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kris Endocrinology > Final revision > Flashcards

Final revision Flashcards

1
Q

Describe the hypothalamus-pituitary- adrenal axis

A
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2
Q

What are the enzymes that are specific for each adrenal gland zone that allow them to produce their specific hormones

A

Z. fasciculata: none

Z. glomerulosa: aldosetrone synthase

Z. retucularis: 17, 20 lyase (DHEA-> androstenedione)

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3
Q

What is the first step common to all steroids?

Where does it take place?

How is it formed

A

The first step common to all steroids is the formation of pregnenolone from cholesterol

Takes place in the mitochondria

On inner mitochondrial membrane, P450scc (side-chain cleavase) cleaves the side chain of cholesterol to produce pregnenolone

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4
Q

How is cholesterol taken up into the mitochondria for steroidogenesis?

A

v Uptake of cholesterol is a rate limiting step and

v Regulated by StAR protein (Steroid Acute Regulatory protein)

(smooth endoplasmic reticulum)

v StAR is cAMP-inducible gene and increases in response to tropic hormones (i.e. ACTH in the adrenal gland and gonadotropins in gonads)

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5
Q

Cortisol can also activate __ receptor

A

Cortisol can also activate aldosterone receptor

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6
Q

How is cortisol, hypokalemia and hypertension connected?

A

kidney and other cell types inactivate cortisol to prevent inappropriate activation of the aldosterone receptor – when cortisol levels are too high HSD2 is overwhelmed and cortisol stimulates Na+/K+ exchange in kidney causing hypokalemia and hypertensiom

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7
Q

Metabolic effects of cortisol

A

Effects are generally opposite to insulin and similar to GH (i.e. increase in blood glucose) at the expense of protein and fat. Action depends on the target cells:

  • Muscle cells, adipocytes lymphocytes: increased Catabolism
  • Liver: increased Glycogen synthesis and Gluconeogenesis
  • Increase of blood glucose despite the increase in glycogen storage
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8
Q

Anti-inflammatory effects of cortisol

A
  • Cortisol inhibits the immune response and hence is anti- inflammatory
  • Widely used to treat inflammatory conditions (i.e. rheumatoid arthritis and other immune disorders)
  • Leads to atrophy of the lymph nodes and thymus (activation of apoptosis)
  • Decrease in number of lymphocytes and antibody production vPatients become susceptible to infections
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9
Q

Cortisol and norepinephrine

A
  • Sensitizes arterioles to the action of norepinephrine (hypertension)
  • Permissive effect on the action of norepinephrine on carbohydrate metabolism (glycogenolysis → hyperglycemia)
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10
Q

cortisol is primarily regulated by _ hormone _

A

cortisol is primarily regulated by trophic hormone ACTH

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11
Q

Transport of circulating cortisol

A
  • Corticosteroid Binding Globulin (CBG = Transcortin)
  • Synthesized by the liver & has high affinity for cortisol
  • Binds about 75 % of all cortisol in the plasma,about 10 % is “free” and 15% is bound to serum albumin
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12
Q

What is cushings syndrome

A

Increased glucocorticoid activity (cortisol excess)

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13
Q

What is addison disease?

Causes?

A

Adrenal hypofunction (cortisol deficiency)

Most commonly due to destruction of the adrenal gland by an autoimmune response

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14
Q

Name adrenal steroid hormones groups and functions

A

• Mineralocorticoids

– Affect mineral homeostasis

• Glucocorticoids

– Affect glucose metabolism and immune function

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15
Q

Name eicosanoid hormones common precursor

A

arachidonic acid

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16
Q

Name adrenal medulla amino acid hormones and their common function

A
  • Epinephrine
  • Norepinephrine
  • Dopamine
  • Often used as neurotransmitters
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17
Q

Are endocrine glands permanent or transient structures?

A

Both

– Pituitary, adrenal, pancreas are permanent

– Ovarian follicle and corpus luteum are transient

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18
Q

Name neurons that produce hormones

A

– Hypothalamus
– Posterior pituitary

– Adrenal medulla

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19
Q

Between which AA are disulphide bridges formed

A

Between cysteines

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20
Q

Hormones are stored in vessicles are preprohormone/ prohormone/ hormone

A

prohormone

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21
Q

Bronzing and excessive freckles are associated wiht which disease?

A

Addison disease

Lack of hormones increases ACTH secretion by the pituitary (removes –ve feedback)

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22
Q

Cortisl secretion rhytms

A

Cortisol secretion: maximalbetween 4-8 a.m.

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23
Q

GH and PRL secretion rhytm

A

GH, PRL maximal secretion 1h after going to sleep

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24
Q

Gonadotropin secretion rhythm

A

Released mainly at night during puberty. Released in a pulsatile fashion in adults.

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25
Q

Describe ectodomain

A

Signal binds to ectodomain (NH2 end)

Rich in cysteine residues (S-S bonds for folding).

Often glycosylated.

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26
Q

What are the 3 amino acids that get phosphorylated in the signalling cascade? What is the relative frequency and time of occurence of each?

A
  • Serine, threonine, tyrosine
  • Phosphorylated serines and threonines more abundant than phosphorylated tyrosines
  • Tyrosines phosphorylation often occurs at the beginning of a cascade (many receptors have or induce tyrosine kinase activity)
  • The phosphorylated tyrosines serve as docking sites for down stream signal proteins
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27
Q

What are the 2 types of Tyrosine kinase linked receptor?

A

Intrinsic TK activity

Rectuited TK activity

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28
Q

G⍺ subunits types and functions

A
  • Gs⍺ alpha: Activates adenylate cyclase
  • Gi⍺ alpha: Inhibits adenylate cyclase
  • Gq⍺ alpha: Activates phospholipase C
  • IP3 and DAG and Ca signaling
  • Go⍺ alpha: Activates ion channels
  • G12/13⍺: regulate Actin cytoskeleton
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29
Q

Many receptors of non-endocrine signals also act via_

A

Many receptors of non-endocrine signals also act via G-proteins

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30
Q

intrinsic TK receptor example is _

A

intrinsic TK receptor example is insulin receptor

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31
Q

Structure of a receptor with intrinsic TK activity

A

Hetero-tetrameric structure (2 α and 2 β chains)

Homology with the IGF-I receptor

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32
Q

Sequence of events after insulin binding

A
  1. Autophosphorylation of intracellular domain of receptor
  2. Docking and phosphorylation of IRS-1 and IRS-2 (insulin receptor substrate)
  3. Activation of two major signal pathways- MAPK or PI3 pathway
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33
Q

What are receptors with recruited tyrosine kinase activity characterized by?

A

Characterized by 4 alpha-helices and homology of the ectodomain (hormone binding site)

34
Q

Name receptors with recruited tyrosine kinase activity

A

Best known are the receptors for growth hormone (GH), prolactin (PRL) and leptin

35
Q

GH signaling pathways

A

GH has two binding sites and binds sequentially to two receptor molecules

Dimerization of the cytoplasmic regions initiates signal transduction

First step is to recruit JAK-2: phosphorylates itself, the receptor and other proteins

  • Branch 1: Activation of the transcription regulatory proteins, STAT (4 isoforms)v
  • Branch 2: Activation of the MAPK pathway (as insulin, but JAK2 plays the role of IRS1)
  • Branch 3: Activation of PI3K pathway
36
Q

Jak-stat pathway

A
  1. after jak is rectuited and dimerization occurs
  2. tyrosine kinase activyt is stimulated
  3. they phosphorylate themselves and phosphorylate the receptors
  4. this phosphorylation of the receptor’s cytoplasmic domain allows for recruitment of STAT (has multiple isoforms (1-5))
  5. stat is brough to the receptor
  6. JAK-2 phsophoryalyaes STAT
  7. phosphoryated STAT dimerize and are released from the receptor and go into the nucleus
  8. binds to DNA and change gene expression
37
Q

Classes of NR ligands

A

ligands can be classified in groups:

1) classical
2) vitamins and their derivatives - Vit A and Vit D- these vitamins are lipid soluble, so these derivatives will also be lipid soluble and will bind to nuclear receptor
3) metabolic intermediates and products

38
Q

Steroid vs nuclear receptors

A

steroids function as homodimer

Nuclear receptos function as heterodimer

39
Q

two different ectodermal components of Hypothalamo-hypophyseal tract

A
  1. Rathke’s pouch: outgrowth of the buccal cavity detaches itself and becomes the anterior pituitary
  2. The infundibulum develops from an outgrowth of the neuroectoderm from the floor of the third ventricle. It gives rise to the pituitary stalk, the median eminence and the posterior pituitary.
40
Q

Describe blood supply of anterior pituitary

A
  • anterior pituitary is highly vascularized: capillary bed in anterior pituitary is connected to capillary bed in median eminence through portal veins
  • Releasing factors are secreted into median eminence that go to pituitary
  • Retrograde flow of blood allows for –ve feedback from pit. to hypothalamus
41
Q

What is the name of the vein that carries hypophysiotropic hormones to anterior pituitary

A

portal

42
Q

What is posterior pituitary made of

A

Posterior pituitary is composed of the nerve ending (axons) of neurons whose cell bodies are located in the hypothalamus

43
Q

Oxytocin and vasopressin are produced in the_, packaged into __ which migrate to the __

A

(oxytocin and vasopressin) are produced in the cell bodies, packaged into granules which migrate to the ends of the axons located in the posterior pituitary

44
Q

Hormones of anterior pituitary

A
45
Q

Which receptro type is used by ?

A

Post-receptor intracellular signaling by G-proteins

  • Trophic hormones: Gs⍺ and Gq⍺ proteins. Leads to increased Ca2+ levels and exocytosis of hormone granules.
  • Inhibitory hormones: Somatostatin and dopamine act via Gi⍺ and other mechanisms.
46
Q

What acts as a cricadian pacemaker

A

The suprachiasmatic nucleus or nuclei (SCN)

47
Q

Functions of pineal gland

A
  • Secretes melatonin (hormone of the dark)
  • Induction of sleep
  • Depression of reproductive activity, inhibition of ovulation and semen production in some animals –questionable role in humans
  • Seasonal fluctuations may affect the timing of breeding, migration and hibernation in mammals
48
Q

where are melatonin receptors foudn in the body?

A

Melatonin-receptors are found (almost) everywhere in the human body

49
Q

Which hormones of pituitary are co-expressed/ uniqely expressed

A
  • No unique TSH cells
  • 60-70% GH+ cells express only GH
  • 6-16% PRL+ cells express only PRL (sexual dimorphism-more uniquely prolactin producing cells in females, than in males )
  • Both gonadotropins are co-expressed
50
Q

What is the Largest portion of endocrine cells in anterior pituitary

A

somatotrophs

51
Q

What hormones are stored in somatotrophs?

A

GH

52
Q

Differences in genders in response to GHRH treatment

A

response is stronger in males than females

53
Q

Somatostatin inhibits GH __ but not __

A

Somatostatin inhibits GH secretion but not synthesis

54
Q

How do GH secretioj patterns change thorughout life

A

Levels fetus > child < adolescent > adult

Changes in amplitude but not frequency of pulses

55
Q

Growth hormone signaling

A

Uses rectuited TK

JAK2 -> STAT; MAPK; PI3K

56
Q

effect of suppressor of cytokine signaling (SOCS) on GHR signaling

A

suppressor of cytokine signaling (SOCS) inhibits GHR signaling

57
Q

Growth hormone effects on growth

A

Direct actions: Promotion of cell differentiation

Indirect actions: Induction of IGF-I that promotes cell division and has insulin-like effects

58
Q

Growth-promoting effects of GH via IGF-I

A

Important during childhood growth, but less during gestation and for the neonate.

IGF-I levels parallel growth rate in children

GH and IGF-I promote growth of long bones at the epiphyseal plates (proliferation of cartilage cells, i.e. chondrocytes).

Epiphyses fuse at the end of puberty and longitudinal growth ceases

59
Q

Metabolic effects of GH

A
  • In adults: optimizes body composition, physical function and substrate metabolism
  • Interacts with insulin to regulate Glu, fat and protein metabolism
  • Enhances lipolysis and FA oxidation – imp during fasting
  • Reduces urea synthesis and excretion – Protein sparing
  • Increases AA uptake and protein synthesis
  • Inhibits insulin stimulated glucose uptake
  • Also, GH treatment induces insulin secretion and glucose uptake
60
Q

Regulation of GH release

A
  • Balance between GHRH and somatostatin (GH release inhibiting hormone)
  • Feedback control by IGF-I on pituitary and hypothalamus
  • Feedback control by GH
  • Metabolites:
    • Increase: Hypoglycemia (e.g. produced by insulin administration) Amino acids (arginine)
    • Decrease: Hyperglycemia (oral glucose), free fatty acids
61
Q

Prolactin has stimilair structure to __

A

GH

62
Q

__ and __ are essential for initiation and maintenance of milk secretion

A

PRL and cortisol are essential for initiation and maintenance of milk secretion

63
Q

What regulates PRL gene expression

A

Positive: PrRP, EGF, FGF, VIP, estrogen, TRH, thyroid hormone

Negative: dopamine, endothelin, TGFb

64
Q

What is required for duct system development?

Alveolar growth?

A

Duct: estrogen, GH, adrenal steroids

Alveolar growth: estrogen, progesterone, adrenal steroids

65
Q

ACTH is derived by proteolytic cleavage of _

A

ACTH is derived by proteolytic cleavage of a large precursor molecule pro-opiomelanocortin (POMC)

66
Q

Adrenocorticotrophin (ACTH) and related peptides

A

v Melanocyte stimulating hormones (MSH) -> Darkening of the skin
v Beta-endorphin - Morphine-like activity

v ACTH - Adrenal steroidogenesis

67
Q

Mechanism of action of ACTH

A

v Binds to receptors in the adrenal gland
vActivate Gsα-protein
vEnhanced mobilization of cholesterol.
vIncreased conversion of cholesterol to pregnenolone

68
Q

Control of ACTH secretion

A

vControlled by the hypothalamic hormone CRH

v CRH induced by stress (pain, fear, fever, hypoglycemia)

vLowest around midnight, morning peak and then declines

vCRH action is potentiated by other hormones (vasopressin)

vSubject to feedback control by cortisol

69
Q

Thyrotropin (TSH) structure and recptor type used

A

Two protein chains (⍺ and β) Glycosylated.

Unique β-chain; Common ⍺-chain with FSH/LH

Receptor signaling via G-proteins (cAMP).

70
Q

Tumors secreting _, _ or _ are most common.

A

vTumors secreting PRL, GH or ACTH are most common

71
Q

Factors that stimulate vasopressin release

A

Angiotensin II

Hyperosmolarity

Decreased atrial receptor firing

Sympathetic stimulation

72
Q

WHAT Can lead to diabetes insipidus of pregnancy if over-expressed

A

Vasopressin

73
Q

Natriuretic peptides

what are they, where are they produced, where are thir receptros found

what is the effect

A

v Peptides that increase the excretion of H2O and Na+

v Produced in the heart muscle cells and stored in granules

v Receptors are present in the glomeruli, medullary collecting ducts of the kidney, the zona glomerulosa of the adrenal cortex and in peripheral arterioles

v Increases glomerular filtration

v Reduces blood volume and pressure

74
Q

Where are sex streoids produced and which factors controll this process

A

v Sex steroids are mainly synthesized in the gonads (Females: estrogens and progestogens; Males: androgens) –regulated by gonadotrophins

v Adrenal cortex (mainly zona reticularis) contributes to the production of DHEAS and androstenedione – regulated by ACTH and hypothalamic CRH.

75
Q

Congenital adrenal hyperplasia (CAH)

A

vExcessive androgen production

vMasculinization of genitalia

76
Q

Adrenal medulla and _ cells are part of the _ nervous system

A

Adrenal medulla and chromaffin cells are part of the sympathetic nervous system

77
Q

What is the stimuli of adrenal medulla to release hormones?

A

Preganglionic neurons release acetylcholine to stimulate medulla cells to release hormones

78
Q

Hormones of the Adrenal Medulla

A

Catecholamines (norepinephrine (20%) and epinephrine (80%)) synthesized from tyrosine

79
Q

Other hormones secretion of adrenal medulla

A

Granules also contain met-enkephalin and and leu-enkephalin (related to endorphins).

They are co-excreted with the catecholamines

Enkephalins may block neurotransmitters (like morphine)

act as an endogenous analgesics (runners overcoming pain and being euphoric)

80
Q

effects of epineprhin

A
  • rapidly mobilizes fatty acids as the primary fuel for muscle action
  • increases muscle glycogenolysis
  • mobilizes glucose for the brain by ­increased hepatic glycogenolysis and gluconeogenesis
  • preserves glucose for CNS by decreased insulin release leading to reduced glucose uptake by muscle/ adipose
  • Increases cardiac output

kris Endocrinology (17 decks)

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