rd step of the cAMP second messenger system?
- The activated G protein in turn activates enzyme adenylyl cyclase (or adenylate cyclase)
What is the 4th step of the cAMP second messenger system?
- Adenylyl cyclase converts adenosine triphosphate (ATP) → cAMP
What is the 5th step of the cAMP second messenger system?
- cAMP activates protein kinase, which is present in cytosol of cell
What is the 6th step of the cAMP second messenger system?
- Activated protein kinases initiate a phosphorylation cascade
- Multiple protein kinases phosphorylate (add a phosphate group to) numerous & various cellular proteins, including other enzymes
How does phosphorylation of cellular proteins vary?
- Effects vary according to type of target cell, G proteins and kinases involved & phosphorylation of proteins → Anywhere from nutrient metabolism to synthesis of different hormones and other products can happen
What are 3 hormones that use cAMP as a second messenger?
- Calcitonin → Important for bone construction & regulating blood calcium levels
- Glucagon → plays a role in blood glucose levels
- Thyroid-stimulating hormone (TSH) → causes release of T3 & T4 from thyroid gland
What are the main effects of the phosphorylation cascade?
- ↑ efficiency, speed & ↑ specificity of hormonal response, as thousands of signaling events can be initiated simultaneously in response to very ↓ concentration of hormone in bloodstream.
- However, duration of hormone signal is short
What enzyme deactivates cAMP?
- Phosphodiesterase (PDE), located in cytosol
- PDE helps to ensure that target cell’s response ceases quickly unless new hormones arrive at cell mb
There are also G proteins that decrease the levels of cAMP in the cell in response to hormone binding. What is an example of this?
- When growth hormone–inhibiting hormone (GHIH) (somatostatin) → binds to its receptors in pituitary gland → level of cAMP ↓ → thus inhibiting secretion of human growth hormone
Not all water-soluble hormones initiate the cAMP second messenger system. One common alternative system exists for those that don't, what does it use?
- Ca2+ ions function as second messenger.
- In this system, G proteins activate enzyme phospholipase C (PLC) which functions similarly to adenylyl cyclase.
Once activated, what does phospholipase C (PLC) cleave?
- A membrane-bound phospholipid into 2 molecules → diacylglycerol (DAG) & inositol triphosphate (IP3)
Much like cAMP, what does diacylglycerol (DAG) do?
- Activates protein kinases that initiate a phosphorylation cascade.
What does inositol triphosphate (IP3) do?
- Causes Ca2+ ions to be released from storage sites within cytosol, such as from within smooth endoplasmic reticulum (SER).
Once Ca2+ ions are released from storage sites within cytosol, like the SER.. what do they act as?
- Act as second messengers in 2 ways:
- They can influence enzymatic & other cellular activities directly
- They can bind to calcium-binding proteins, most common of which is calmodulin.
Upon binding calcium, calmodulin is able to modulate which enzyme within the cell?
- Protein kinase
What are some examples of hormones that use Ca2+ ions as a second messenger system?
- Angiotensin II → helps regulate blood pressure through vasoconstriction
- Growth hormone–releasing hormone (GHRH) → causes pituitary gland to release growth hormones
What is the process of downregulation?
- When theres ↑ level of a hormone circulating in bloodstream → can cause its target cells to ↓ their # of receptors for that hormone
What is the process of upregulation?
- When level of a hormone is chronically ↓ → target cells engage in this process to ↑ their # of receptors.
- This process allows cells to ↑ sensitivity to hormone that is present
What are the 3 most common types of hormone interactions?
- Permissive effect
- Synergistic effect
- Antagonistic effect
What is the permissive effect?
- When presence of 1 hormone enables another hormone to act
What is the synergistic effect?
- When 2 hormones with similar effects produce an amplified response
What is the antagonistic effect?
- When 2 hormones have opposing effects
- Such as relationship between insulin & glucagon
What is a positive feedback loop?
- Intensifies response until end point is reached
What is a negative feedback loop?
- Inhibition of further secretion of a hormone in response to adequate levels of such hormone.
- This allows blood levels of hormone to be regulated within extremely narrow range
What controls endocrine activity?
- Reflexes triggered by both chemical & neural stimuli
- Reflexes may be simple, involving only 1 hormone response,
- Reflexes may be more complex & involve many hormones, an example being hypothalamic control of various anterior pituitary–controlled hormones.
What are humoral stimuli?
- Changes in blood levels of non-hormone chemicals, such as nutrients or ions → release or inhibition of hormone → maintain homeostasis
What is the "command center" of the endocrine system?
- The hypothalamus–pituitary complex
What does the hypothalamus-pituitary complex do?
- Coordinates messages of endocrine & nervous systems.
- Secretes several hormones that directly produce responses in target tissues
- Secretes hormones that regulate synthesis & secretion of hormones of other glands
What is the hypothalamus?
- Structure of diencephalon of brain located anterior & inferior to thalamus
What is the function of the hypothalamus?
- Both neural & endocrine functions
- Produces & secretes many hormones
- Anatomically & functionally related to pituitary gland (or hypophysis)
What is the hypophysis suspended from?
- Stem called infundibulum (or pituitary stalk)
What is the pituitary gland cradled within?
- Sellaturcica of sphenoid bone of skull
What does the hypophysis consist of?
- 2 lobes that arise from distinct parts of embryonic tissue
- Posterior pituitary (or neurohypophysis) is neural tissue
- Anterior pituitary (or adenohypophysis) is glandular tissue that develops from primitive digestive tract
- The posterior pituitary gland
- Actually an extension of neurons of paraventricular & supraoptic nuclei of hypothalamus → cell bodies of these regions rest in hypothalamus → Their axons descend as hypothalamic–hypophyseal tract within infundibulum → ends in axon terminals that comprise posterior pituitary
Does the neurohypophysis produce hormones?
- Stores & secretes hormones produced by:
- Paraventricular nuclei → produces hormone oxytocin
- Supraoptic nuclei → produces ADH (vasopressin)
- The anterior pituitary gland
- Produces & secretes several peptide hormones that regulate many physiological processes including growth, stress & reproduction
What are the functions of oxytocin?
- Prompts uterine contractions that push fetal head toward cervix.
- Necessary for milk ejection reflex (commonly referred to as “let-down”)
- Parent–newborn bonding (attachment)
- Thought to be involved in feelings of love & closeness, as well as in sexual response
What are osmoreceptors?
- Specialized cells within hypothalamus that are particularly sensitive to concentration of sodium ions & other solutes.
In response to ↑ blood osmolarity, (can occur during dehydration or following very salty meal) the osmoreceptors signal the posterior pituitary to release antidiuretic hormone (ADH). Where are the target cells of ADH located and what are its effects?
- Tubular cells of kidneys.
- It ↑ epithelial permeability to H2O = ↑ H2O reabsorption
- ↑ H2O reabsorbed from filtrate = ↑ amount of H2O returned to blood & ↓ less excreted in urine → so.. ↑ H2O concentration results in ↓ concentration of solutes (like Na+)
Why is ADH also called vasopressin?
- In ↑↑ concentrations → constriction of blood vessels → which ↑ peripheral resistance → thus ↑ blood pressure
What is the release of ADH controlled by?
- Negative feedback loop.
- As blood osmolarity ↓ → hypothalamic osmoreceptors sense change → prompts corresponding ↓ in secretion of ADH → Thus ↓ H2O is reabsorbed from urine filtrate
How does alcohol affect the secretion of ADH?
- Inhibits release of ADH → resulting in ↑ urine production → eventually leading to dehydration → hangover :/
What is diabetes insipidus caused by?
- chronic underproduction of ADH → results in chronic dehydration.
Patients with diabetes insipidus feel thirsty and increase their consumption of fluids, this will not decrease the solute concentration in their blood, why??
- ADH levels are not ↑ enough to trigger H2O reabsorption in kidneys → electrolyte imbalances can occur in severe cases
What does the adenohypophysis originate from?
- Digestive tract in embryo & migrates toward brain during fetal development.
What are the 3 regions of the adenohypophysis?
- Pars distalis → most anterior
- Pars intermedia → adjacent to posterior pituitary
- Tuberalis → slender “tube” that wraps infundibulum
What is the secretion of hormones from the anterior pituitary regulated by?
- 2 classes of hormones;
- Releasing hormones → secreted by hypothalamus → stimulate secretion of hormones from anterior pituitary
- Inhibiting hormones → inhibit secretion
Within infundibulum, a bridge of capillaries that connects the hypothalamus to the adenohypophysis. What is this called?
- The hypophyseal portal system → allows hypothalamic hormones to transported to adenohypophysis without first entering systemic circulation
What does the hypophyseal portal system originate from?
- Superior hypophyseal artery → branches off the carotid arteries & transports blood to hypothalamus
- The branches of superior hypophyseal artery form hypophyseal portal system
How do hypothalamic releasing & inhibiting hormones travel?
- Through primary capillary plexus → portal veins which carry the hormones → adenohypophysis → hormones produced by adenohypophysis (in response to releasing hormone) → secondary capillary plexus → then drain into circulation
How many hormones does the adenohypophysis produce?
- Adrenocorticotropic hormone (ACTH)
- Follicle-stimulating hormone (FSH)
- Growth hormone (GH)
- Luteinizing hormone (LH)
- Thyroid-stimulating hormone (TSH)
What composes the tropic hormones and why are they called that?
(trope- = “turning”)
- B/c they turn on or off function of other endocrine glands
- Adrenocorticotropic hormone (ACTH)
- Follicle-stimulating hormone (FSH)
- Luteinizing hormone (LH)
- Thyroid-stimulating hormone (TSH)
The endocrine system regulates the growth of the human body, protein synthesis, and cellular replication. What's the major hormone involved in this process?
- Growth hormone (GH) (or somatotropin) → a protein hormone produced & secreted by adenohypophysis
What is the main function of growth hormone (GH)?
- Anabolic → promotes protein synthesis & tissue building through direct & indirect mechanisms.
How are GH levels controlled?
- By release of GHRH & GHIH (also known as somatostatin) from hypothalamus.
When does a glucose-sparing effect occur?
- When GH stimulates lipolysis (breakdown of adipose tissue) → releases fatty acids into blood → many tissues switch from glucose to fatty acids as main energy source → which obviously means that ↓ glucose is taken up from bloodstream.
How does GH initiate a "diabetogenic" effect?
- GH stimulates liver to break down glycogen to glucose → then deposited into blood → ➚ blood glucose levels
What does the term "diabetogenic” mean?
- It's derived from similarity in ↑ blood glucose levels observed between individuals with untreated diabetes mellitus & individuals experiencing ↑ GH levels
What does GH indirectly mediate?
- Growth & protein synthesis by triggering liver & other tissues to produce insulin-like growth factors (IGFs)
What do insulin-like growth factors (IGFs) do?
- Enhances cellular proliferation & inhibits apoptosis
- Stimulates cells to ↑ uptake of amino acids from blood for protein synthesis
- Skeletal muscle & cartilage cells are particularly sensitive to stimulation from these proteins
What is gigantism and what causes it?
- Disorder in children thats caused by secretion of abnormally ↑ amounts of GH → results in excessive growth
What is acromegaly and what causes it?
- A similar condition to gigantism in adults → disorder that results in growth of bones in face, hands & feet in response to ↑↑ levels of GH in individuals who have stopped growing
What is pituitary dwarfism and what causes it?
(also known as growth hormone deficiency)
- Abnormally ↓↓ levels of GH in children can cause growth impairment → resulting in this condition
What regulates the activity of the thyroid gland?
- Thyroid-stimulating hormone (TSH) (or thyrotropin)
When is TSH released from the adenohypophysis?
- In response to thyrotropin-releasing hormone (TRH) from hypothalamus → triggers secretion of thyroid hormones by thyroid gland
What precursor molecule does adrenocorticotropic hormone (ACTH) come from?
- Pro-opiomelanotropin (POMC) → produces several biologically active molecules when cleaved → including ACTH, melanocyte-stimulating hormone & brain opioid peptides (endorphins)
What is the release of ACTH regulated by?
- Corticotropin-releasing hormone (CRH) from hypothalamus in response to normal physiologic rhythms
- Variety of stressors can also influence its release
What is puberty initiated by?
- Gonadotropin-releasing hormone (GnRH) → hormone produced & secreted by hypothalamus
What does gonadotropin-releasing hormone (GnRH) do?
- Stimulates adenohypophysis to secrete gonadotropins → hormones that regulate function of gonads
Are the levels of GnRH regulated through a positive or negative feedback loop?
- Negative → ↑ levels of reproductive hormones inhibit release of GnRH
- Throughout life gonadotropins regulate reproductive function
The gonadotropins consist of 2 glycoprotein hormones, what are they?
- Follicle-stimulating hormone (FSH)
- Luteinizing hormone (LH)
What does FSH do?
- Stimulates production & maturation of gametes
- FSH promotes follicular growth → these follicles then release estrogens in female ovaries.. fuckin lovely
What does LH do?
- Triggers ovulation in women, as well as production of estrogens & progesterone by ovaries.. fuck
- LH stimulates production of testosterone by male testes.. sigh*
What does prolactin (PRL) do?
- Promotes lactation in women.
During pregnancy, what does prolactin (PRL) do?
- Contributes to development of mammary glands
- After birth → stimulates mammary glands to produce breast milk
- Effects of prolactin depend heavily upon permissive effects of estrogens, progesterone & other hormones
And as noted earlier, the let-down of milk occurs in response to stimulation from oxytocin.. mkay?**
- Okie dokie **
In nonpregnant women, what is PRL secretion inhibited by?
- Prolactin-inhibiting hormone (PIH) (or dopamine) → released from neurons in hypothalamus.
In pregnant women, what do prolactin levels rise in response to?
- Prolactin-releasing hormone (PRH) from hypothalamus
What do cells in the intermediate pituitary gland secrete?
- Melanocyte-stimulating hormone (MSH)
How is melanocyte-stimulating hormone (MSH) formed?
- Cleavage of pro-opiomelanocortin (POMC) precursor protein.
- Local production of MSH in skin is responsible for melanin production in response to UV light exposure
Do people with lighter skin have the same amount of MSH as someone who has darker skin?
- Yes, this hormone is capable of darkening skin by inducing melanin production in skin’s melanocytes
In pregnant women, pigmentation of skin particularly the areolas & labia minora are common, why is this?
- ↑ MSH in combination with estrogen
Where is the thyroid gland located?
- Anterior to trachea, just inferior to larynx
What is the medial region of the thyroid gland called?
- Isthmus → flanked by wing-shaped L&R lobes.
- Each thyroid lobe is embedded with parathyroid glands → primarily on their posterior surfaces
What is the tissue of the thyroid gland composed of?
- Mostly of thyroid follicles → they consist of single layer of thyroid epithelial cells surrounding follicular lumen
What is the follicular lumen filled with?
- Colloid → predominantly composed of thyroglobulin → large glycoprotein that serves as scaffold for thyroid hormone synthesis
What does the colloid of the thyroid follicle do?
- Literally center of thyroid hormone production
- Production dependent on hormones’ essential & unique component → iodine or iodide in body
What is the HPT axis?
- Hypothalamic Pituitary Thyroid axis
What does the paraventricular nucleus in the hypothalamus do?
- Secretes thyrotropin releasing hormone (TRH)
How does TRH get into the adenohypophysis?
- Via the hypophyseal portal system
What effect does TRH have on the anterior pituitary gland?
- Stimulates thyrotropes → they secrete thyroid stimulating hormone (TSH)
What does (thyroid stimulating hormone) TSH do?
- Binds to receptor present on external face of thyroid follicle
Once TSH has binded to the external face of the thyroid follicle, what does it activate?
- G proteins (G's)
When a hormone is not bound to the receptor of the thyroid follicle, what state are the G's in?
- Inactive & bound to GDP
When a hormone binds to a receptor of the thyroid follicle, what happens to the G's?
- Becomes activated by binding GTP, in place of GDP.
After binding, what happens to GTP?
- It gets hydrolysed by G-protein into GDP & becomes inactive.
What does the now activated G protein in turn activate?
- Mb-bound enzyme adenylyl cyclase
What does adenylyl-cyclase catalyze?
- Conversion of ATP → cyclic AMP
What does cAMP activate?
- Protein kinase A
What are the impacts of phosphorylating a substrate molecule?
- Changes its structural orientation, thereby activating it
What do the protein kinase A's do?
- Transfer a phosphate group from ATP to a substrate molecule (phosphorylation)
Once protein kinase phosphorylates the transcription factor, what does the transcription factor do?
- Starts stimulating genes for specific protein
As we know, mRNA goes to RER where complementary proteins are produced via translation, then to Golgi where its packed/modified into vesicles. What happens after this?
- Those vesicles fuse to the bilayer → thyroglobulin colloid is released into luminal space via exocytosis
With a thyroglobulin colloid being produced, it comes time for the iodine dependent biochemical reactions.. so first, where does thyroid hormone synthesis occur?
- In follicles → functional units of thyroid gland
What are the 2 principle materials needed for making thyroid hormones?
- Iodine → which have on their outer plasma mb a sodium-iodide symporter or "iodine trap"
What are tyrosines and how are they provided?
- From large glycoprotein (thyroglobulin) → synthesized by thyroid epithelial cells/ follicular cells & secreted into lumen of follicle
- Colloid- essentially just pool of thyroglobulin
How many tyrosines does 1 thyroglobulin molecule have?
- 134 tyrosines, although only handful of these are actually used to synthesize T3 & T4
What is the blood form of iodine called, and what are its concentrations intracellularly vs extracellularly?
- Iodide (I-)
- ↑ intracellularly
- ↓ extracellularly
What are the concentrations of Na+ intracellularly vs extracellularly?
- ↓ Intracellularly
- ↑ Extracellularly
What does the synthesis of thyroid hormones require?
- Uptake of iodide across basolateral mb into thyrocytes (or follicular cells) → transport across cell → efflux through apical mb into follicular lumen
What provides the energy required to produce the Na+ gradient?
- Ouabain-sensitive Na+/K+-ATPase
What is uptake of iodide mediated by?
- Sodium-iodide symporter (NIS) → cotransports 2 Na+ ions along with 1 I- ion
- Na+ gradient serving as driving force
What another name for the sodium-iodide symporter (NIS)?
- Iodine trap
What plays at least a partial role in mediating the efflux of iodide across the apical mb?
Once iodide reaches the cell-colloid interface, what happens from there?
- Oxidized & rapidly organified by incorporation into selected tyrosyl residues of thyroglobulin (known as organification or iodination)
What enzyme catalyzes the iodination of tyrosines on thyroglobulin?
(also known as "organification of iodide")
- Thyroid peroxidase (TP) → I- to I2
- Catalyzes in presence of hydrogen peroxide → results in formation of mono- & diiodotyrosines (MIT & DIT)
MIT + DIT =
- T3 (triiodothyronine)
DIT + DIT =
- T4 (Thyroxine)
What enzyme catalyzes the synthesis of thyroxine or triiodothyronine from 2 iodotyrosines to form either T 3 or T 4?
- It'd be thyroid peroxidase (TP)
What is the generation of hydrogen peroxide mediated by?
- Calcium-dependent reduced nicotinamide adenine dinucleotide phosphate (NADPH)
- Dual oxidase type 2 (DUOX2)
To release thyroid hormones, what must happen first?
and then secreted into the bloodstream at the basolateral membrane (2).
- Thyroglobulin complex engulfed into via pinocytosis → lysosomal enzymes in cell isolate T3 & T4
Once the lysosomal enzymes have isolated the now functional T3 & T4 it must exit the follicular cell, how does this work?
- Vesicle fuses to the cell mb → then released out into the bloodstream to reach its target organs
Since T3 & T4 have a benzene ring and are not H2O soluble, what does the liver synthesize to assist in their transportation?
- Thyroxine binding globulin (TBG)
So summed up, what are the 4 stages of making thyroid hormones?
- Iodine trapping → iodination/ organification → coupling → release
Step 1 of making thyroid hormones:
- TRH released from paraventricular nucleus of hypothalamus
Step 2 of making thyroid hormones:
- TRH stimulates thyrotropes in adenohypophysis to release TSH
Step 3 of making thyroid hormones:
- TSH stimulates follicular cells to synthesize thyroglobulin
Step 4 of making thyroid hormones:
- Iodide trapping via sodium-iodide symporter
Step 5 of making thyroid hormones:
- Oxidation of I- ions via the actions of thyroid peroxidase
Step 6 of making thyroid hormones:
- Iodinate Tyrosine aa
Step 7 of making thyroid hormones:
- Couple DIT's & MIT's
Step 8 of making thyroid hormones:
- Endocytosis of thyroglobulin colloid with T3 & T4 in it
Step 9 of making thyroid hormones:
- Lysosomal enzymes cleave T3 & T4 out of globulin
Step 10 of making thyroid hormones:
- Exocytosis of T3 & T4 into blood plasma bound to thyroxine-binding globulins
Are the levels of TRH, TSH, T3 & T4 regulated by a positive or negative feedback system?
- Negative → ➚ levels of T3 & T4 → ↓ production & secretion of TSH
What are T3 & T4 often referred to as?
- Metabolic hormones → since their levels influence body’s BMR
What happens when T3 & T4 bind to intracellular receptors located on the mitochondria?
- ↑ nutrient breakdown
- ↑ use of O2 to produce ATP → calorigenic effect (calor- = “heat”) → ↑ body temperature
- Initiates transcription of genes involved in glucose oxidation (though process is inefficient)
When T3 & T4 cannot be produced, TSH is secreted in increasing amounts, what are the consequences of this?
- Hyperstimulation → thyroglobulin accumulates in thyroid gland follicles → ↑ deposits of colloid.
- Its the accumulation of colloid that ↑ overall size of thyroid gland (goiter)
What is neonatal hypothyroidism (cretinism)?
- Its characterized by cognitive deficits, short stature & sometimes deafness & muteness in children & adults born to mothers who were iodine- deficient during pregnancy.
What is hypothyroidism characterized by?
- ↓ metabolic rate, weight gain, cold extremities, constipation, reduced libido, menstrual irregularities & reduced mental activity
What is hyperthyroidism characterized by?
- ↑ metabolic rate, hyperthermia & sweating, diarrhea, weight loss, tremors & ↑ heart rate.
What is hyperthyroidism in a nutshell?
- Abnormally ↑ blood level of thyroid hormones - often caused by pituitary or thyroid tumor
In Graves’ disease, what does the hyperthyroid state result from?
- Autoimmune reaction in which antibodies overstimulate follicle cells of thyroid gland.
What produces the hormone calcitonin?
- Produced by parafollicular cells (also called C cells) of thyroid gland that stud tissue between distinct follicles.
- Released in response to a ↑ in blood calcium levels.
Calcitonin appears to have a function in decreasing blood calcium concentrations in 4 different ways, what are they?
- Inhibiting (↓) activity of osteoclasts → bone cells that release calcium into circulation by degrading bone matrix
- ↑ osteoblastic activity
- ↓ calcium absorption in intestines
- ↑ calcium loss in urine
- Functions usually not significant in maintaining calcium homeostasis, so importance of calcitonin is not entirely understood.