Fertility Hormones of the Hypothalamo-Pituitary-Ovarian Axis Flashcards
the 3 feedback loops of the HPO axis are
long, short and ultrashort
describe the long feedback loop
effects of ovarian hormones (estrogens, progesterone, inhibin) on both the hypoth (GnRH) and pituitary (FSH, LH)
when is the long feedback loop inhibitory
in the follicular phase
when is the long feedback loop stimulatory
in the preovulatory phase
the 3 ovarian hormones involved in the long feedback loop are
estrogen, progesterone and inhibin
describe the short feedback loop
effects of pituitary hormones (FSH, LH) on the GnRH
T/F: the short feed back is usually stimulatory
F. usually inhibitory
describe the ultrashort feedback loop
Autoregulatory effect of GnRH on its own synthesis
T/F: the ultrashort feedback loop is usually inhibitory
T
T/F: in the follicular phase the developing follicles produce only estrogen
F. also small qt of progesterone
the preovulatory peak of estrogen in the follicular phase is sustained for how many hours
24 - 48 hrs
when is estrogen inhibitory in the follicular phase
The slow and steady rise is inhibitory to GnRH, FSH and LH
when is estrogen stimulatory in the follicular phase and to what
The peak state is stimulatory (causes a surge of LH - this surge is responsible for ovulation)
if pregnancy occurs, the corpus luteum produces progesterone for how long
10-14 weeks
GnRH = Gonadotropin Releasing Hormone is also known as
LHRH = Leuteinizing Hormone Releasing Hormone
T/F: GnRH is a nonapeptide
F. decapeptide
GnRH is secreted where
arcuate nucleus of the hypothalamus in a pulsatile manner
describe the GnRH pulses in the follicular and luteal phases of the ovarian cycle
a. 1 hourly in small amounts in the follicular phase
b. 2-3 hourly in larger amounts in the luteal phase
GnRH is modulated by these 4 mechanisms
ultrashort, short, long loop feedback and neurotransmitters/neuromodulators
Ultrashort feedback loop for GnRH
- High GnRH concentraion = Inhibits further GnRH secretion from the hypoth / decreases GnRH receptors in the pituitary
- Low GnRH concentration = Stimulates GnRH secrretion from the hypoth / increases GnRH receptors in the pituitary
Short feedback loop for GnRH
FSH and LH inhibits GnRH production and secretion
T/F: sustained peak levels of estrogen in the preovulatory phase stimulates GnRH secretion
T
Long feedback loop for GnRH
Estrogen and progesterone inhibit GnRH secretion except in the pre-ovulatory phase when sustained peak levels of estrogen stimulates GnRH secretion with consequent LH surge and ovlation
the 2 catecholamines that inhibit GnRH secretion are
Dopamine and serotonine
the catecholamine that stimulates GnRH secretion
Norepinephrine
the 3 endogenous opioids involved in the regulation of GnRH
endorphins, encephalins, dymorphins
endorphins are increased with exercise and stress. T/F
T
T/F: the endorphins inhibit GnRH secretion
T
T/F: the endorphins stimulate dopamine secretion
F. inhibit dopamine secretion leading to hyperprolactinaemia due to withdrawal of dopamine inhibition on the lactotrophs
how do the endorphins cause infertility
They inhibit GnRH and dopamine secretion
Can lead to hypothalamic amenorrhoea and hyperprolactinaemia with subsequent infertility
the 3 peptides involved in GnRH regulation are
Inhibin, follistatin, activin
where are the peptides involved in GnRH regulation produced
They are produced by both pituitary cells and granulosa cells of the ovary under the influence of GnRH
effect of activin on GnRH secretion
stimulates
effect of follistatin on GnRH secretion
inhibits GnRH secretion
effect of inhibin on GnRH secretion
blocks GnRH receptors on the pituitary
the 3 cell types of the anterior pituitary
chromophobes, acidophils and basophils
T/F: the chromophobes secrete prolactin
F. do not secrete any hormone and are called resting cells
the 2 hormones produced by acidophiles are
prolactin and growth hormone
the hormones produced by the basophils are
FSH, LH, ACTH and TSH
which of the cell types are the resting cells
chromophobes
where is oxytocin produced
the paraventricular nucleus of the hypothalamus but transported via neurons to the posterior pituitary from where it is secreted
T/F: the gonadotropins are peptides
F: water soluble glycoproteins with high molecular weights
The alpha sub units of these 4 hormones are similar in chemistry
FSH, LH, TSH and hCG
FSH levels peak at the — day of the menstrual cycle (pre-ovulatory phase) and gradually declines to its basal level around the — day
12th and 18th
T/F: the gonadotropins have nuclear receptors
F. Their receptors occur on the cell membane surface
T/F: the gonadotropins are secreted in pulses in response to GnRH pulses
T
FSH stimulates granulosa cells to produce –, –, and –
inhibin A, inhibin B and activin
T/F: FSH stimulates plasmin activator necessary for ovulation
T
T/F: the LH surge triggers ovulaion, which occurs about 12 hours after LH peak
T
T/F: Rising levels of estradiol, progesterone and inhibin inhibits GnRH, FSH and LH secretion
T
T/F: Sustained elevated levels of estradiol stimulates GnRH and thus LH secretion (LH surge)
T
T/F: prolactin is a polypeptide hormone
T
T/F: Elevated prolactin levels inhibits GnRH pulses (resulting in anovulatory infertility)
T
T/F: Prolactin secretion is stimulated by dopamine
F. inhibited
the nonapeptide hormone of the pituitary
oxytocin
‘two cell two gonadotropin theory’
The theory states that LH stimulaes the theca cells to produce androgens (which move into the granulosa cells) while FSH stimulates the granulosa cells to convert androgens to estrogens (by aromatization)
least potent estrogen
estriol
T/F: estrone is 10 times more potent than estriol
T
describe the potency of estradiol in relation to the other estrogens
10 times more potent than estrone, 100 times more potent than estriol
percentage of free and biologically active estrogen
1%
percentage of estrogen bound to albumin
30%
percentage of estrogen bound to SHBG
69%
Estradiol (E2) and estrone (E1) are inactivated by conversion to —
estriol which is then conjugated in the liver and excreted in bile and urine
T/F: cervical mucus under estrogen effect is alkaline with less protein
T
T/F: Progesterone only has effect on an estrogen primed endometrium
T
T/F: estrogen increases blood coagulability
T. Increases blood coagulability (↑Platelet adhesion; ↑fibrinogen)
effect of estrogen on sodium and nitrogen
increases retention
effect of estrogen on cholesterol
Lowers blood cholesterol
T/F: estrogen raises blood levels of binding globulin, protein bound iodine and cortisol
T
describe the positive feedback of estrogen LH
Elevated (>200pg/mL) and sustained (24-48 hours) levels of estradiol stimulates LH release (mid cycle surge) by ↑ GnRH secretion and its receptor sensitivity in the pituitary
level of estrogen required for the positive feedback on LH
> 200pg/mL sustained (24-48 hours)
T/F: Progesterone inhibits the positive feedback of estrogen on LH in the post ovulatory phase
T
T/F: before ovulation, trace amounts are secreted from un-luteinized theca and granulosa cells of the developing ovarian follicle and stroma
T
progesterone is metabolised in the liver and excreted in urine as
pregnanediol
serum level of progesterone in the follicular phase
< 1ng/mL
serum level of progesterone in the midluteal phase
5-25ng/mL
percentage of progesterone bound to albumin
79%
percentage of free serum progesterone
3.3%
percentage of progesterone bound to steroid hormone binding globulin
17.7%
T/F: progesterone acts on all estrogen primed tissues of the genital tract and the breast
T
progesterone raises the basal body temperature by –
0.2-0.5°C
T/F: progesterone promotes sebum secretion by skin glands
T
T/F: progesterone causes fluid retention
T
T/F: progesterone reduces tubal motility
T. Reduces tubal motility (may predispose to ectopic pregnancy)
T/F: androgens are produced only be the theca cells of the ovary
F. Produced by all cells of the ovary (stromal, theca and granulosa cells) from cholesterol
3 principal ovarian androgens are
dehydroepiandrosterone, androstenedione and testosterone
describe the metabolism and excretion of ovarian androgens
Metabolized in the liver to 11-deoxy-7-ketosteroids (androsterone and etiocholanone) that are excreted in the urine
the 2 androgen metabolites excreted in the urine are
androsterone and etiocholanone
T/F: Inhibin - inhibits FSH secretion
T
T/F: Activin - stimulates FSH secretion
T
T/F: Follistatin - inhibits FSH by inhibiting activin
T
AMH is produced by
granulosa cells of primordial (< 6mm) follicles
T/F: AMH is a peptide hormone
T
T/F: AMH levels reflect the number of developing follicles in the ovary
T
T/F; AMH helps follicular development and oocyte maturation
T
T/F: AMH used for testing ovarian reserve
T
