Week‌‌1‌‌–‌‌Endocrinology‌‌I‌ ‌
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Define‌‌endocrine,‌‌autocrine‌‌&‌‌paracrine,‌‌target‌‌cell,‌‌hormone‌ ‌
● Endocrine‌‌–‌‌hormones‌‌that‌‌are‌‌secreted‌‌into‌‌the‌‌bloodstream‌‌&‌‌transported‌‌to‌‌target‌‌cells‌‌where‌‌they‌‌produce‌‌their‌‌physiological‌‌
effect‌ ‌
● Autocrine‌‌–‌‌hormone‌‌that‌‌is‌‌secreted‌‌into‌‌extracellular‌‌fluid‌‌&‌‌acts‌‌upon‌‌the‌‌cell‌‌that‌‌produces‌‌it‌ ‌
● Paracrine‌‌–‌‌a‌‌hormone‌‌that‌‌exerts‌‌its‌‌effects‌‌on‌‌cells‌‌near‌‌its‌‌secretion‌‌site‌‌(excludes‌‌neurotransmitters),‌‌but‌‌not‌‌the‌‌cell‌‌that‌‌
produced‌‌it‌ ‌
○ Acts‌‌within‌‌the‌‌organ‌‌it‌‌is‌‌produced‌ ‌
● Target‌‌Cell‌‌–‌‌hormones‌‌that‌‌affect‌‌only‌‌these‌‌cells‌‌b/c‌‌they‌‌have‌‌specific‌‌receptors‌‌that‌‌will‌‌bind‌‌the‌‌hormone‌ ‌
● Hormones‌‌–‌‌Chemical‌‌messengers‌‌that‌‌are‌‌secreted‌‌from‌‌the‌‌endocrine‌‌gland‌‌or‌‌tissue‌ ‌
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Describe‌‌&‌‌give‌‌examples‌‌of‌‌negative‌‌&‌‌positive‌‌feedback‌‌loops‌ ‌
● Since‌‌endocrines‌‌have‌‌tendencies‌‌to‌‌over-secrete‌‌its‌‌hormone,‌‌it‌‌will‌‌have‌‌more‌‌of‌‌an‌‌effect‌‌on‌‌the‌‌target‌‌organ‌ ‌
● Negative‌‌feedback‌‌loops‌‌=‌‌target‌‌gland‌‌hormones‌‌act‌‌on‌‌endocrine‌‌glands‌‌to‌‌stimulate‌‌or‌‌inhibit‌‌their‌‌production‌‌(E.g.‌‌T4‌‌can‌‌inhibit‌‌
the‌‌TRH‌‌from‌‌the‌‌hypothalamus‌‌or‌‌TSH‌‌from‌‌the‌‌anterior‌‌pituitary)‌ ‌
● Positive‌‌feedback‌‌loops‌‌=‌‌↑ed‌‌levels‌‌of‌‌target‌‌gland‌‌hormones‌‌stimulates‌‌endocrine‌‌glands‌‌to‌‌secrete‌‌more‌‌(E.g.‌‌estradiol‌‌stimulates‌‌
anterior‌‌pituitary‌‌to‌‌secrete‌‌LH‌‌for‌‌ovulation)‌ ‌
● If‌‌too‌‌much‌‌function‌‌occurs,‌‌usually‌‌some‌‌factors‌‌are‌‌associated‌‌w/‌‌the‌‌function‌‌feedback‌‌on‌‌the‌‌“control”‌‌gland‌‌to‌‌reduce‌‌hormone‌‌
secretion‌ ‌
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Discuss‌‌the‌‌relationship‌‌b/w‌‌the‌‌nervous‌‌&‌‌endocrine‌‌systems‌ ‌
● The‌‌hypothalamus‌‌is‌‌a‌‌portion‌‌of‌‌the‌‌brain‌‌that‌‌maintains‌‌the‌‌bodies‌‌internal‌‌balance‌‌(homeostasis)‌ ‌
● The‌‌hypothalamus‌‌is‌‌the‌‌link‌‌b/w‌‌the‌‌endocrine‌‌&‌‌nervous‌‌systems.‌‌The‌‌hypothalamus‌‌produces,‌‌releasing‌‌&‌‌inhibiting‌‌hormones,‌‌
which‌‌stop‌‌the‌‌production‌‌of‌‌other‌‌hormones‌‌throughout‌‌the‌‌body.‌ ‌
○ Important‌‌for‌‌growth,‌‌reproduction,‌‌metabolism,‌‌etc.‌ ‌
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Describe‌‌Amine‌‌hormones‌‌&‌‌identify‌‌members‌‌of‌‌this‌‌classification‌ ‌
● Hormones‌‌that‌‌are‌‌derived‌‌from‌‌the‌‌amino‌‌acid‌‌tyrosine‌‌&‌‌include‌‌adrenaline‌ ‌
● They‌‌include‌‌two‌‌thyroid‌‌hormones‌‌(thyroxine‌‌[T4]‌‌&‌‌triiodothyronine‌‌[T3]),‌‌hormones‌‌of‌‌the‌‌adrenal‌‌medulla‌‌(adrenaline‌‌&‌‌
noradrenaline)‌‌as‌‌well‌‌as‌‌melatonin‌‌(produced‌‌by‌‌pineal‌‌gland)‌ ‌
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Identify‌‌common‌‌peptide‌‌&‌‌protein‌‌hormones‌ ‌
● These‌‌hormones‌‌are‌‌either‌‌small‌‌peptides‌‌or‌‌proteins‌‌which‌‌are‌‌synthesized‌‌on‌‌the‌‌ribosomes‌‌of‌‌endocrine‌‌cells‌ ‌
● Adrenocorticotropic‌‌hormone‌‌(ACTH)‌‌&‌‌melanocyte‌‌stimulating‌‌hormone‌‌(MSH)‌‌are‌‌common‌‌&‌‌come‌‌from‌‌a‌‌single‌‌prohormone‌ ‌
● Calcitonin,‌‌amylin‌‌&‌‌angiotensin‌‌are‌‌other‌‌common‌‌ones‌ ‌
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Describe‌‌the‌‌synthesis‌‌&‌‌release‌‌of‌‌peptide‌‌&‌‌protein‌‌hormones‌ ‌
1) Synthesized‌‌on‌‌the‌‌ribosomes‌‌of‌‌endocrine‌‌cells‌‌as‌‌larger‌‌proteins‌‌known‌‌as‌‌preprohormones‌‌&‌‌then‌‌cleaved‌‌to‌‌prohormones‌‌by‌‌
enzymes‌‌in‌‌the‌‌granular‌‌endoplasmic‌‌reticulum‌‌(ER)‌‌of‌‌the‌‌cell‌ ‌
2) The‌‌prohormone‌‌is‌‌then‌‌packaged‌‌into‌‌secretory‌‌vesicles‌‌by‌‌the‌‌Golgi‌‌apparatus‌ ‌
3) It‌‌is‌‌then‌‌cleaved‌‌to‌‌become‌‌the‌‌final‌‌hormone‌‌&‌‌leftover‌‌peptides‌ ‌
a) Both‌‌are‌‌released‌‌by‌‌exocytosis‌‌in‌‌response‌‌to‌‌specific‌‌stimuli‌ ‌
b) In‌‌some‌‌cases,‌‌the‌‌other‌‌peptides‌‌may‌‌have‌‌effects‌‌on‌‌target‌‌cells‌ ‌
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Identify‌‌common‌‌steroid‌‌hormones‌ ‌
● Cholesterol‌‌is‌‌the‌‌most‌‌common‌‌steroid‌‌hormone,‌‌&‌‌all‌‌the‌‌others‌‌have‌‌a‌‌similar‌‌chemical‌‌structure‌‌&‌‌actually‌‌derived‌‌from‌‌
cholesterol‌‌itself‌ ‌
● Other‌‌common‌‌ones‌‌include‌‌Aldosterone,‌‌Cortisol,‌‌Corticoids,‌‌etc‌ ‌
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Describe‌‌the‌‌synthesis‌‌&‌‌release‌‌of‌‌steroid‌‌hormones‌ ‌
● Some‌‌endocrines‌‌synthesize‌‌their‌‌own‌‌cholesterol,‌‌but‌‌it‌‌is‌‌mostly‌‌derived‌‌from‌p
‌ lasma‌‌lipoproteins‌‌‌that‌‌are‌‌made‌‌in‌‌the‌‌liver‌‌&‌‌
circulate‌‌the‌‌blood‌ ‌
● Steroid‌‌hormones‌‌are‌‌highly‌‌lipid‌‌soluble‌‌&‌‌once‌‌synthesized,‌‌can‌‌diffuse‌‌across‌‌the‌‌plasma‌‌membrane‌‌&‌‌enter‌‌the‌‌bloodstream‌ ‌
○ Therefore,‌‌large‌‌quantities‌‌of‌‌steroid‌‌hormones‌‌are‌‌not‌‌stored‌‌within‌‌the‌‌synthesizing‌‌cell‌‌but‌‌their‌‌precursors‌‌are‌ ‌
● Upon‌‌appropriate‌‌stimulation,‌‌enzymes‌‌in‌‌these‌‌cells‌‌can,‌‌within‌‌minutes,‌‌cause‌‌the‌‌chemical‌‌conversion‌‌to‌‌the‌‌final‌‌hormones‌‌
ready‌‌for‌‌secretion‌ ‌
‌ ‌
Discuss‌‌transport‌‌&‌‌delivery‌‌of‌‌hormones‌‌to‌‌target‌‌cells‌ ‌
Hormones‌‌Transport‌‌in‌‌Blood‌
● Water-soluble‌‌hormones‌‌‌(adrenaline,‌‌noradrenaline‌‌&‌‌peptides)‌‌are‌‌carried‌‌in‌‌the‌‌plasma‌‌in‌‌a‌‌dissolved‌‌state‌‌to‌‌their‌‌target‌‌organ(s)‌ ‌
● The‌‌steroid‌‌&‌‌thyroid‌‌hormones‌‌ARE‌‌NOT‌‌very‌‌water-soluble‌‌&‌‌circulate‌‌in‌‌the‌‌blood‌b
‌ ound‌‌to‌‌plasma‌‌proteins‌ ‌
○ Some‌‌of‌‌these‌‌proteins‌‌are‌‌specifically‌‌for‌‌the‌‌transport‌‌of‌‌the‌‌hormone;‌‌other‌‌plasma‌‌proteins‌‌(albumin)‌‌can‌‌carry‌‌almost‌‌
any‌l‌ipid-soluble‌‌hormone‌ ‌
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Hormone‌‌Delivery‌‌to‌‌Target‌‌Cell‌ ‌
● Most‌‌of‌‌a‌‌lipid-soluble‌‌hormone‌‌is‌‌bound‌‌to‌‌its‌‌plasma‌‌protein‌‌but‌‌a‌‌small‌‌amount‌‌exists‌‌as‌‌free,‌‌unbound‌‌hormone‌‌dissolved‌‌in‌‌
plasma‌ ‌
○ It‌‌is‌‌only‌‌the‌‌free‌‌hormone‌‌that‌‌can‌‌cross‌‌capillary‌‌walls‌‌&‌‌affect‌‌its‌‌target‌‌organ‌ ‌
○ There‌‌exist‌‌specific‌‌protein‌‌transporters‌‌which‌‌facilitate‌‌the‌‌passage‌‌of‌‌these‌‌hormones‌‌through‌‌capillary‌‌endothelium‌ ‌
○ Ex.‌‌specific‌‌binding‌‌sites‌‌for‌‌T3‌‌&‌‌T4‌‌have‌‌been‌‌identified‌‌in‌‌plasma‌‌membrane,‌‌cell‌‌nuclei‌‌&‌‌mitochondria‌‌of‌‌various‌‌organs‌‌
&‌‌it‌‌is‌‌possible‌‌that‌‌the‌‌entry‌‌of‌‌thyroid‌‌hormones‌‌is‌‌driven‌‌by‌‌the‌e
‌ quilibrium‌‌‌b/w‌‌the‌‌extracellular‌‌&‌‌intracellular‌‌thyroid‌‌
hormone‌‌binding‌‌protein‌ ‌
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Identify‌‌mechanisms‌‌of‌‌the‌‌body‌‌that‌‌metabolize‌‌&‌‌clear‌‌hormones‌‌from‌‌circulation‌ ‌
● For‌‌protein‌‌hormones‌‌–‌‌they‌‌are‌‌secreted‌‌to‌‌peripheral‌‌circulation‌‌as‌‌a‌‌mix‌‌of‌‌isoforms.‌‌These‌‌heterodimeric‌‌hormones‌‌consist‌‌of‌‌
amino‌‌acid‌‌chains‌‌&‌‌N-linked‌‌glycosylation‌‌sites‌‌where‌‌multiple‌‌oligosaccharide‌‌residues‌‌can‌‌be‌‌added‌ ‌
○ Glycosylation‌‌adds‌‌a‌‌high‌‌proportion‌‌of‌‌sialic‌‌acid-enriched‌‌carbohydrates‌‌&‌‌a‌‌lesser‌‌number‌‌of‌‌sulphated‌‌residues‌‌to‌‌
protein‌‌molecules‌ ‌
● Deglycosylation‌‌‌&‌p
‌ roteolysis‌‌‌are‌‌the‌‌major‌‌mechanisms‌‌of‌‌inactivation‌‌&‌‌clearance‌‌of‌‌specific‌‌glycoprotein‌‌hormones‌ ‌
● Terminal‌s‌ ialic‌‌acid‌‌residues‌‌are‌‌typically‌‌removed‌‌by‌‌plasma‌‌glycosidases‌ ‌
● Hepatic‌‌cells‌‌then‌‌recognize‌‌the‌‌“expose”‌‌hormone‌‌&‌‌peptide‌‌bonds‌‌b/w‌‌amino‌‌acids‌‌become‌‌susceptible‌‌to‌‌enzymatic‌‌attack‌ ‌
○ Note:‌‌the‌‌less‌‌glycosylated/acidic‌‌isoforms‌‌of‌‌protein‌‌hormones‌‌exhibit‌‌a‌‌shorter‌‌half-life‌‌in‌‌systemic‌‌circulation‌‌than‌‌their‌‌
more‌‌acidic‌‌counterparts‌ ‌
○ Most‌‌acidic‌‌isoforms‌‌(degree‌‌of‌‌sialylation‌‌&‌‌sulphation)‌‌are‌‌more‌‌potent‌‌stimulators‌‌of‌‌target‌‌organs.‌ ‌
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Describe‌‌phasic‌‌(surge-like),‌‌episodic‌‌(pulsatile),‌‌circadian‌‌&‌‌cyclic‌‌modes‌‌of‌‌hormone‌‌secretion‌ ‌
● Phasic‌‌(surge-like):‌‌‌sudden‌‌change‌‌(a‌‌bolt‌‌of‌‌a‌‌large‌‌amount‌‌of‌‌hormone)‌ ‌
● Episodic‌‌(pulsatile):‌‌‌to‌‌prevent‌‌desensitization‌‌from‌‌occurring‌‌under‌‌normal‌‌conditions.‌‌They‌‌are‌‌secreted‌‌in‌‌spurts‌‌rather‌‌than‌‌
continuously‌ ‌
● Circadian:‌‌‌rhythms‌‌that‌‌follow‌‌a‌‌24‌‌four‌‌pattern‌ ‌
● Cyclic:‌i‌t‌‌occurs‌‌in‌‌a‌‌cycle,‌‌whether‌‌a‌‌month‌‌or‌‌day‌ ‌
● Circannual‌‌modes:‌‌‌yearly/seasonally‌ ‌
○ Note:‌‌the‌‌greatest‌‌release‌‌of‌‌growth‌‌hormone‌‌occurs‌‌during‌‌the‌‌early‌‌sleep‌‌period‌ ‌
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Define‌‌synergistic,‌‌permissive‌‌&‌‌antagonist‌‌effects‌‌of‌‌hormone‌‌actions‌ ‌
● Synergistic‌‌–‌‌When‌‌two‌‌hormones‌‌work‌‌together,‌‌their‌‌effects‌‌can‌‌be‌‌additive‌‌or‌‌complementary.‌‌Two‌‌or‌‌more‌‌hormones‌‌work‌‌
together‌‌to‌‌produce‌‌a‌‌particular‌‌result‌ ‌
○ Ex.‌‌epinephrine‌‌&‌‌norepinephrine‌‌–‌‌produce‌‌in‌‌additive‌‌affect‌‌in‌‌the‌‌heart‌‌as‌‌they‌‌each‌‌separately‌‌produces‌‌an‌↑
‌ ‌‌in‌‌cardia‌‌
rate‌‌which‌‌becomes‌‌even‌‌greater‌‌at‌‌the‌‌same‌‌concentrations‌‌when‌‌together‌ ‌
● Permissive‌‌–‌h
‌ as‌‌an‌‌accommodating‌‌effect‌‌on‌‌the‌‌action‌‌of‌‌a‌‌second‌‌hormone‌‌when‌‌it‌‌enhances‌‌the‌‌responsiveness‌‌of‌‌a‌‌target‌‌
organ‌‌to‌‌the‌‌second‌‌hormone,‌‌or‌‌when‌‌it‌↑
‌ es‌‌the‌‌activity‌‌of‌‌the‌‌second‌‌hormone‌ ‌
○ Ex.‌‌PTH‌‌to‌‌Vitamin‌‌D3‌ ‌
●
Antagonistic‌‌–‌w
‌ orks‌‌against‌‌each‌‌other‌ ‌
○ Ex.‌‌insulin‌‌&‌‌glucagon‌‌on‌‌adipose‌‌tissue‌ ‌
■ Insulin‌‌promotes‌‌the‌‌formation‌‌of‌‌fat‌‌while‌‌glucagon‌‌promotes‌‌fat‌‌breakdown‌ ‌
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Describe‌‌the‌‌effects‌‌of‌‌hormone‌‌concentration‌‌on‌‌target‌‌tissues‌ ‌
● Effects‌‌of‌‌hormones‌‌are‌‌very‌‌dependent‌‌on‌‌concentration‌‌–‌‌when‌‌concentrations‌‌are‌‌high,‌‌their‌‌effects‌‌may‌‌be‌‌different‌ ‌
○ Pharmacological‌‌doses‌‌of‌‌hormones,‌‌especially‌‌steroids‌‌can‌‌have‌‌very‌‌damaging‌‌side‌‌effects‌
○ Priming‌‌Effects:‌‌‌variations‌‌in‌‌hormones‌‌within‌‌normal‌‌range‌‌can‌‌affect‌‌responsiveness‌‌of‌‌target‌‌cells‌‌due‌‌to‌‌the‌‌effect‌‌of‌‌
polypeptide‌‌&‌‌glycoprotein‌‌hormones‌‌on‌‌the‌‌number‌‌of‌‌their‌‌receptor‌‌proteins‌‌in‌‌target‌‌cell.‌ ‌More‌‌receptors‌‌may‌‌be‌‌
formed‌‌in‌‌target‌‌cell‌‌in‌‌response‌‌to‌‌this‌‌(up-regulation‌‌of‌‌receptors)‌ ‌
○ Desensitization‌‌&‌‌Downregulation:‌‌‌prolonged‌‌exposure‌‌to‌‌high‌‌concentration‌‌of‌‌polypeptide‌‌hormones‌‌has‌‌been‌‌found‌‌to‌‌
desensitize‌‌the‌‌target‌‌cells.‌‌This‌‌is‌‌due‌‌to‌‌the‌‌downregulation‌‌of‌‌receptors‌‌&‌‌it‌‌causes‌‌by‌‌continuous‌‌exposure‌‌of‌‌the‌‌target‌‌
cells‌‌to‌‌the‌‌hormone‌ ‌
● To‌‌prevent‌‌this,‌‌hormones‌‌are‌‌secreted‌‌in‌‌spurts‌‌(pulsatile‌‌secretion).‌‌ ‌
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Hormones‌‌in‌‌the‌‌Same‌‌Chemical‌‌Category:‌ ‌
● Binding‌‌is‌‌highly‌‌specific‌ ‌
● Hormones‌‌bind‌‌to‌‌receptors‌‌w/‌‌a‌‌high‌‌affinity‌ ‌
● Hormones‌‌bind‌‌to‌‌receptors‌‌w/‌‌a‌‌low‌‌capacity;‌‌saturating‌‌the‌‌receptors‌‌w/‌‌hormone‌‌molecules‌ ‌
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Discuss‌‌the‌‌Mechanisms‌‌of‌‌Action‌‌for‌‌of‌‌Amine‌‌&‌‌Peptide/Protein‌‌Hormones‌ ‌
Non-Steroid‌‌Action‌(‌ amine‌‌or‌‌peptide)‌‌‌hormones‌‌are‌p
‌ olar‌‌‌hormones‌‌&‌‌bind‌‌to‌‌receptors‌‌on‌‌plasma‌‌membrane‌‌where‌‌they‌‌exert‌‌their‌‌
effects‌‌through‌s‌ econd‌‌messenger‌‌systems‌ ‌
● Catecholamines,‌‌polypeptides‌‌&‌‌glycoproteins‌‌cannot‌‌pass‌‌through‌‌the‌‌plasma‌‌membrane‌ ‌
● Hormones‌‌are‌‌like‌‌messengers‌‌where‌‌the‌‌intracellular‌‌mediators‌‌of‌‌the‌‌hormones‌‌action‌‌can‌‌be‌‌second‌‌messengers‌ ‌
○ Second‌‌messengers‌‌are‌‌a‌‌part‌‌of‌‌signal-transduction‌‌mechanisms‌ ‌
○ Extracellular‌‌signals‌‌(hormones)‌‌are‌‌transduced‌‌into‌‌intracellular‌‌signals‌‌(second‌‌messengers)‌ ‌
■ Examples:‌‌adenylate‌‌cyclase,‌‌phospholipase‌‌C‌‌&‌‌tyrosine‌‌kinase‌‌are‌‌second‌‌messengers.‌ ‌
Adenylate‌‌Cyclase‌‌–‌‌Cyclic‌‌AMP‌‌(cAMP)‌ ‌
● Effects‌‌of‌‌many‌‌polypeptide‌‌glycoprotein‌‌hormones‌‌are‌‌mediated‌‌by‌‌cAMP‌ ‌
● When‌‌hormone‌‌binds‌‌to‌‌receptor‌‌protein,‌‌it‌‌causes‌‌dissociation‌‌of‌‌subunit‌‌from‌‌the‌‌complex‌‌of‌‌G-proteins,‌‌the‌‌subunit‌‌moves‌‌
through‌‌membrane‌‌until‌‌it‌‌reaches‌‌enzyme‌‌adenylate‌‌cyclase‌ ‌
● The‌‌G-proteins‌‌subunit‌‌binds‌‌&‌‌activates‌‌the‌‌enzymes,‌‌which‌‌catalyzes‌‌the‌‌reaction‌‌w/‌‌cytoplasm‌‌of‌‌the‌‌cell.‌ ‌
○ ATP‌‌cAMP‌‌+‌‌PPi‌
● This‌‌reaction‌‌causes‌‌an‌↑
‌ ‌‌in‌‌intracellular‌‌[cAMP]‌ ‌
● cAMP‌‌activates‌‌inactive‌‌enzyme‌‌in‌‌cytoplasm,‌‌protein‌‌kinase,‌‌by‌‌attaching‌‌to‌‌its‌‌regulatory‌‌subunit,‌‌causing‌‌it‌‌to‌‌dissociate‌‌from‌‌its‌‌
catalytic‌‌subunit,‌‌which‌‌too‌‌becomes‌‌active‌ ‌
○ ↑‌‌in‌‌cAMP‌‌production‌‌causes‌↑
‌ ‌‌of‌‌protein‌‌kinase‌‌enzyme‌‌activity‌ ‌
● Inactivation‌‌of‌‌cAMP‌‌must‌‌be‌‌rapidly‌‌done‌‌for‌‌it‌‌to‌‌function‌‌effectively‌‌&‌‌is‌‌accomplished‌‌by‌‌phosphodiesterase‌ ‌
● Cyclic‌‌guanosine‌‌monophosphate‌‌(cGMP)‌‌functions‌‌as‌‌a‌‌second‌‌messenger‌‌as‌‌well‌ ‌
‌
Phospholipase‌‌C‌‌–‌‌Ca‌2+‌ ‌
● Concentration‌‌of‌‌Ca2+‌‌in‌‌cytoplasm‌‌is‌‌kept‌‌very‌‌low‌‌by‌‌active‌‌transporter‌‌carriers‌‌(calcium‌‌pumps)‌‌in‌‌plasma‌‌membrane‌ ‌
● [Ca2+]‌‌is‌‌reduced‌‌to‌‌one‌‌ten-thousandth‌‌of‌‌its‌‌concentration‌‌in‌‌the‌‌extracellular‌‌fluid‌ ‌
● Endoplasmic‌‌reticulum‌‌contains‌‌Ca‌‌pumps‌‌to‌‌transport‌‌Ca2+‌‌from‌‌cytoplasm‌‌to‌‌cisternae‌ ‌
○ When‌‌muscles‌‌are‌‌contracted‌‌Ca2+‌‌couples‌‌w/‌‌electrical‌‌excitation‌‌of‌‌the‌‌muscle‌‌cell‌‌to‌‌mechanically‌‌contract‌‌muscle‌ ‌
● Stimulation‌‌of‌‌alpha-1-adrenergic‌‌receptors‌‌by‌‌epinephrine‌‌activates‌‌the‌‌target‌‌cell‌‌via‌‌Ca2+‌‌second‌‌messenger‌ ‌
○ This‌‌activates‌‌the‌‌enzyme‌‌in‌‌plasma‌‌membrane‌‌phospholipase‌‌C,‌‌the‌‌substrate‌‌of‌‌the‌‌enzyme‌‌is‌‌split‌‌into‌‌IP3‌‌(inositol‌
triphosphate)‌‌&‌‌DAG‌‌(diacylglycerol)‌‌–‌‌both‌‌of‌‌which‌‌act‌‌as‌‌second‌‌messengers‌ ‌
■ IP3‌‌leaves‌‌the‌‌plasma‌‌membrane‌‌&‌‌diffuses‌‌through‌‌cytoplasm‌‌to‌‌endoplasmic‌‌reticulum‌‌where‌‌receptor‌‌proteins‌
for‌‌IP3‌‌locate‌ ‌
■ The‌‌binding‌‌causes‌‌specific‌‌Ca2+‌‌channels‌‌to‌‌open,‌‌to‌‌diffuse‌‌Ca2+‌‌into‌‌cytoplasm,‌‌which‌‌binds‌‌a‌‌protein‌‌called‌‌
calmodulin,‌‌activating‌‌it‌‌&‌‌in‌‌turn,‌‌activates‌‌protein‌‌kinase‌‌enzymes‌ ‌
‌‌
Note:‌‌protein‌‌kinase‌‌enzymes‌ ‌are‌‌enzymes‌‌that‌‌regulate‌‌the‌‌biological‌‌activity‌‌of‌‌proteins‌‌by‌‌phosphorylation‌‌of‌‌specific‌‌amino‌‌acids‌‌w/‌‌ATP.‌ ‌
‌‌
Tyrosine‌‌Kinase‌‌Second‌‌Messenger‌‌Systems:‌ ‌
● Insulin‌‌promoters’‌‌glucose‌‌&‌‌amino‌‌acid‌‌transport‌‌&‌‌stimulates‌‌glycogen,‌‌fat,‌‌&‌‌protein‌‌synthesis‌‌in‌‌its‌‌target‌‌organs‌‌(liver,‌‌skeletal‌‌
muscles‌‌&‌‌adipose‌‌tissue)‌ ‌
● The‌‌growth‌‌factors‌‌including‌‌EGF‌‌(epidermal‌‌growth‌‌factor)‌‌&‌‌PDGF‌‌(platelet-derived‌‌growth‌‌factor)‌‌,‌‌IGF‌‌(insulin-like‌‌growth‌‌factor)‌ ‌
are‌‌autocrine‌‌regulators‌ ‌
○ In‌‌the‌‌case‌‌of‌‌insulin‌‌&‌‌growth‌‌factors,‌‌the‌‌receptor‌‌protein‌‌is‌‌located‌‌in‌‌the‌‌plasma‌‌membrane‌‌&‌‌is‌‌an‌‌enzyme‌‌called‌‌
Tyrosine‌‌Kinase‌‌(a‌‌kinase‌‌enzyme‌‌which‌‌adds‌‌a‌‌phosphate‌‌specifically‌‌to‌‌tyrosine‌‌amino‌‌acids)‌ ‌
● Insulin‌‌receptor‌‌consists‌‌of‌‌two‌‌alpha‌‌&‌‌two‌‌beta‌‌subunits‌ ‌
○ Alpha‌‌units‌‌in‌‌the‌‌extracellular‌‌side‌‌of‌‌plasma‌‌membrane‌‌&‌‌contain‌‌the‌‌ligand‌‌binding‌‌site‌‌&‌‌the‌‌beta‌‌units‌‌in‌‌the‌‌plasma‌‌
membrane‌ ‌
‌‌
When‌‌insulin‌‌binds‌‌to‌‌alpha‌‌units,‌‌the‌‌beta‌‌units‌‌are‌‌stimulated‌‌to‌‌phosphorylate‌‌each‌‌in‌‌a‌‌process‌‌called‌‌autophosphorylation‌‌which‌‌
activates‌‌the‌‌tyrosine‌‌kinase‌‌activity.‌ ‌
● Activated‌‌insulin‌‌receptor‌‌phosphorylates‌‌substrate‌‌proteins‌‌which‌‌activate‌‌a‌‌variety‌‌of‌‌signaling‌‌molecules‌ ‌
● These‌‌cause‌‌insertion‌‌of‌‌transport‌‌carrier‌‌proteins‌‌from‌‌glucose‌‌into‌‌plasma‌‌membrane‌‌which‌‌promote‌‌the‌‌uptake‌‌of‌‌plasma‌‌glucose‌‌
into‌‌tissue‌‌cells‌‌[lowers‌‌plasma‌‌glucose].‌ ‌
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Discuss‌‌the‌‌Mechanisms‌‌of‌‌Action‌‌for‌‌of‌‌Steroid/Thyroid‌‌Hormones‌ ‌
Unlike‌‌water-soluble‌‌hormones,‌‌the‌‌lipophilic‌‌&‌‌thyroid‌‌hormones‌‌do‌‌not‌‌travel‌‌dissolved‌‌in‌‌the‌‌aqueous‌‌portion‌‌of‌‌plasma;‌‌they‌‌use‌‌carrier‌‌
proteins.‌‌They‌‌dissociate‌‌from‌‌these‌‌carrier‌‌proteins‌‌once‌‌close‌‌to‌‌target‌‌cell‌‌&‌‌diffuse‌‌through‌‌the‌‌plasma‌‌membrane.‌ ‌
Receptors‌‌of‌‌lipophilic‌‌hormones‌‌are‌‌called‌n
‌ uclear‌‌hormone‌‌receptors‌‌(NHR)‌‌‌&‌‌function‌‌as‌‌transcription‌‌factors‌‌by‌‌activating‌‌genetic‌‌
transcription.‌‌They‌‌must‌‌first‌‌be‌‌activated‌‌by‌‌binding‌‌to‌‌their‌‌hormone‌‌ligands‌‌so‌‌that‌‌it‌‌can‌‌bind‌‌to‌‌a‌‌specific‌‌region‌‌of‌‌DNA‌‌called‌‌the‌‌
hormone-response‌‌element‌‌(HRE)‌.‌‌NRE‌‌has‌‌two‌‌regions/domains:‌‌(1)‌‌a‌‌ligand(hormone)-bind‌‌domain‌‌&‌‌(2)‌‌a‌‌DNA-binding‌‌domain.‌ ‌
‌
Steroid‌‌Hormone‌‌Mode‌‌of‌‌Action:‌ ‌
● Non-genomic‌‌action‌‌‌of‌‌steroids‌‌may‌‌occur‌‌in‌‌cytoplasm‌‌of‌‌target‌‌cells‌‌&‌‌involve‌‌the‌‌activation‌‌of‌‌second-messenger‌‌systems‌ ‌
● Stimulate‌‌genetic‌‌transcription‌(‌ genomic‌‌action)‌‌‌&‌‌takes‌‌some‌‌time‌‌to‌‌work‌ ‌
○ The‌‌receptors‌‌are‌‌in‌‌the‌‌cytoplasm,‌‌or‌‌sometimes‌‌unbound‌‌receptors‌‌can‌‌be‌‌found‌‌in‌‌nucleus‌ ‌
○ When‌‌cytoplasmic‌‌receptors‌‌(NREs)‌‌bind‌‌to‌‌their‌‌specific‌‌hormone‌‌ligands,‌‌they‌‌move‌‌to‌‌the‌‌nucleus‌‌where‌‌their‌‌
DNA-binding‌‌domains‌‌bind‌‌to‌‌the‌‌specific‌‌hormone-response‌‌element‌‌of‌‌the‌‌DNA‌ ‌
○ The‌‌hormone-response‌‌element‌‌of‌‌DNA‌‌consists‌‌of‌‌two‌‌half-sites‌‌(dimer)‌‌&‌‌since‌‌they‌‌are‌‌the‌‌same‌‌it‌‌is‌‌a‌‌homodimer‌ ‌
○ 1‌‌steroid-receptor‌‌bound‌‌to‌‌one‌‌hormone‌‌attaches‌‌a‌‌single‌‌unit‌‌to‌‌one‌‌half-site‌‌then‌‌the‌‌same‌‌for‌‌the‌‌other.‌ ‌
■ The‌‌activated‌‌receptors‌‌stimulate‌‌transcription‌‌of‌‌genes‌‌(hormonal‌‌regulation)‌ ‌
‌
When‌‌steroid‌‌hormone‌‌ligand‌‌binds‌‌to‌‌its‌‌nuclear‌‌receptor‌‌protein‌‌(NRP),‌‌it‌‌changes‌‌the‌‌receptor‌‌structure‌‌which‌‌causes:‌ ‌
a) Removal‌‌of‌‌a‌‌group‌‌of‌‌proteins‌‌(heat‌‌shock‌‌proteins)‌ ‌
b) Recruitment‌‌of‌‌coactivator‌‌proteins‌‌&‌‌prevention‌‌of‌‌corepressor‌‌proteins.‌ ‌
‌‌
Thyroid‌‌Hormone‌‌Mechanism‌‌of‌‌Action:‌ ‌
Major‌‌hormones‌‌secreted‌‌by‌‌thyroid‌‌gland‌‌is‌‌Thyroxine‌‌&‌‌it‌‌travels‌‌through‌‌blood‌‌w/‌‌a‌‌carrier‌‌protein‌‌TBH‌‌(thyroxine-binding‌‌globulin)‌ ‌
● Carrier‌‌proteins‌‌have‌‌higher‌‌affinity‌‌for‌‌T4‌‌than‌‌T3,‌‌therefore‌‌the‌‌amount‌‌of‌‌unbound‌‌T3‌‌is‌‌10X‌‌greater‌‌than‌‌T4‌ ‌
● Only‌‌free‌‌T3‌‌&‌‌T4‌‌can‌‌enter‌‌the‌‌target‌‌cells‌‌(bound‌‌ones‌‌serve‌‌as‌‌reservoir)‌ ‌
● Once‌‌free,‌‌T4‌‌passes‌‌into‌‌target‌‌cell,‌‌it‌‌is‌‌converted‌‌to‌‌T3‌ ‌
● Thyroid-hormone‌‌receptors‌‌(THR)‌‌are‌‌located‌‌in‌‌the‌‌nucleus‌‌&‌‌bound‌‌to‌‌DNA.‌ ‌
The‌‌thyroid‌‌hormone‌‌response‌‌element:‌ ‌
● Has‌‌two‌‌half‌‌sites‌‌but‌‌the‌‌thyroid‌‌hormone‌‌receptor‌‌(TR)‌‌for‌‌T3‌‌only‌‌binds‌‌to‌‌one‌‌of‌‌the‌‌half‌‌sites‌ ‌
● The‌‌other‌‌half‌‌site‌‌binds‌‌to‌‌the‌‌receptor‌‌for‌‌Vitamin‌‌A‌‌(RXR)‌ ‌
○ Creates‌‌heterodimer‌ ‌
‌‌
Identify‌‌the‌‌target‌‌of‌‌the‌‌following‌‌hypothalamic‌‌releasing/inhibiting‌‌factors:‌‌TRH,‌‌CRH,‌‌GHRH,‌‌somatostatin‌ ‌
TRH:‌‌‌stimulates‌‌secretion‌‌of‌‌TSH‌‌(Thyroid-stimulating‌‌hormone‌‌which‌‌is‌‌responsible‌‌for‌‌producing‌‌&‌‌secreting‌‌T4‌‌&‌‌T3.‌ ‌
CRH:‌‌‌stimulates‌‌secretion‌‌of‌‌ACTH‌‌(Adrenocorticotropic‌‌hormone)‌‌which‌‌stimulates‌‌adrenal‌‌cortex‌‌to‌‌secrete‌‌gluco-corticoids‌‌such‌‌as‌‌cortisol.‌ ‌
GHRH:‌‌‌secreted‌‌by‌‌hypothalamus‌‌that‌‌stimulates‌‌the‌‌anterior‌‌pituitary‌‌to‌‌secrete‌‌growth‌‌hormone,‌‌while‌‌somatostatin‌‌from‌‌hypothalamus‌‌
inhibits‌‌secretion.‌ ‌
‌‌
Identify‌‌the‌‌hormones‌‌of‌‌the‌‌anterior‌‌pituitary‌ ‌
1) Growth‌‌Hormone‌‌(GH,‌‌or‌‌somatotropin)‌ ‌
a) Promotes‌‌movement‌‌of‌‌amino‌‌acids‌‌into‌‌cells‌‌&‌‌incorporation‌‌of‌‌amino‌‌acids‌‌into‌‌proteins‌‌(promotes‌‌overall‌‌tissue‌‌&‌‌organ‌‌
growth)‌ ‌
2) Thyroid-stimulating‌‌Hormone‌‌(TSH‌‌or‌‌Thyrotropin)‌ ‌
a) Stimulates‌‌thyroid‌‌gland‌‌to‌‌produce‌‌&‌‌secrete‌‌T4‌‌&‌‌T3‌ ‌
3) Adrenocorticotropic‌‌Hormone‌‌(ACTH,‌‌or‌‌corticotropin)‌ ‌
a) Stimulates‌‌adrenal‌‌cortex‌‌to‌‌secrete‌‌gluco-corticoids,‌‌such‌‌as‌‌cortisol‌ ‌
4) Follicle-stimulating‌‌Hormone‌‌(FSH,‌‌folliculotropin)‌ ‌
a) Stimulates‌‌growth‌‌of‌‌ovarian‌‌follicles‌‌in‌‌females‌‌&‌‌the‌‌production‌‌of‌‌sperm‌‌cells‌‌in‌‌testes‌‌of‌‌males‌ ‌
5) Luteinizing‌‌Hormone‌‌(LH,‌‌or‌‌luteotropin)‌ ‌
a) w/‌‌FSH,‌‌collectively‌‌called‌‌gonadotropic‌‌hormones‌ ‌
b) Stimulates‌‌ovulation‌‌&‌‌stimulates‌‌secretion‌‌of‌‌male‌‌sex‌‌hormones‌‌(testosterone).‌ ‌
6) Prolactin‌‌(PRL)‌ ‌
a) Stimulation‌‌of‌‌milk‌‌production‌ ‌
b) Lactation‌ ‌
c) Supports‌‌water‌‌regulation‌‌&‌‌electrolyte‌‌balance‌ ‌
‌
Describe‌‌the‌‌general‌‌effects‌‌of‌‌growth‌‌hormone‌ ‌
● Growth‌‌hormone‌‌causes‌‌growth‌‌of‌‌almost‌‌all‌‌tissues‌‌of‌‌the‌‌body‌‌that‌‌are‌‌capable‌‌of‌‌growing‌ ‌
● Causes‌‌cells‌‌to‌↑
‌ ‌‌in‌‌size,‌‌↑ed‌‌mitosis‌‌&‌‌specific‌‌differentiation‌‌of‌‌certain‌‌types‌‌of‌‌cells‌‌such‌‌as‌‌bone‌‌growth‌‌cells‌‌&‌‌early‌‌muscle‌‌cells‌ ‌
● Deficiencies‌‌in‌‌growth‌‌hormone‌‌secretion‌‌may‌‌be‌‌congenital‌‌or‌‌they‌‌may‌‌occur‌‌slowly,‌‌or‌‌suddenly,‌‌at‌‌any‌‌time‌‌in‌‌life‌ ‌
‌
Describe‌‌the‌‌regulation‌‌of‌‌growth‌‌hormone‌‌secretion‌ ‌
● Growth‌‌hormone‌‌secretion‌‌is‌‌regulated‌‌by‌‌growth‌‌hormone‌‌releasing‌‌hormone‌‌(GHRH)‌‌&‌‌growth‌‌hormone‌‌inhibiting‌‌hormone‌‌
(GHIG,‌‌SRIF)‌ ‌
○ These‌‌are‌‌secreted‌‌by‌‌the‌‌hypothalamus‌‌&‌‌transported‌‌to‌‌the‌‌anterior‌‌pituitary‌‌gland‌‌through‌‌the‌‌
hypothalamic-hypophyseal‌‌portal‌‌vessels‌ ‌
○ Some‌‌of‌‌the‌‌same‌‌signals‌‌that‌‌initiate‌‌feedings‌‌also‌‌stimulate‌‌the‌‌secretion‌‌of‌‌growth‌‌hormone‌ ‌
‌
Describe‌‌the‌‌effects‌‌of‌‌growth‌‌hormone‌‌on‌‌the‌‌metabolism‌‌of‌‌proteins,‌‌fatty‌‌acids‌‌&‌‌glucose‌ ‌
Growth‌‌Hormone‌‌Protein‌‌Metabolism:‌ ‌
● ↑es‌‌the‌‌rate‌‌of‌‌protein‌‌synthesis‌‌through‌‌a‌‌mechanism‌‌not‌‌fully‌‌understood‌ ‌
● It‌‌also‌‌enhances‌‌the‌‌transport‌‌of‌‌amino‌‌acids‌‌into‌‌the‌‌cell‌ ‌
● Even‌‌in‌‌the‌‌absence‌‌of‌‌high‌‌concentration‌‌of‌‌amino‌‌acids,‌‌growth‌‌hormones‌↑
‌ ‌‌RNA‌‌translation‌‌which‌‌stimulate‌‌protein‌‌synthesis‌ ‌
‌
Growth‌‌Hormone‌‌Fatty‌‌Acid‌‌Metabolism:‌ ‌
● Growth‌‌hormone‌‌not‌‌only‌↑
‌ es‌‌the‌‌mobilization‌‌of‌‌fatty‌‌acids‌‌from‌‌adipose‌‌tissue,‌‌it‌‌enhances‌‌the‌‌conversion‌‌of‌‌fatty‌‌acids‌‌to‌‌
acetyl-CoA‌ ‌
○ Fat‌‌is‌‌utilized‌‌for‌‌energy‌‌preferentially‌‌over‌‌carbohydrates‌‌&‌‌proteins‌ ‌
● If‌‌an‌‌excessive‌‌quantity‌‌of‌‌growth‌‌hormone‌‌&‌‌large‌‌amounts‌‌of‌‌fat‌‌are‌‌being‌‌mobilized,‌‌excess‌‌amounts‌‌of‌‌acetoacetic‌‌acid‌‌are‌‌
formed‌‌in‌‌the‌‌liver‌‌&‌‌a‌‌condition‌‌called‌‌ketosis‌‌develops.‌ ‌
‌
Growth‌‌Hormone‌‌Glucose‌‌Metabolism:‌ ‌
● Growth‌‌Hormones‌‌cause‌‌an‌↑
‌ ‌‌in‌‌blood‌‌glucose‌‌levels‌‌which‌‌triggers‌‌the‌‌release‌‌of‌‌insulin‌‌from‌‌the‌‌pancreas‌ ‌
● Decreases‌‌the‌‌utilization‌‌of‌‌glucose‌‌by‌‌suppressing‌‌glucose‌‌uptake‌‌&‌‌glucose‌‌oxidation‌‌&‌‌stimulates‌‌glycogenesis‌ ‌
‌
Discuss‌‌how‌‌growth‌‌hormone‌‌impacts‌‌long-bone‌‌growth‌ ‌
● GH‌‌stimulates‌‌all‌‌aspects‌‌of‌‌the‌‌processes‌‌of‌‌epiphyseal‌‌cartilage‌‌&‌‌long‌‌bone‌‌growth.‌‌GH‌‌stimulates‌‌osteoblasts‌‌to‌‌lay‌‌down‌‌more‌‌
new‌‌bone‌‌which‌‌leads‌‌to‌‌a‌‌thickening‌‌of‌‌the‌‌bone‌ ‌
● GH‌‌stimulates‌‌the‌‌liver‌‌to‌‌produce‌‌IGF-1,‌‌which‌‌will‌‌travel‌‌to‌‌the‌‌target‌‌site‌‌&‌‌is‌‌a‌‌major‌‌contributor‌‌to‌‌the‌‌production‌‌of‌‌cartilage‌‌&‌‌
bone‌ ‌
‌
Define‌‌the‌‌relationship‌‌b/w‌‌growth‌‌hormones‌‌&‌‌the‌‌insulin-like‌‌growth‌‌factor‌ ‌
● The‌‌liver‌‌produces‌‌&‌‌secretes‌‌IGF-1‌‌in‌‌response‌‌to‌‌GH‌‌stimulation‌ ‌
● IGF-1‌‌serves‌‌as‌‌a‌‌mediator‌‌for‌‌some‌‌of‌‌GH’s‌‌actions.‌‌A‌‌major‌‌target‌‌of‌‌IGF-1‌‌is‌‌the‌‌cartilage‌‌where‌‌IGF-1‌‌stimulates‌‌cell‌‌division‌‌&‌‌
growth‌ ‌
‌
Discuss‌‌how‌‌insulin-like‌‌growth‌‌factors‌‌can‌‌act‌‌in‌‌endocrine,‌‌autocrine‌‌&‌‌paracrine‌‌manner‌ ‌
● Endocrine:‌‌‌It‌‌is‌‌produced‌‌by‌‌the‌‌liver‌‌&‌‌can‌‌travel‌‌to‌‌other‌‌organs‌‌in‌‌the‌‌blood‌ ‌
● Autocrine:‌I‌t‌‌can‌‌be‌‌produced‌‌by‌‌the‌‌cells‌‌which‌‌require‌‌the‌‌IGF-1‌ ‌
● Paracrine:‌‌‌It‌‌can‌‌be‌‌produced‌‌in‌‌many‌‌cells‌‌&‌‌can‌‌act‌‌on‌‌the‌‌tissues‌‌in‌‌which‌‌it‌‌is‌‌produced‌ ‌
‌
Describe‌‌common‌‌pathologies‌‌associated‌‌w/‌‌inappropriate‌‌growth‌‌hormone‌‌secretion‌ ‌
● Gigantism:‌‌‌Excessive‌‌GH‌‌production‌ ‌
● Acromegaly:‌‌‌Excessive‌‌GH‌‌production‌‌after‌‌the‌‌epiphyseal‌‌discs‌‌have‌‌sealed‌‌(doesn’t‌‌cause‌‌↑‌‌in‌‌height,‌‌but‌‌↑ed‌‌growth‌‌of‌‌soft‌‌
tissues‌‌&‌‌coarsening‌‌of‌‌the‌‌skin)‌ ‌
● Dwarfism:‌‌‌Inadequate‌‌secretion‌‌of‌‌GH;‌‌target‌‌cells‌‌are‌‌insensitive‌‌to‌‌GH‌‌b/c‌‌of‌‌a‌‌mutation‌‌in‌‌the‌‌gene‌‌that‌‌codes‌‌for‌‌the‌‌GH‌‌receptor‌ ‌
‌
Identify‌‌the‌‌endocrine‌‌hormones‌‌secreted‌‌by‌‌the‌‌thyroid‌‌gland‌ ‌
● Thyroxine‌‌(T4)‌‌&‌‌triiodothyronine‌‌(T3)‌ ‌
‌
Discuss‌‌how‌‌thyroid‌‌hormone‌‌secretion‌‌is‌‌regulated‌ ‌
● Thyroid‌‌hormone‌‌secretion‌‌is‌‌regulated‌‌by‌‌thyroid‌‌stimulating‌‌hormone‌‌(TSH)‌‌&‌‌thyrotropin‌‌releasing‌‌hormone‌‌(TRH)‌ ‌
‌
Describe‌‌the‌‌microanatomy‌‌of‌‌the‌‌thyroid‌‌&‌‌formation‌‌by‌‌thyroglobulin‌ ‌
● The‌‌thyroid‌‌gland‌‌consists‌‌of‌‌numerous‌‌sacs‌‌called‌‌thyroid‌‌follicles.‌‌Each‌‌follicle‌‌consists‌‌of‌‌follicular‌‌cells‌‌surrounded‌‌by‌‌a‌‌fluid‌‌
(colloid)‌‌that‌‌contains‌‌thyroglobulin‌ ‌
‌
Discuss‌‌iodide‌‌trapping,‌‌organification‌‌&‌‌formation‌‌of‌‌T3‌‌&‌‌T4‌ ‌
Thyroid‌‌follicles‌‌accumulate‌‌Iodide‌‌from‌‌the‌‌blood‌‌&‌‌secrete‌‌it‌‌into‌‌the‌‌colloid.‌‌Once‌‌there,‌‌it‌‌is‌‌oxidized‌‌&‌‌attached‌‌to‌‌a‌‌tyrosine‌‌residue‌‌
within‌‌the‌‌protein,‌‌thyroglobulin‌‌(1‌‌iodine‌‌to‌‌tyrosine‌‌produces‌‌MIT,‌‌2‌‌iodine‌‌to‌‌tyrosine‌‌produces‌‌DIT).‌‌Within‌‌the‌‌colloid,‌‌enzymes‌‌modify‌‌
the‌‌structure‌‌of‌‌MIT‌‌&‌‌couple‌‌them‌‌together.‌‌(2‌‌DIT=‌‌T3‌‌or‌‌T4,‌‌1‌‌DIT‌‌&‌‌1‌‌MIT=T3).‌‌At‌‌this‌‌point,‌‌the‌‌T3‌‌or‌‌T4‌‌are‌‌still‌‌attached‌‌to‌‌the‌‌
thyroglobulin,‌‌until‌‌TSH‌‌is‌‌stimulated,‌‌where‌‌they‌‌are‌‌then‌‌hydrolyzed‌‌from‌‌thyroglobulin‌‌&‌‌are‌‌able‌‌to‌‌be‌‌secreted‌‌into‌‌the‌‌blood.‌ ‌
‌
Describe‌‌secretion‌‌of‌‌thyroid‌‌hormones‌ ‌
The‌‌thyroid‌‌hormones‌‌are‌‌stored‌‌in‌‌large‌‌quantities‌‌in‌‌the‌‌follicular‌‌fluid,‌‌enough‌‌for‌‌several‌‌months.‌ ‌Each‌‌thyroglobulin‌‌molecule‌‌will‌‌have‌‌
about‌‌30‌‌thyroxine‌‌molecules‌‌&‌‌a‌‌few‌‌triiodothyronine‌‌molecules.‌‌At‌‌the‌‌time‌‌of‌‌release‌‌the‌‌hormones‌‌are‌‌enzymatically‌‌split‌‌from‌‌the‌‌
thyroglobulin‌‌by‌‌proteases.‌‌The‌‌hormones‌‌diffuse‌‌through‌‌the‌‌base‌‌of‌‌the‌‌thyroid‌‌cell‌‌into‌‌the‌‌surrounding‌‌capillaries‌‌as‌‌free‌‌hormones.‌ ‌
‌
Identify‌‌&‌‌characterize‌‌conditions‌‌resulting‌‌in‌‌hyper-‌‌&‌‌hypo-‌‌secretion‌‌of‌‌thyroid‌‌hormones‌ ‌
Hyperthyroidism:‌‌‌autoimmune‌‌disorder,‌‌autoantibodies‌‌bind‌‌TSH‌‌receptors‌‌on‌‌thyroid‌‌gland‌‌follicular‌‌cells‌‌causing‌‌a‌‌growth‌‌of‌‌the‌‌thyroid‌‌
(goiter)‌‌&‌‌causes‌‌excessive‌‌secretion‌‌of‌‌the‌‌thyroid‌‌hormones.‌‌Grave’s‌‌disease‌‌is‌‌another‌‌hyperthyroid‌‌disease,‌‌&‌‌can‌‌cause‌‌symptoms‌‌such‌‌as‌‌
heat‌‌sensitivity,‌‌palpitations,‌‌bulging‌‌of‌‌the‌‌eyes,‌‌excessive‌‌perspiration‌‌etc.‌ ‌
Hypothyroidism:‌‌‌Deficiency‌‌in‌‌iodine‌‌in‌‌the‌‌diet‌‌can‌‌lead‌‌to‌‌a‌‌goiter‌‌(enlarged‌‌thyroid).‌‌Lack‌‌of‌‌iodine‌‌in‌‌the‌‌diet‌‌reduces‌‌the‌‌negative‌‌
feedback‌‌inhibition‌‌of‌‌TSH‌‌secretion,‌‌resulting‌‌in‌‌excessive‌‌secretion‌‌of‌‌TSH‌‌&‌‌stimulates‌‌the‌‌formation‌‌of‌‌an‌‌enlarged‌‌thyroid‌‌(goiter).‌‌
Symptoms‌‌include‌‌fatigue,‌‌impaired‌‌hair‌‌growth,‌‌intolerance‌‌to‌‌cold,‌‌dry‌‌skin,‌‌GI‌‌problems,‌‌depression‌‌&‌‌anxiety.‌ ‌
‌
Describe‌‌the‌‌physiological‌‌effects‌‌of‌‌thyroid‌‌hormones‌ ‌
● Excessive‌‌thyroid‌‌hormone‌‌secretion‌‌can‌‌cause‌‌someone‌‌to‌‌be‌‌nervous‌‌&‌‌emotional,‌‌impotence‌‌in‌‌males‌ ‌
●
Lack‌‌of‌‌thyroid‌‌hormones‌‌can‌‌lead‌‌to‌‌depression‌‌&‌‌anxiety,‌‌loss‌‌of‌‌libido‌ ‌
‌
Identify‌‌anatomical‌‌regions‌‌of‌‌ADH‌‌synthesis‌‌&‌‌secretion‌ ‌
● ADH‌‌is‌‌produced‌‌in‌‌neuron‌‌cell‌‌bodies‌‌of‌‌the‌‌supraoptic‌‌&‌‌paraventricular‌‌nuclei‌‌in‌‌the‌‌hypothalamus‌‌&‌‌secreted‌‌by‌‌the‌‌posterior‌‌
pituitary‌ ‌
‌
Discuss‌‌how‌‌secretion‌‌of‌‌ADH‌‌is‌‌regulated‌ ‌
● The‌‌secretion‌‌of‌‌ADH‌‌is‌‌controlled‌‌by‌‌neuroendocrine‌‌reflexes‌ ‌
● Secretion‌‌is‌‌stimulated‌‌by‌‌osmoreceptor‌‌neurons‌‌in‌‌the‌‌hypothalamus‌‌in‌‌response‌‌to‌‌a‌‌rise‌‌in‌‌plasma‌‌osmolality‌ ‌
● ADH‌‌secretion‌‌is‌‌inhibited‌‌by‌‌sensory‌‌input‌‌from‌‌stretch‌‌receptors‌‌in‌‌the‌‌left‌‌atrium‌‌of‌‌the‌‌heart‌‌which‌‌are‌‌stimulated‌‌when‌‌there‌‌is‌‌
a‌‌rise‌‌in‌‌blood‌‌volume‌ ‌
‌
Describe‌‌the‌‌effects‌‌of‌‌ADH‌‌on‌‌water‌‌reabsorption‌‌in‌‌the‌‌kidney‌ ‌
● ADH‌‌stimulates‌‌water‌‌retention‌‌in‌‌the‌‌kidneys‌‌so‌‌that‌‌less‌‌water‌‌is‌‌excreted‌‌in‌‌the‌‌urine‌ ‌
● When‌‌blood‌‌volume‌↑
‌ es,‌‌ADH‌‌is‌‌inhibited‌‌so‌‌water‌‌may‌‌be‌‌excreted‌‌in‌‌the‌‌urine‌ ‌
‌
Discuss‌‌the‌‌effect‌‌of‌‌ADH‌‌on‌‌peripheral‌‌blood‌‌vessels‌ ‌
● ADH‌‌causes‌‌contraction‌‌of‌‌the‌‌smooth‌‌muscles‌‌&‌‌constriction‌‌of‌‌blood‌‌vessels‌‌(vasoconstriction)‌‌to‌↑
‌ ‌‌blood‌‌pressure‌ ‌
● Conversely,‌‌ADH‌‌inhibition‌‌will‌‌lead‌‌to‌‌vasodilation‌ ‌
‌
Describe‌‌diabetes‌‌insipidus‌ ‌
● Diabetes‌‌insipidus‌‌is‌‌a‌‌deficiency‌‌of‌‌ADH,‌‌causing‌‌an‌↑
‌ ‌‌in‌‌the‌‌drinking‌‌of‌‌water‌
● Blood‌‌glucose‌‌levels‌‌are‌‌normal‌‌&‌‌there‌‌is‌‌no‌‌glucose‌‌in‌‌the‌‌urine‌ ‌
‌