2-6: 5/11: Hypothalamic/pituitary/adrenal Axis

Front 1

Describe the release and regulation of cortisol beginning at the level of the hypothalamus.

Back 1

Hthal: CRH-->Pit: Corticotropin (ACTH)-->Adrenals: Cortisol

Cortisol INHIBITS Pit: ACTH, Hthal: CRH

Front 2

What are the different regions of the adrenal gland and how they differ?

Back 2

Medulla

Cortex (following regions going from OUTSIDE in)
Glomerulosa: Salt (Aldosterone)
Fasciculata: Sugar (Cortisol--LARGEST layer)
Reticularis: Sex (Androstenedione)

Front 3

Salt is regulated by __________.

Back 3

Aldosterone

Front 4

Describe the physiologic events following a fall in blood pressure.

Include all ions effected.

Back 4

BP Falls
Activates JGA in kidney to release renin
Renin: Antiogensinogen-->AgI
Angiotensin Converting Enzyme: AgI-->AgII
AgII-->
Directly stimulates vasoconstriction
Stimulates aldosterone production in adrenal gland

Aldosterone doesn't require a binding protein and is carried in tiny concentrations

Aldosterone acts on kidney to retain salt and water, and to excrete potassium

BP restored

Front 5

High blood pressure inhibits _____.

Back 5

Renin

Front 6

Other than a decrease in blood pressure, what are other activators of aldosterone?

Back 6

Elevated K+
Elevated ACTH (minor)

Front 7

_______ does not require a binding protein and circulates in ______ concentrations.

Back 7

ALDOSTERONE doesn't require a BP and circulates in TINY concentrations

Front 8

What factors contribute to the release of cortisol?

Include all hormones.

Back 8

Circadian rhythms

Stress (illness, fever, untx'd depression, eating disorders)

Hthal: CRH (CRF), vasopressin (increases when need more water!)

CRF increases precursor of ACTH (POMC)-->Cortisol

Vasopressin increases ACTH secretion-->Cortisol

Front 9

What are the non-regulatory effects of cortisol?

Back 9

Metabolism of ROH, Protein, Fat (gluconeogenesis)

Response to stress (increase vascular tone)

Controls inflammation (prednisone, dexamethasone)

Front 10

Cholesterol is a precursor of which three hormones?

What is the initial step of its conversion to one of these hormones? What enzyme is required for this to occur?

Back 10

Aldosterone, Cortisol, Testosterone

Cholesterol-->Pregnenolone via cyp450 (REQUIRES ACTH)
THIS IS RATE LIMITING

Front 11

DHEAS is produced in the _______ and a precursor to ___________ which is converted to __________.

Back 11

DHEAS is in zona reticularis

17-OH-P-->DHEAS-->Androstenedione-->Testosterone

(converted to testosterone in periphery)

Front 12

When does cortisol peak? Nadir?

Back 12

Peak ~6AM
Nadir ~12AM

Front 13

90% of cortisol circulates bound to ___________.

Effect on half-life?

Back 13

Binding proteins:

cortisol binding globulin (75%)
albumin (15%)

Thus, prolonged half life

Front 14

Describe the metabolism of cortisol.
How and why does this differ by organ?

Back 14

Tissue 11beta-hydroxysteroid De-OHase inactivate to cortisone (kidney has HSD-2 isozyme!) and activate cortisone to cortisol (liver, adipose; HSD-1 isozyme!)

Cortisol can bind to aldosterone receptors (aldosterone travels in tiny concentrations), don't want to activate aldosterone receptors while in kidney.

Front 15

Why is licorice linked to hypertension?

Back 15

Deactivates 11beta-hydroxysteroid dehydrogenase in (HSD-2 isozyme) kidney and cortisol binds aldosterone receptors

Front 16

How does cortisol increase serum glucose?

Back 16

-Decreases sensitivity to insulin
-Inhibits amino acid utilization (will break down muscle at high enough concentrations)
-Increases lipolysis, gluconeogenesis

Front 17

What is the effect of cortisol on the circulatory system?

Back 17

Maintains capillary integrity and vascular tone

Activates alpha receptors!

Front 18

What are the effects of cortisol on the sympathetic and central nervous systems?

Back 18

SNS: epi synthesis
CNS: regulates appetite, euphoria, sleep

Front 19

___________ is the major adrenal androgen.

Back 19

DHEAS

Front 20

What is adrenarche?

What hormone regulates it?

Back 20

Adrenarche: dx/dy of sweat glands and terminal hair (pubic, axillary) at puberty

Regulated by testosterone

Front 21

__________ accounts for 5% testosterone in men, and ____ in women.

Back 21

Androstenedione:

5% of testosterone in men (have testicles)

40-60% in women

Front 22

The adrenal medulla synthesizes ___________, which is regulated by _________.

Back 22

Epi, NE

Cortisol regulates NE-->Epi via PNMT (phenylethanolamine-N-methyltransferase)

Front 23

This hormone is derived from a tyrosine precursor.

Back 23

NE, E

Front 24

Practical way of measuring Epi, NE.

Back 24

Metabolites!

If secreting too much Epi: measure metanephrine

If secreting too much NE: measure VMA, normetanephrine

Front 25

____________ is a modified sympathetic ganglion.

Back 25

Adrenal medulla

Front 26

80% of catecholamine production is __________.

Back 26

Epinephrine

Front 27

alpha receptors (1,2) vs beta receptors (1,2,3)

Back 27

Alpha1: CV - increase vasoconstriction
Beta1: CV - increases contractility

Alpha1: Extravascular Smooth Muscle - contraction (GI, uterus, bladder, dilation of pupils)
Beta2: Extravasc SM - relaxation/vasodilation (GI, uterus, bladder, trachea, muscle, vessels)

Metabolic:
a1, b2: increase glycogenolysis
b1: increase O2 consumption, heat
b3: lipolysis

Front 28

What is the effect of insulin on catecholamines?

Back 28

Insulin inhibits catecholamines