Lecture 4+5 Flashcards
conversion of cholesterol to pregnenolone?
that is done by the enzyme P450scc or also known as CYP11A
what kinds of hormones are synthesized in the adrenals? examples?
Glucocorticoids: Cortisol
Mineralocorticoids: Aldosterone
Weak Androgens:
Dehydroepi-androsterone (DHEA)
Androstenedione (ADD)
types of hormones produced in the gonads and corpus luteum? examples?
male gonad: androgens (testosterone)
female gonad: estrogens (Estradiol)
corpus luteum: progestins (progesterone)
aldosterone synthesis and regulation?
cholesterol… pregnenolone….. progesterone
11-deoxycorticosterone….. corticosterone is converted to aldosterone by aldosterone synthase or CYP11B2
angiotension II leads to the synthases of that enzyme
where is cortical synthesized?
how is it regulated?
produced in the zona fasciculata
ACTH activates protein kinase A
Protein kinase A activates cholesteryl esterase
StAR moves the cholesterol into the mito (regulated step)
P450scc is regulated by cholesterol availability
androgen synthesis? how many carbons?
what happens when they go into the blood?
Androgens have 19 Carbons and are mainly produced in the zona reticularis
If in adipose tissue DHEA and androstenedione are converted to estrogens by CYP 19 aromatase
If in extra-adrenal tissue they are converted to testosterone by 17 beta hydroxysteroid DH-3
what are the different types of congenital adrenal hyperplasia’s?
- 3 hydroxysteroid DH deficiency
- 17 alpha hydroxylase deficiency
- 21 alpha hydroxylase deficiency
- 11 beta hydroxylase deficiency
3 hydroxysteroid DH deficiency
effects?
what is impacted?
blood pressure - low blood glucose - low androgens - variable (high DHEA) salt excretion in urine ambiguous genitalia in both sexes
less aldosterone and less cortisol due to low progesterone
less androstenedione
CYP 17 or 17 alpha hydroxylase deficiency
effects?
impact?
hypertension
low blood glucose
decreased androgens
female like genitalia in both sexes
Low cortisol, low DHEA, low ADD, low aldosterone
But high aldosterone intermediates
CYP 21 or 21 alpha hydroxylase deficiency
hypotension often low blood glucose increased androgens hyponatremia hyperkalemia
low aldosterone and low cortisol
high DHEA and ADD
male seem normal, but virilization early
female have male-like and virilization later
CYP11B1 or 11 beta hydroxylase deficiency?
mild hypertension
low glucose
increase androgens
low cortisol and low aldosterone
sex hormone synthesis in male gonads?
hypothalamus releases GnRH to anterior pituitary
anterior pituitary releases LH and FSH
LH to leydig cells for testosterone production
FSH to steroli cells for spermatogenesis
Formation of testosterone and dihydrotestosterone?
leydig cells have CYP 17 which converts ADD to testosterone
testosterone is activated into dihydrotestosterone by 5-alpha reductase in prostate and hair follicles
DHT has a higher affinity for the androgen receptor
sex hormone synthesis in female gonads?
hypothalamus releases GnRH
goes to pituitary and releases LH and FSH
LH goes to theca cells to produce testosterone
FSH goes to follicle granulosa cells to produce estradiol (take up testosterone to produce estradiol)
conversion of testosterone into estradiol?
aromatase does that conversion (CYP 19)
cushing syndrome or hypercortisolism
syndrome vs disease
symptoms?
high blood glucose
normal to high blood pressure
increased synthesis of androgens
tumor in Z. fasciculata (Low ACTH) is cushing syndrome
cushing disease = pituitary tumor (high ACTH)
abnormal fat distribution
muscle loss
increased cortisol and adrenal androgens
addison’s disease
destruction of the adrenals
hyperpigmentation, bonze coloration, weight loss, muscle weakness
decreased synthesis of all corticoids
low fasting blood glucose
low blood pressure
low to no androgens
Panhypopituitarism
cause?
types?
children vs adult
due to a deficiency in all pituitary hormones
may be congenital or occur due to infarction
Sheehan’s syndrome due to postpartum hemorrhage
children:
dwarfism, hypogonadism, and mental retardation
adult:
hypothyroidism, low sex hormones, low glucocorticoids
pituitary stalk injury?
can be due to whiplash injury
can result in DI
panhypopituitarism
hyperprolactinemia
function of prolactin?? regulated by?
breast development
milk production
inhibits ovulation by suppressing GnRH
regulated by Dopamine (PIF)
action of dopamine on anterior pituitary
decrease cAMP, decrease Ca
inhibit prolactin release and synthesis
prolactin at target tissues
increase tyrosine kinase
increase gene expression
prolactin effects
excess secretion of prolactin?
medicine?
galactorrhea
decreased libido
decreased ovulation
bromocriptine, dopamine agonist is used
posterior pituitary hormones
oxytocin and ADH
what increases ADH secretion
increased ECF osmolarity
decreased ECF volume
mechanism of ADH in kidney?
ADH binds to V2R
increase cAMP
increase AQP2 production and movement to lumen side of cells
mechanism of ADH in blood vessel
ADH bind to V1R
increase IP3 and DAG
increase Ca
contraction of blood vessels
central DI
low levels of ADH
brain lesions
treated with dDAVP (ADH analogue)
spike in graph after water fast and ADH is given
nephrogenic DI
high levels of ADH
defects in V2 receptor or 2nd messengers
or hypercalcemia or lithium treatment
no change in line after fast and given ADH
SIADH and treatment
ADH secreting tumor
increase ADH secretion (H20 retention)
increased urinary concentration
decreased serum osmolarity
treat with demeclocycline (ADH antagonist) or water restriction
what increased oxytocin release?
mechanism of action?
nursing a baby or pressure against the cervix
bind to receptor, increase IP3 and DAG, increase Ca, and increase SM contraction
