Androgens and Glucocorticoids Flashcards
principle adrenal androgen secreted by zona reticularis
dehydroepiandrosterone (DHEA)
DHEA is secreted primarily as
DHEA sulfate (DHEAS)
what serve as indicators of adrenal androgen production
DHEA and DHEAS plasma levels
the zona reticularis secretes small amounts of what alongside DHEA
androstenedione
metabolism of DHEA is what and why
slow
b/c of high affinity for albumin
DHEA and androstenedione (what is their androgen activity like and why)
little androgen activity b/c of low affinity for androgen receptor
what happens to DHEA and androstenedione
converted to more potent androgens peripherally
fetal adrenal cortex is composed of what
outer neocortex
larger inner fetal zone
the outer neocortex of fetal adrenal gland contains what
cells that will differentiate into three morphologically distinct zones of the adult adrenal
the inner fetal zone of the fetal adrenal gland does what
source of DHEA sulfate
what happens to DHEA sulfates produced by fetal adrenal gland
converted to estrogens by placenta
circulating levels of adrenal androgens are relatively constant when
early childhood
circulating levels of adrenal androgens begin to rise when
6-7 years old in girls
7-8 years old in boys
adrenarche (what is it)
age at which circulating levels of adrenal androgens begin to rise
what produces DHEAS in fetus
inner fetal zone (involutes at birth)
growth of axillary and pubic hair the proceeds gonadal steroidogenesis is due to what
biologically active androgens that are derived from adrenal androgens
adrenarche (relation to puberty)
adrenarche does not appear to be involved in the initiation of puberty
adrenal androgens in males after puberty (what about em)
unimportant b/c of large amounts of androgens produced by testes
in females androgens are required for what
maintenance of libido
growth of pubic and axillary hair
what happens to androgen levels throughout adolescence
increase progressively
major source of androgen (for males and for females)
males- testes (after puberty)
females- adrenal gland
what plays a role in regulating adrenal androgen secretion
ACTH
adrenal androgens do or do not exert a negative feedback effect on ACTH
do not
glucocorticoid synthesis occurs where in the adrenal cortex
zona fasciculata
zona reticularis
glucocorticoid synthesis occurs in the adrenal cortex in response to what
ACTH
most important glucocorticoid in humans
cortisol
most accurate estimate of daily cortisol output is
24-hour urinary exertion of unmetabolized cortisol
enhanced activity of synthetic glucocorticoids is due to what
increased affinity for the glucocorticoid receptor
delayed plasma clearance
what is the principle physiological regulator of cortisol release
ACTH
ACTH is the cleavage product of what
POMC
ACTH is released from corticotropes in what type of pattern
secretory pulses throughout the day
on binding its receptor ACTH stimulates formation of what via what
cAMP formation via Gs protein mediated activation of adenylyl cyclase
effects of acute ACTH stimulation are
increase in hydrolysis of stored cholesterol esters
increase in synthesis of StAR protein
increase in steroid hormone synthesis
increase in blood flow to adrenal cortex
effects of chronic ACTH stimulation are
increase in growth and cell proliferation in the zona fasciculate and reticular
increase in synthesis of steroidogenic enzymes, LDL receptors and other proteins
effects of long term suppression of ACTH
adrenal gland atrophy
excessive ATCH production causes
adrenal gland hypertorphy
principle regulator of ACTH secretion is
corticotropin releasing hormone (CRH)
CRH stimulates ACTH synthesis and release by what type of mechanism
cAMP-dependent
AVP promotes ACTH synthesis and release how
potentiating the action of CRH by activating IP3 pathway via Gq
cortisol is released according to what type of pattern
pulsatile (due to pulsatile secretion of ACTH) but in accordance to circadian pattern
cortisol release is characterized by what type of rhythm
diurnal rhythm
cortisol levels are highest when
in the morning upon wakening
cortisol levels are lowest when
in the late evening hours
with time changes in sleeping patters dow hat to cortisol release
change ones diurnal pattern of cortisol release
circadian pattern of cortisol release is regulated by what
suprachiasmatic nucleus of hypothalamus
efferent fibers from the SCN project to where to regulate the diurnal pattern of CRH release
paraventricular nucleus (PVN)
the diurnal pattern of CRH release establishes what
diurnal pattern of ACTH release (and thus cortisol levels)
how does CNS mediate the effects of stress on cortisol release
increasing activity of CRH-secreting hypothalamic neurons
stress mediates the release of what by CRH secreting neurons (other than CRH)
vasopressin
vasopressin does what in relation to cortisol
potentiates CRH-medated ACTH secretion
the effects of stress can override what
diurnal effects and negative feedback control
in absence of ACTH stimulation what happens to cortisol synthesis
declines
cortisol has negative feedback effects on what
CRH and ACTH
cortisol is essential for what
survival
cortisol plays a critical role in?
enabling the body to adapt to fasting and respond to stressful conditions
many actions of cortisol are misunderstood why
it often plays a permissive role in regulating cell function
permissive role of cortisol (what does it mean)
acts by making sure that the cell has the capacity to fully respond when the process is activated
permissive role of cortisol (name one)
induces expression of glycogen synthase
cortisol plays essential role in preventing what during a fast
hypoglycemia
how does cortisol prevent hypoglycemia during a fast
inducing expression of enzymes that support glucose production
what does cortisol do in the liver
promotes gluconeogenesis
how does cortisol promote gluconeogenesis
mobilizes amino acids
how does cortisol mobilize amino acids
inhibiting protein synthesis and stimulating protein catabolism
cortisol has permissive effect on formation of?
glycogen
cortisol conserves blood carbohydrates how?
blocking glucose uptake by skeletal muscle and adipose tissue
what happens to levels of circulating fatty acids and glycerol within a matter of hours of beginning a fast
increase in both
during a fast what happens to circulating levels of cortisol
stay the same
cortisol’s stimulatory effects on catecholamine-induced lipolysis are mostly what?
permissive
when present in excess what does cortisol promote (in terms of fat) and where
fat deposition
especially in trunk and face
hypoadrenal patients tend to exhibit what during a fast?
fasting hypoglycemia
individuals subject to chronic glucocorticoid excess tend to be what?
hyperglycemic and hyperinsulinemic
in glucocorticoid excess what is the result of the catabolic actions of the glucocorticoids
muscle weakness and skin and connective tissue wasting
people with glucocorticoid deficiency or chronic excess show what type of CNS issues
mood behavior wakefulness perception of sensory signal intensity appetite
what effect does cortisol have on calcium
inhibits uptake by gut and reabsorption by kidney
what effect does cortisol have on erythropoiten synthesis
stimulates it
cortisol effects what in development
alveolar maturation and surfactant production
what use do glucocorticoids have in anticipated premature delivery
accelerate fetal lung development
excess levels of glucocorticoids increase risk of what bone problem
osteoporosis
glucocorticoids act directly on the bone to
inhibit bone formation
lesser extent promote bone resorption
glucocorticoids have what effect on inflammatory response
suppress it
glucocorticoids suppress the inflammatory response how
blocking expression of genes that code for pro inflammatory cytokines
glucocorticoids inhibit synthesis of key enzymes like what? that catalyze the synthesis of inflammatory agents
phospholipase A2
glucocorticoids do what to NO synthase
inhibit it
cortisol induces synthesis of what anti-inflammatory protein that inhibits phospholipase A2
lipocortin (annexin)
