Physiology: Endocrinology (Lecture-Based)

Front 1

hormone responsiveness vs sensitivity?

Back 1

responsiveness = max response at saturating dose
sensitivity = conc required to reach half max response

Front 2

which type of hormone has longest half life?

Back 2

thyroid (T4 ~6.5 days)

Front 3

are steroids stored to great extent in endocrine glands?

Back 3

no

Front 4

what hormones are released from post. pituitary gland?

Back 4

(made in HYPOTHALAMUS)
ADH and oxytocin

Front 5

what's ant. and post. pituitary derived from embryonically?

Back 5

ant: oral ectoderm
post: neuroectoderm

Front 6

what does oxytocin do?

Back 6

targets mammary glands and uterus
uterine contraction and lactation

Front 7

what are the 5 cell types in ant. pituitary?

Back 7

corticotroph (ACTH, MSH)
thyrotroph (TSH)
gonadotroph (LH, FSH)
somatotroph (GH)
lactotroph (prolactin)

Front 8

what's the effect of alpha-MSH (melanocyte stim. hormone/melantropin)

Back 8

stim. production of melanin by melanocytes in skin and hair;
in the brain affects appetite and sexual drives

Front 9

how are thyroid hormones regulated?

Back 9

hypothalamus TRH -> pituitary TSH -> follicle cells (T3, T4)

T3 negative feedback to ant. pituitary -> de. sensitivity to TRH (also neg feedback to de. TRH in hypo)

Front 10

what is TSI?

Back 10

thyroid stim. immunoglobin
binds to TSH receptors, long-acting -> hyperthyroidism
(implicated in Grave's disease)

Front 11

how are sex hormones regulated?

Back 11

hypothalamus GnRH -> pit. LH/FSH -> testes (testosterone) or ovaries (estrogen, progesterone) (all neg. feedback to inhibit both GnRH and LH/FSH

Front 12

what is ACTH?

Back 12

adrenocorticotrophic hormone
hypo CRH (corticotropin RH) -> pit. ACTH -> in. cortisol and androgens

cortisol neg. feedback to inhibit CRH

Front 13

what are the zones of adrenal gland?

Back 13

GFR, Medulla
G = glomerulosa
F = Fasciculata
R = Reticularis

Front 14

what hormones are produced in which zone of adrenal gland?

Back 14

Glomerulosa - Aldosterone
Fasculata - Cortisols
Reticularis - Androgens
Medulla - Catecholamines (75% cells for epi/25% for NE)

Front 15

what is the precursor of pregnenolone?

Back 15

cholesterol

Front 16

what is the precursor of progesterone?

Back 16

pregnenolone

Front 17

what is aldosterone derived from? (give pathway)

Back 17

chol -> pregnenolone -> (3b) progesterone ->-> (21b, 11b) Aldo

Front 18

what is cortisol derived from? (give pathway)

Back 18

chol -> preg -> (17a) 17a-OH-preg -> (3b) 17a-OH-progesterone ->-> (21b, 11b) cortisol

Front 19

what's DHEA derived from? (give pathway)

Back 19

chol -> preg -> (17a) 17a-OH-preg -> DHEA -> 3b -> testosterone -> estradiol

Front 20

what is the most common steroid synthesis deficiency?

Back 20

21b-hydroxylase def.
down: cortisols, aldo,
up: sex hormones

Front 21

are glucocorticoids pro-inflammatory?

Back 21

no, they increase production of anti-inflammatory cytokines and impair cell-mediated immunity

Front 22

what are some effects of glucocorticoids?

Back 22

degrade mm. proteins -> muscle wasting
anti-insulin actions -> diabetes prone
fat mobilization -> weight gain ++

Front 23

what is Addison's disease?

Back 23

adrenal deficiency

Front 24

what is the sequence of events leading to puberty?

Back 24

adrenarche, gonadarche, in. pituitary sensitivity, in. gonadal sensitivity

Front 25

what is the pattern of gonadotropin release during puberty

Back 25

pulsitile GnRH relse during sleep -> LH -> gonad mature -> sex hormones

Front 26

what is the sequence of events for puberty for girls? for boys?

Back 26

girls: breast -> height -> pubic hair -> menarche
boys: testes -> pubic hair -> penis -> height

Front 27

is premature thelarche physiologic?

yuika: what do you mean by premature? ...do you mean pre-puberty?

Back 27

(early development of breasts without other signs) Yes. so is adrenarche (usually shown as growth of pubic hair)

Front 28

what are the two forms of sexual precocity?

Back 28

complete (gonadotropin dependent)
incomplete (gonadotropin independent) -> showing isolated signs of puberty but not others

Front 29

what is the role of leptin in puberty?

Back 29

critical weight/fat mass must be achieved for onset of puberty.
leptin made by adipocytes, stimulates GnRH and adrenal;
leptin def: obesity, gonadotropin def.

Front 30

how is the male sex determined?

Back 30

XY -> SRY -> testes ->
1. sertoli -> AMH -> mullerian duct regressions
2. leydig -> testosterone ->
a) AR -> stabilize Wolffian duct
b) (5alpha reductase) -> DHT -> AR -> differentiation of external genitalia
hCG/LH stim. Leydig.

Front 31

early maturation of zona reticularis causes what?

Back 31

premature adrenarche (public/axillary hair w/o other signs of puberty)

Front 32

what are the androgens?

Back 32

testosterone, dihydrotestosteron, androstenedione
potency: DHT>T>A

Front 33

what is the earliest endocrine gland to develop?

Back 33

thyroid

Front 34

embryonic migration of thyroid requires what?

Back 34

migration factor TTF-1

Front 35

what are the steps of thyroid hormone production?

Back 35

1. iodide uptake
2. organification (I- + thyroperoxidase -> I)
3 incorporation to tyrosine (on thyroglobulin, colloid cells matrix) -> MIT
4. MIT + I -> DIT x2 -> T4
5. T4 + deiodinase -> T3/rev T3 -> T2

(only T3 biologically active)

Front 36

what mediates iodide uptake?

Back 36

NIS (Na+/I- symporter) on basolateral surface of thyroid follicles

Front 37

how is iodide uptake regulated?

Back 37

TSH in. iodide transport;
perchlorate (ClO4-) and thiocyante inhibits iodide transport;

Front 38

what is the action of TSH on T3/T4?

Back 38

TSH causes release of T3/T4 from thyroglobulin -> MIT/DIT deiodinated to release iodine for recycling.

Front 39

how is the release of thyroid hormones regulated?

Back 39

hyp. TRH -> pit. TSH -> thy T3/T4 (neg feedback to inhibit both TRH/TSH)

Front 40

T3/4 in circulation bound to what?

Back 40

~70% to thy. hormone binding globulin (TBG)
some to albumin and transthyretin
T4 more tightly bound -> longer half life

Front 41

what is the mechanism of action for T3?

Back 41

diffuse into cell, bind to THR, displaces co-repressor on THR (bound to RXR in complex) on TRE on DNA, recruits activator -> activate txn.

Front 42

what are the effects of thyroid hormones?

Back 42

1. bone growth
2. CNS maturation
3. b-adrenergic effects
4. increase basal metabolic rate (in. body temp, O2 consumption etc)
5. increase glycogenolysis, lipolysis, gluconeogenesis
6. increase CO, HR, SV, contractility, RR

Front 43

Rathke's pouch (pituitary) gives rise to what?

Back 43

Corticotrop and alpha-subunit

Front 44

alpha-subunit derived from Rathke's (pituitary) gives rise to what?

Back 44

thyrotroph (TSH) and gonadotroph (LH/FSH)
also gives rise to Pit-1, which is precursor to lactotroph (prolactin), thyrotroph and somatotroph (GH)

Front 45

what is Prop-1?

Back 45

enz involved in converting alpha-subunit to Pit-1; also a-subunit to gonadotroph

Front 46

give the hypothalamus-pituitary-GH axis

Back 46

hypo GHRH -> pit GH -> IGF-1
both GH and IGF-1 neg feedback

Front 47

what are the effects of GH?

Back 47

major: in. IGF-1 production
also: metabolic effect on adipose tissue (lipolysis, de. gluc uptake) and mm. (in. gluc uptake, in. protein synthesis)

Front 48

what are the effects of IGF-1?

Back 48

major: bone growth, also stim mm growth

Front 49

what is the signaling pathway for GHRH in somatotroph

Back 49

GHRH binids GHRH-R (membrane-G-protein) -> cAMP -> PKA -> CREB -> in. Pit-1 -> in. GHRH-R and also GH txn.

Front 50

(T/F) growth hormone secretion is pulsitile

Back 50

TRUE (hence cannot just take one measurement for clinical evaluation)

Front 51

(T/F) growth hormone receptor is a membrane receptor

Back 51

TRUE

Front 52

(T/F) growth hormone binding protein is made from part of the GH receptor

Back 52

TRUE

Front 53

(T/F) IGF-1 is required only for prenatal growth but not postnatal growth

Back 53

FALSE. IGF-1 is required for both pre and postnatal growth

Front 54

(T/F) IGF-1 production is dependent on GH both pre- and postnatally

Back 54

FALSE. Prenatal IGF-1 is GH-independent. Postnatal IGF-1 is GH-dep.

Front 55

(T/F) IGF-1 binds insulin receptor

Back 55

affinity: IGF-1R > insulin R
(+++ IGF-1 -> hypoglycemia)

Front 56

(T/F) IGF-2 is important for both fetal and postnatal growth?

Back 56

False. IGF-2 is most important for fetal growth. Postnatal effect unknown.

Front 57

(T/F) IGF-2 binds both IGF-2R and IGF-1R

Back 57

TRUE. Action through 1R, 2R mediates IGF-2 clearance.

Front 58

What are the major hormones and factors that affect growth?

Back 58

GH (IGF-1), thyroid hormones, sex steroids, growth factors (FGF family), nutrition, genetics

Front 59

what mutation causes achondroplasia (short statue)

Back 59

mutation in FGFR3

Front 60

(T/F) Prenatal growth in height precedes growth in weight

Back 60

TRUE (hence premature babies are long but thin)

Front 61

Describe parental imprinting on growth (paternal vs maternal)

Back 61

paternal imprinting promotes growth
maternal imprinting retards growth

Front 62

What is Beckwidth-Wiedemann Syndrome?

Back 62

fetal overgrowth, due to
1) duplication of paternal IGF-2 gene or
2) loss of maternal imprinting of IGF-2

Front 63

what is Russell-Silver Syndrome?

Back 63

imprinting abnormality; poor pre- and postnatal growth

Front 64

What is the Barker hypothesis (Fetal programming and adult diseases)

Back 64

maternal undernutrition -> fetal growth retardation -> structural change with organ -> poor childhood growth, disease in later life, metabolic & endocrine dysfunction

Front 65

what's mid-parent height?

Back 65

80% children reach MPH:
Boys: (Dad's H + (Mom's H + 5))/2
Girls: ((DH - 5) + MH)/2

Front 66

choose one: intrinsic shortness, delayed growth, attenuated growth:

bone age = chronological age, normal growth rate

Back 66

intrinsinc shortness

Front 67

choose one: intrinsic shortness, delayed growth, attenuated growth:

bone age = height age, normal growth rate

Back 67

delayed (constitutional delay, undernutrition, chronic disease etc)

Front 68

choose one: intrinsic shortness, delayed growth, attenuated growth:

bone age = height age, slow growth rate

Back 68

attenuated (endocrinopathy, chronic disease, metabolic disorder etc)

Front 69

what are growth-hormone stimulation test

Back 69

(pulsitile!)
Physiological - sleep, exercise, fasting
Pharma - glucagon, arginine, pronanolol, L-dopa, insulin-induced hypoglycemia

Front 70

choose one: primary hyperparathyroidism, secondary hyperparathyroidism, hypercalcemia of malignancy, hypoparathyroidism:
high serum [Ca], high [PTH]

Back 70

primary hyperPT (overproduction of PTH)

Front 71

choose one: primary hyperparathyroidism, secondary hyperparathyroidism, hypercalcemia of malignancy, hypoparathyroidism:
high serum [Ca], low [PTH]

Back 71

hypercalcemia of malignancy (something is overproducing Ca, e.g. bone cancer)

Front 72

choose one: primary hyperparathyroidism, secondary hyperparathyroidism, hypercalcemia of malignancy, hypoparathyroidism:
low serum [Ca], low [PTH]

Back 72

hypoPT (not enough PTH production); may be caused by activating mutation in Ca sensing receptor, or intrinsic PT disorder.

Front 73

choose one: primary hyperparathyroidism, secondary hyperparathyroidism, hypercalcemia of malignancy, hypoparathyroidism:
low serum [Ca], high [PTH]

Back 73

secondary hyperPT
(usually caused by renal failure -> unable to produce vit. D in response to PTH -> more PTH produced in attempt to rectify problem, but Ca stays low.)

Front 74

(T/F) Ca sensing R also recognizes divalent cations e.g. Mg++

Back 74

True, but with reduced affinity

Front 75

What class of receptor is Ca sensing receptor?

Back 75

receptor G-protein (7-membrane spanning)

Front 76

where are Ca sensing receptors founds?

Back 76

thyroid C cells (produces calcitonin), renal tubules (TAL), parathyroid chief cells.

Front 77

what is the signaling pathway of Ca sensing receptors in parathyroid cells?

Back 77

extracellular Ca -> activate Gq and Gi -> de. cAMP, + PKC -> kinases -> PTH DEGRADATION -> de. PTH release

Front 78

what secrets PTH?

Back 78

chief cells of PT (4 altogether)

Front 79

(T/F) All PTH secreted is suppressible and Ca-dependent

Back 79

FALSE. 15% non suppressible and not dependent on Ca conc.

Front 80

Name two disorders caused by inactivating mutations of Ca sensing receptors

Back 80

Heterozygous:
Familial hypocalciuric hypercalcemia (FHH): low urine Ca, high PTH, high serum Ca. BENIGN condition (often misdiagnosed as hyperparathyroidism leading to unnecessary excision of PT)

homozygous: severe prenatal hypercalcemia -> FATAL

Front 81

Name one disorder caused by ACTIVATING mutations of Ca sensing receptors

Back 81

familial hypocalciuric hypocalcemia = hypoparathyroidism

Front 82

what is the name of the connective tissue surrounding the bone?

Back 82

periosteum

Front 83

what are the differences between woven bone and lamellar bone?

Back 83

woven: random organization, weaker, deposited rapidly (fetal bone and callus formation)
lamellar: all adult bones (trabecular and compact), stronger, parallel organization, slowly deposited

Front 84

(T/F) osteoblasts are multinuclear giant cells

Back 84

FALSE. osteoCLAST are multinuclear

Front 85

what do osteoblasts and osteoclasts do?

Back 85

Blasts: form bone, secret type I collagen to form bone matrix, stim. osteoclast maturation

clasts: secrets HCl to dissolve bone for resorption

Front 86

what are bone-lining cells and osteocytes?

Back 86

bone lining: resting osteoblasts on bone surface

osteocytes: retired osteoblasts within bone matrix, important for mechanotransduction.

Front 87

What are RANK and RANKL?

Back 87

RANKL - on surface osteoblasts, ligand for RANK

RANK - on osteoclast precursor, binding to RANKL enables maturation of precursor OC.

Front 88

what are the four major disorders of bone remodeling?

Back 88

1. osteosporosis: resorption > formation (low bone mass, but matrix:mineral ratio normal)
2. osteopetrosis: defective resorption (hard but brittle bone)
3. osteomalacia: defective mineralization (vit D def, lack Ca/Phos, normal to high matrix)
4. Paget's disease - disorganized, excessive resorption and formation (may be caused by viral infections)

Front 89

what are two common causes of osteosporosis?

Back 89

1. excessive resorption: post-menopausal women (cos estrogen important for OB/OC regulation

2. reduced formation (glucocorticoids)

(matrix to mineral ratio normal)

Front 90

where is the central appetite regulation center?

Back 90

hypothalamus (arcuate nucleus - ARC)

Front 91

what are the anorexigenic neuropeptides?

Back 91

made in ARC: aMSH, CART (cocaine/amphetamine regulated transcript)
others: seratonin (5-TH), CRH

Front 92

what are the orexigenic neuropeptides?

Back 92

made in ARC: AgRP (Agouti related protein), neuropeptide Y (ends in tyr, Y, hence name)
others: opioids, orexins, MCH (melanin-concentrating hormone)

Front 93

what is the effect of AgRP?

Back 93

1. blocks aMSH at MC4
2. antagonist for MC3/4 receptors

Front 94

What is POMC?

Back 94

pro-opiomelanocortin, pro-hormone that includes transcripts for:
1. aMSH (made in pars intermedia)
2. ACTH (made in ant. pituitary)
3. b-endorphins (pain relieve, euphoric effects, may in. appetite)

Front 95

what receptors does ACTH act on?

Back 95

MC2, stim. adrenal glands

Front 96

what are the effects of aMSH?

Back 96

on MC1 R: increase pigmentation of melanocytes
on MC3/4 R: decrease food intake

Front 97

what is secreted along with POMC in ARC?

Back 97

CART

Front 98

what is ghrelin?

Back 98

GI hormone. High when starved, low after meal.
binds to GH-secretagogue R -> in. GH release
increase hunger.

Front 99

what GI hormones inhibit appetite after meal?

Back 99

CCK (prox small bowel)
GLP-1 (distal small bowel)
insulin (pancreas b cells)
PYY (colon)

Front 100

what other factors induces satiety (besides GI hormones)?

Back 100

1. mechanical signals (gut distention, nutrient transit) vagus -> CNS
2. nutrients/metabolites (e.g. glucose)

Front 101

what relays GI satiety signals to the hypothalamus?

Back 101

nucleus tractus solitaris (NTS) and area postrema in brainstem.

Front 102

what txn factor is required for maturation of adipocytes?

Back 102

PPAR-gamma: stromal cells to mature adipocytes
(cortisol is also required for lipogenesis and fat accumulation)

Front 103

where can you find the highest number of receptors for leptin?

Back 103

hypothalamus

Front 104

where is leptin made?

Back 104

adipocytes

Front 105

what is the effect of leptin?

Back 105

crosses BBB to reach hypothalamus, + secretion of POMC/CART;
- secretion of AgRP/NPY
(decrease food intake)
leptin low when starved

Front 106

why doesn't high leptin levels help in some obese patients?

Back 106

they've developed resistance to leptin.

Front 107

t/f there isn't a correlation bw BMI and Type II diabetes

Back 107

False!

Front 108

how do you describe those neurotransmitters/neuropeptides that stimulate feeding?

Back 108

orexigenic

Front 109

how do you describe those neurotransmitters/neuropeptides that inhibit feeding?

Back 109

anorexigenic

Front 110

t/f leptin inhibits orexigenic neurons

Back 110

true

Front 111

t/f leptin inhibits anorexigenic neurons?

Back 111

false

Front 112

t/f AgRP is an antagonist of one of alpha-MSH's receptors (MC3/MC4)

Back 112

true

Front 113

what does ghrelin do?

Back 113

-Acts on hypothalamus to increase hunger

-appears to stimulate food intake in the short temr

(low ghrelin after mean, high during fasting)

Front 114

hhow do you gain fat mass?

Back 114

1) adipocyte hypertrophy (inc cell mass)

2) adipocyte hyperplasia (inc cell #)

Front 115

As adipocytes increase in size/number – they produce more ________

Back 115

leptin

Front 116

t/f leptin deficiency is a common of cause human obesity

Back 116

false! leptin def only accounts for a small percentage of obesity in human

Front 117

t/f the resting + total energy expenditure of obese people is > than lean people

Back 117

true

Front 118

t/f sympathetic n system inhibits lipolysis & decreases total and basal oxygen consumption

Back 118

False

sympathetic n system stimulates lipolysis & increases total and basal oxygen consumption

Front 119

t/f the thyroid hormone axis is responsible for up to 30% of Resting Energy Expenditure (REE)

Back 119

true

Front 120

list the 4 different types of cells in the islet of Langerhan (pancreas)

Back 120

alpha - glucagon (20%)
beta - insulin (70%)
delta - somatostatin (5%)
gamma - pancreatic peptides (rare)

Front 121

what is packaged with insulin into secretory vesicles in the Golgi?

Back 121

c-peptide (cleaved from pro-insulin)
pre-proinsulin -> pro-insulin -> insulin (alpha and beta chain joined by disulfide bonds)

Front 122

(t/f) skeletal mm. accounts for ~90% of glucose disposal at high insulin conc

Back 122

true

Front 123

how is glucose sensed by beta cells?

Back 123

glut2 -> gluc into cytosol -> produce ATP -> ATP-sensitive K+ channels (Kir6.2 + SUR1) -> depol -> opens Ca++ channels -> inc. [Ca] in cytosol triggers release of insulin granules

Front 124

how is insulin sensed in target cells?

Back 124

through insulin receptor (intracellular substrate IRS-1 becomes phosphorylated upon insulin binding -> triggers series of gene txn to inc. glucose transporter, lipogenesis, glucose storage etc)

Front 125

how does adrenaline affect insulin and glucagon levels?

Back 125

inc. glucagon, dec insulin

Front 126

what hormones stimulates insulin release?

Back 126

glucagon, GI peptides, GH, TSH, ACTH

Front 127

does parasympathetics increase or decrease insulin?

Back 127

increase; sympathetics decreases
(cf glucagon is increased by both parasymp and symp)

Front 128

what inhibits glucagon production?

Back 128

insulin and somatostatin
(somatostatin also inhibits insulin)

Front 129

what's normal glycemia?

Back 129

FPG: <100 mg/dL (diabetes: >126)
2-hr PG: <140 mg/dL (diabetes: >200)

Front 130

what are the differences between type I and type II diabetes?

Back 130

I: IDDM, autoimmune destruction of beta cells, prone to ketoacidosis, childhoood onset
II: NIDDM, dec. sensitivity to insulin, not prone to KA but can happen, inc. or normal serum insulin, obesity

Front 131

what does insulin deficiency cause?

Back 131

inc. plasma glucose -> hyperglycemia -> osmotic diuresis -> lost of electrolytes -> dehydration
inc. protein breakdown -> inc. a.a. -> inc. gluconeogenesis -> same as above
inc. lipolysis -> inc. free fatty acids -> ketogenesis -> ketouria and acidosis (also inc. glycerol -> inc. gluconeogenesis -> same as above)