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Physiology > Endocrine > Flashcards

Endocrine Flashcards

1
Q

Specificity vs. Affinity in Hormone Receptor Binding

A

SPECIFICITY: ability to distinguish between similar substances (at what [ ] must the substance be before the receptor is activated)

AFFINITY:
determined by Kd –> ligand [ ] that occupies 50% of binding sites (smaller Kd = higher affinity). ‘

Ki is also associated –> [ ] that a hormone must be at before it kicks off 50% of another ligand

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2
Q

Rate limiting step of catecholamine formation

A

Tyrosine Hydroxylase conversion of Tyrosine to XDOPA

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3
Q

Function of Dopamine

A

Tonic Inhibitor of prolactin release from anterior pituitary

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4
Q

Defining component of Catecholamines and the main type(s).

A

Derived from single tyrosine

-Dopamine, Epi, NE

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5
Q

Defining component of Indoleamines and the main type(s)

A

Derived from single tryptophan

-Serotonin is the main one (and melatonin comes from serotonin)

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6
Q

Rate limiting step of indoleamine formation

A

Tryptophan hydroxylase conversion of Tryptophan to an intermediate

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7
Q

Function of serotonin and where it is made.

A

95% made in gut. Acts as a vasoconstrictor and stimulates smooth muscle cell contraction in intestine.

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8
Q

Melatonin (formation, uses and consequences)

A

Formation: converted from serotonin in the pineal; N-acetyltransferase is the RLS

Function: Regulation of day and night cycles. Used therapeutically for variety of conditions including insomnia, jet lag, SAD, migraines, etc. Active only during night.

Potent inhibitor of male reproductive functions

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9
Q

Basics of biosynthetic processing of steroid hormones

A

StAR protein transports free cholesterol from outer to inner mitochondria where it is converted to pregnenolone by cytochrome P450scc desmolase. Pregnenolone is subsequently converted to the glucocorticoids, mineralcorticoids, androgens and estrogens.

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10
Q

PVN

A

Paraventricular Nucleus

CRH, TRH (anterior pit); AVP, OXY (posterior pit)

Thirst, BP, mood/emotion/stress

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11
Q

POA

A

Preoptic Nucleus

GnRH

Reproduction

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12
Q

ARC

A

Arcuate Nucleus

Growth Hormone Releasing Hormone (GHRH)

Feeding behavior, satiety

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13
Q

SCN

A

Suprachiasmatic Nucleus

Sleep, Circadian Rhythms

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14
Q

ME

A

Medial Eminence

Functional converging point for neurons of hypothalamus, where they all release their hormones

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15
Q

GnRH pulsatility every 30 -60 mins favors…

every 2-3hrs…?

A

30-60mins: LH

2-3hrs: FSH

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16
Q

Tuberoinfundibular System

A

Anterior Pituitary

Comprises all neurons that send axonal projections to the median eminence. Hormones target the anterior pituitary through the capillary system (endocrine).

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17
Q

Neurohypophysial Tract

A

Posterior Pituitary

Comprises neurons whose axons terminate in the posterior pituitary.

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18
Q

Major cell types of the anterior pituitary and what they secrete.

A

ACIDOPHILS (most abundant):
Somatotrophs (GH)
Lactotrophs (prolactin)

BASOPHILS:
Corticotrophs (ACTH)
Gonadotrophs (LH/FSH)
Thyrotrophs (TSH)

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19
Q

What composes 90% of the Anterior Pituitary?

A

Pars distalis

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20
Q

Herring Bodies

A

Dilations of unmyelinated axons near the terminals which serve as the site of hormone release for the POSTERIOR PITUITARY.

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21
Q

Prolactin vs Oxytocin

A

Prolactin: Milk production, mammory gland development and breast differentiation
Oxytocin: Milk ejection

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22
Q

Carrier for AVP? For Oxytocin?

A

AVP- neurophysin II

Oxy- neurophysin I

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23
Q

ADH is secreted from what cells?

A

Magnocellular (posterior pit): fluid balance

Paracellular (median eminence): stress/anxiety

Both are cells of the PVN

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24
Q

What does AVP bind to?

A

V1 RECEPTORS: vascular smooth muscle cells, producing contraction and increased vascular resistance

V2 RECEPTORS: distal collecting duct for AQP2 channel insertion and formation

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25
Q

Specific cell for release of oxytocin

A

Magnocellular neurons whose cells are located in PVN

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26
Q

Somatostatin

A

Inhibits pulsatile frequency of GHRH and thus blocks GH and TSH release from pituitary.

Also suppresses insulin release

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27
Q

GH Direct effects vs IGF-1 effects

A

GH Direct: (1) promotes lean body mass (increased protein and decreases adiposity). (2) Increases plasma glucose levels.

IGF-1 (GH Indirect): stimulates cellular proliferation in visceral organs and bone/cartilage growth. INSULIN DEPENDENT

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28
Q

Gigantism vs. Acromegaly

A

Both caused by GH Excess

GIGANTISM: GH excess before closing of epiphyseal plate in childhood. Increases long bone growth resulting in extreme height.

ACROMEGALY: Usually diagnosed in middle age and most often caused by pituitary adenoma. Gradual enlargement of hands/feet. Widening of face, protruding jaw, enlarged lips, tongue, nose and brow.

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29
Q

Types of Dwarfism

A

Both are GH deficiencies first established in childhood.

LARON SYNDROME: GH receptor doesn’t work (genetic defect). (1) no production of IGF-1 (2) Plasma levels are normal to high (loss of feedback)

AFRICAN PYGMY: partial defect in GH receptor so no pubertal increase in IGF-1. not noticed until puberty so tough to reverse. Normal plasma GH

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30
Q

Adult GH deficiency

A

(1) Caused by tumor/surgery or treatment
(2) increased fat deposition
(3) reduced bone density
(4) High LDL/TGs

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31
Q

Prolactin stimulation

A

Mainly by TRH (Thyrotropin-releasing hormone) and also oxytocin

Produced by hypothalamus to stimulate release of TSH and prolactin from anterior pituitary.

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32
Q

Prolactin inhibits release of what hormone?

A

GnRH –> which is why breast feeding moms don’t easily get pregnant.

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33
Q

CRH binds with highest affinity to what receptor?

A

CRH R1 in anterior pituitary to activate G-protein induced PKA pathway

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34
Q

What two hormones act synergistically to increase amplitude of ACTH release from the anterior pituitary?

A
  • AVP

- CRH

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35
Q

Preprohormone of ACTH

A

POMC gene

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36
Q

Main ACTH action in adrenal gland

A

Stimulate biosynthesis of glucocorticoids

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37
Q

ACTH receptor

A

MC2R –> high affinity

MC1R –> low affinity (found in skin, causes hyper-pigmentation with high levels of ACTH)

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38
Q

Adrenal gland secretions by layer

A

Z. GLOMERULOSA: mineralocorticoids
Z. FASCICULATA: glucorticoids (cortisol)
Z. RETICULARIS: weak androgens (DHEA)

MEDULLA: catecholamines

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39
Q

Cortisol transport

A

CBG (corticosteroid binding globulin). Used to transport 90% of circulating cortisol in the blood.

Decreased by estrogen or shock/severe infection

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40
Q

Enzyme that converts cortisone to cortisol and what happens next

A

11B-HSD-1; Cortisol binds to intracellular GR receptor (after displacement of chaperone on GRR). This complex enters cell for transcription purposes.

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41
Q

Functions of Cortisol

A

I Got Caught With A Fancy B.M.W.

I: immunity/inflammation (Decreased)
G: Glucose (Increase)
C: Connective Tissue (Decrease)
W: Water clearance and GFR (Increase)
A: Arteriole tone (Increase)
F: Fetal maturation (Increased)
B: Bone (degradation)
M: Muscle Mass (decrease)
W: Wakefulness and emotional state
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42
Q

How does Cortisol increase muscle breakdown

A

FoxO transcription factor regulation which stimulates expression of E3 ubiquitin ligase and MuRF-1 which lead to protein degradation.

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43
Q

How does Cortisol increase fat breakdown and redistribution

A

MAG lipase and Hormone sensitive lipase (HSL)

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44
Q

How does Cortisol block immune function and nflammatory action?

A
  • stimulates anti-inflammatory cytokines
  • inhibits prostaglandins
  • suppresses antibody production
  • increases neutrophils, platelets and RBCs but blocks their function
  • stimulates IkB (which binds NFkB) and binds directly to block NFkB
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45
Q

Cushing disease vs syndrome

What are their effects?

A

DISEASE: Excessive cortisol secretion due to pituitary adenoma

SYNDROME: Any other reason for excessive cortisol secretion

EFFECTS:

  • purple stria
  • change in body fat distribution (moon face, skinny arms, large abdomen)
  • osteoporosis
  • hypertension
  • glucose intolerance
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46
Q

Addison’s disease

A

Autoimmune destruction of adrenals

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47
Q

Mineralocorticoids

A

Hormones that promote sodium retention by the kidney. Water retention = secondary result.

ALDOSTERONE –> main mineralocorticoid

48
Q

Aldosterone main function/targets

A

Stimulate sodium and water reabsorption in the kidney; increases potassium secretion.

Mineralocorticoid Receptor is highly expressed in following:

  • Kidney (distal tubule)
  • Colon
  • Salivary ducts
  • Sweat ducts
49
Q

Activation and inactivation of cortisol

A

inactivated to cortisone by 11B-HSD2 (occurs in MR. flows freely back into the blood)

Activated by 11B-HSD1 (can be used by GR)

50
Q

Licorice and sodium/water retention

A

Increased licorice = inhibition of 11B-HSD2 = increased cortisol levels = cortisol activation of MR = increased sodium and water retention

51
Q

DHEA

A

Precursor for testosterone and estrogens

52
Q

Universal first step of steroid hormone biosynthesis

A

Conversion of cholesterol to pregnenolone via CYP11A1 side-chain removal

53
Q

Congenital Adrenal Hyperplasia

A

Loss of ability to make certain vital hormones, often cortisol.

Caused by:

(1) 21-a hydroxylase deficiency: excess DHEA, no mineralocorticoids or glucocorticoids
(2) 11-B hydroxylase deficiency: salt and water retention due to excess in mineralocorticoids

54
Q

Major cell type of the adrenal medulla and what causes its secretions

A

Chromaffin cells.

Stimulated to secrete catecholamines via spinal cord

55
Q

Function of cortisol on NE

A

Cortisol stimulates conversion of NE to Epi, in the adrenal medulla

56
Q

What works to degrade catecholamines?

A

COMT and MAO

57
Q

Metabolic by-product of catecholamine degradation and its use.

A

Vanillymandelic acid (VMA)– secreted in urine and can be used clinically to detect tumors producing excess EPI or NE.

58
Q

Pheochromocytoma

A

tumor originating from chromaffin cells, causing overproduction of catecholamines

Also known as “The 10% Tumor”:
10% of these tumors are…

malignant, bilateral, in children, familial, recurring, associated with endocrine tumors, present with stroke or are extra-adrenal

59
Q

Main cellular components of thyroid

A

FOLLICLE:

  • epithelial cells surrounding lumen
  • lumen filled with colloid; major component is T3/T4 and thyroglobulin

PARAFOLLICULAR CELLS (“C” CELLS):

  • produce calcitonin
  • no contact with the colloid

OTHER:
-epithelial cells, fibroblasts, lymphocytes, adipocytes

60
Q

Two precursors needed for thyroid hormone formation

A

Thyroglobulin (TG) and iodide

61
Q

Minimum iodide intake for thyroid deficiency

A

20 ug/day (400 ug/day is average in U.S.)

62
Q

Wolf-Chaikoff effect

A

Assures constancy of iodide storage in face of changes in dietary iodide.

Increases in iodide intake decrease gland transport and hormone synthesis. Clinically, very high iodide doses –> rapid thyroid shutdown.

63
Q

Type I deiodinase

Type II deiodinase

Type III deiodinase

A

All convert T4 to T3 (or rT3)

I: primary source of T3 in circulation. liver, kidney, thyroid, skeletal.

II (MOST CRITICAL): peripherally deiodinates T4 to T3 in brain, pituitary, placenta and in the heart. Also acts as a THYROID HORMONE SENSOR.

III: only makes reverse T3 (no biological activity)

64
Q

Inhibition of TSH release

A

Negative feedback of T3. Also Dopamine and somatostatin function tonically inhibit TSH function.

65
Q

Steps of Thyroid Hormone Synthesis

A

(1) Iodide trapping
(2) Transport- Iodide transported to lumen and oxidized to iodine. Thyroglobulin transported to lumen
(3) Iodination of MIT/DIT onto thyroglobulin
(4) Conjugation to for T3/T4
(5) Endocytosis
(6) Proteolysis to release everything from vesicle
(7) secretion of T3/T4

66
Q

Carbimazole (methimazole)

A

Inhibits thyroid peroxidase. Used as treatment for hyperthyroidism because iodide can no longer become iodine

67
Q

NIS

A

Sodium iodide symporter which brings iodide into thyroid

68
Q

Cold vs Hot spot

A

Seen during thyroid autoradiographs.

Cold = white spot surrounded by black = cancer
Hot= black spot surrounded by white = hyperthyroidism
69
Q

Organification defect

A

Iodide cannot be incorporated into tyrosine

70
Q

THR

A

Thyroid hormone receptor

Internal. Member of the nuclear receptor superfamily. Heterodimerizes with retinoic acid receptor (RXR) upon ligand binding and then this THR:RXR complex assists in transcriptional activation.

Almost every cell type has THR

71
Q

T3 and the CNS

A

T3 is critical for normal brain development.

  • neuronal cell migration/differentiation
  • myelination
  • synaptic transmission
72
Q

Grave’s disease

A

Hyperthyroid

Autoimmune antibodies stimulate TSH via Long-acting thyroid stimulator (LATS)

Elevated T3/T4

73
Q

Hashimoto’s Thyroiditis

A

Hypothyroid

Autoimmune destruction of thyroid follicles.

Antibodies against TPO (thyroid peroxidase) , TG (thyroglobulin)

74
Q

Thyroid Storm + treatment

A

Hyperthyroid coupled with severe acute illness

Could cause altered mental status and severe circulatory collapse leading to death.

TREATMENT: only acute treatment = PTU; carbimazole; beta blockers for heart function

75
Q

What cells secrete PTH

A

The chief cells of the parathyroid gland

76
Q

Osteoclasts and PTH

A

KEY CONCEPT

Osteoclasts do not have any receptors for PTH so stimulation is indirect. PTH stimulate macrophage colony-stimulating factor (M-CSF) in osteoblasts, which stimulates differentiation of osteoclast precursors.

PTH also stimulates RANK-L which leads to maturation of osteoclast and bone reabsorption.

77
Q

OPG

A

Osteoprotegrin

Antagonist of RANK-L (and therefore is anti-bone breakdown). Works as RANK-L receptor decoy.

Stimulated by estrogens; inhibited by glucocorticoids

78
Q

Function of PTH in Kidney

A

(1) stimulates Ca2+ reabsorption
(2) reduces phosphate reabsorption
(3) stimulates conversion of active form of Vit D via stimulation of CYP1a gene transcription

79
Q

PTH Regulation

A

(1) Calcium-sensing receptor (CaSR). Binds ionized Ca2+. Inhibits PTH synthesis/stimulates its degradation. Located in PT chief cells, kidney tubules and C cells.
(2) Vit D. Inhibits PTH synthesis and stimulates CaSR.

80
Q

Calciferol

A

General term for Vit D

81
Q

Calcidiol

A

Aka Calcifidiol or 25-hydroxyvitamin D. Immediate precursor to active Vit D.

Formed in liver.

82
Q

Calcitriol

A

Aka calcifitriol or 1, 25-dihydroxyvitamin D. Active form of Vit D.

1a-hydroxylase is the key enzyme for its formation

Formed in kidneys.

83
Q

Vit D functions

A
  • Some mobilization of Ca2+ from bone/ bone proliferation and differentiation.
  • Increases Ca2+ (via TRPV5/6, calbindin and a Ca2+ ATPase pump for the Ca2+ reabsorption) and phosphate (via Na+-Pi cotransporter)
84
Q

Primary vs Secondary Hyperparathyroidism

A

PRIMARY: caused by hyperplasia or carcinoma of parathyroid

SECONDARY: due to chronic renal failure which blocks active Vit D synthesis and therefore inhibition of PTH

Both cause hypercalcemia and kidney stones

85
Q

Signs of hypoparathyroidism

A

Chvostek sign: twitching of facial muscles in response to tapping of facial nerve

86
Q

Paget disease

A
  • Excessive localized regions of bone resorption and reactive sclerosis.
  • Calcitonin may be of some use in its treatment
87
Q

Cell types of the pancreas and their functions

A

(1) Beta cells [75% of islet]- Insulin
(2) Alpha cells- glucagon
(3) Delta cells- somatostatin
(4) PP cells- pancreatic polypeptide
(5) epsilon- ghrelin

88
Q

Insulin + Amylin

A

secreted together which is why lots of insulin secretion can lead to beta cell death. Amylin proteins can build up and cause pancreatic damage.

89
Q

Glucose sensing + insulin release

A

glucose flows into glut-2 channels and is sensed by GLUCOKINASE. This causes G6P relese of ATP and closure of K+ channel (via its SUR subunit). Depolarization causes insulin vesicles to release insulin.

90
Q

Insulin Receptors

A

Receptor Tyrosine Kinase. Ligand binding causes autophosphorylation of beta subunit.

91
Q

Insulin action mechanism

A

Binding to insulin receptor activates insulin receptor substrates (IRSs) which activate cascade leading to insertion of GLUT4 into membrane.

2 main pathways:

(1) PI3K (PKB) is main mediator for GLUT4 insertion
(2) MAPK mediates other growth/mitogenic actions of insulin

92
Q

A cells and L cells

A

Both use preproglucagon

A-cells (pancreas): cleave to form and secrete glucagon
L-cells (intestines): cleave to form and secrete active GLP-1/GLP-2. These GLPs potentiate insulin release from B-cells and are stimulated by carb release in intestines.

93
Q

Ghrelin

A

epsilon cells of pancreas

stimulates food intake and increases GH release. Inhibits insulin function

94
Q

Metabolic switch

A

High flow of proteins from muscle mass breakdown causes ketone bodies to be used as the energy source for brain and decreases the reliance on glucose. This SAVES PROTEIN and MUSCLE MASS.

95
Q

Metabolic syndrome

A

Usually means pre-diabetes

4 criteria

Visceral obesity; insulin resistance; dyslipidemia (too many lipids); hypertension

96
Q

WAT

A

White Adipose Tissue

Leptin –> primary hormone

97
Q

SREBP-1C

A

Transcription factor

promotes TG synthesis; activated by lipids and insulin

98
Q

PPAR-gamma

A

steroid hormone

regulates TG storage and adipocyte differentiation (makes more fat cells)

99
Q

TZD

A

uses PPAR-gamma to make more fat cells thus increasing cells available to take up glucose. Side effect = weight gain.

100
Q

Name the appetite stimulators and inhibitors

A

STIMULATORS: neuropeptide Y; AGRP

INHIBITORS: aMSH; cocaine-amphetamine regulated transcript (CART)

101
Q

Numbers for T2DM diagnosis

A

HbA1C (average plasma glucose [ ]) > 48mMol or 6.5%

Fasting blood glucose > 125mg/dl

Oral glucose tolerance test > 200mg/dl

102
Q

Treatment of T2DM

A

METFORMIN: first line of treatment; increases insulin sensitivity and glucose uptake; inhibits hepatic gluconeogenesis

SULFONYLUREAS: increase insulin secretion

ALPHA-GLUCOSIDASE INHIBITOR: delays intestinal absorption of carbohydrates.

103
Q

Mechanism of ketoacidosis

A

Body thinks it’s starving –> increased lipolysis –> FFA release (hepatic precursor for ketone acids) –> metabolism of ketone bodies –> blood acidity –> ketoacidosis

104
Q

Main reason for altered mental status with uncontrolled diabetes

A

extremely high plasma osmolality

105
Q

Critical genes expressed during islet cell development

A

PDX-1: important for islet neogenesis + beta cell proliferation

TCF72: downstream targets which regulate beta cell proliferation

106
Q

Incretin

A

synthetic which looks to decrease blood glucose levels. Some positive effects on insulin function. GLP is main incretin. Released due to carbs in intestines.

107
Q

EPO

A

Erythropoietin:

Kidney hormone which stimulates RBC increase. If hematocrit raises too quickly, there will be hypertension.

108
Q

ANP/BNP

A

secreted from heart in response to stretch. Potent vasodilators and increase sodium excretion. Higher levels with CHF and renal failure. Lower levels with obesity. Increases with age. Women have twice as much

109
Q

Endocrine disruptor

A

chemicals that interfere with body’s endocrine system and produce adverse effects.

Ex.’s PCB and DES

110
Q

PCB

A

competes with thyroid hormone for binding to transport protein. Circulating thyroid hormone is degraded faster causing compensatory production increase and thus goiter.

111
Q

DES

A

synthetic estrogen once given to pregnant women to reduce birth complications. Led to 40% increase in vaginal/cervical cancer for the daughters.

112
Q

Major steroid hormones

A

CORT, Androgens, Estrogens, Vit D

113
Q

Major Peptides/protein hormones

A

Insulin, PTH, pituitary and hypothalamic releasing hormones

114
Q

Amine Hormone

A

T3/T4, Catecholamines, Indoleamines

115
Q

DHEA from adrenal gland serves as a precursor for what?

A

Testosterone in the testes

116
Q

PeVN

A

Periventricular Nuclei

Secretes Somatostatin (GHRH Inhibitor)

Physiology (12 decks)

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