Most of estrogen and progestin are made from _____
Ovaries
What are different forms of estrogen and where are they made from?
Beta estradiol (from ovaries)
Estrone (peripheral tissues)
Estriol (liver)
Which hormone influence cholesterol conversion to pregnenolone?
LH in theca cells
Which hormone play a role in stimulating aromatase to convert testosterone to estradiol?
FSH in granulosa cells
What is the enzyme that converts pregnenolone to progesterone?
3beta-hydrodxysteroid dehydrogenase
The first enzyme in cholesterol conversion to estradiol is ______. This process occurs in _____ cells
Cholesterol desmolase
Theca
17 alpha hydroxylase is involved in converting ______ to ______. 17,20 lyase converts ______ to _____.
Pregnenolone to 17-hydroxypregenolone
17 hydroxypregenonlone to DHEA
Conversion of androstenedione to testosterone occurs in _____ cells, and involves ______ enzyme
Granulosa
17 beta hydroxysteroid dehydrogenase
T/F: Adrenal gland produces estradiol
True; but only a limited amount, majority is produced in the ovaries
T/F: progesterone can be converted to aldosterone
True; couple steps involved, but immediately from progesterone via 21 hydroxylase you make deoxycorticosterone and then the 18 hydroxylase and oxidase will take you there
Majority of estrogen and progesterone is bound to _____ in circulation
Albumin (60%)- estradiol
Protein- progesterone (although albumin is a protein, so albumin is most probably true too)
Liver conjugates estrogens to _____ and ______.
Glucuronides and sulfates
T/F: liver also converts estradiol and estrone to the weaker estriol
True
T/F: Liver can convert progesterone to other steroids within minutes of secretion
False; it degrades progesterone to other steroids, major end product is pregnanediol
Major end product of liver progesterone degradation is ______ , and this can be found in urine, which is used to estimate rate of progesterone ______
Pregnanediol
Formation
LH receptors are found in _______ cell(s), FSH receptors are found in _______ Cell(s)
LH found in both theca and granulosa
FSH found only in granulosa
Which cell has both LH and FSH receptors?
Granulosa has both
What is the 2 cell model?
Need both theca and granulosa cells to produce estrogen
Progesterone in granulosa cell goes into theca, which gets converted to androgen in there, and androgen is sent back to granulosa cell which ultimately gets converted to estrogen via aromatase
T/F: the 2 cell model for estrogen production exists because only granulosa cell has FSH receptor, and that is needed for aromatase to convert androgen to estrogen
Why can’t granulosa cell alone make estrogen, why does it involve theca cell?
Granulosa cell cannot turn progesterone to androstenedione (precursor to androgen) because it lacks 17 alpha hydroxylase and 17,20 lyase in the cell, so must involve theca cells which contain those enzymes
In mid menstrual cycle/ late follicular phase, estradiol exert a(n) _______ feedback to hypothalamus and anterior pituitary, which prompts _______ release of GnRH/FSH,LH respectively. This is known as ______
Positive
Increased
LH surge
Between FSH and LH, which is stored more in the anterior pituitary?
LH is stored more, whereas FSH is produced for a “just in time” purpose so not usually stored
Factors that inhibit GnRH transcriptional signaling in gonadotrope?
Luteal phase: estrogen and progesterone
Inhibin from the ovary
Factors that activate GnRH transcriptional signaling in gonadotrope?
Follicular phase: estrogen
Activin from ovary
GnRH secretion frequency is increased by ______ and _____ neurons; GnRH secretion is decreased by _____ neuron
Kisspeptin and glutamate neurons
GABA inhibits it by inhbiting kisspeptin neurons
At puberty, there is ____ activity of kisspeptin neurons and ____ in GABA.
Increased
Decreased (the decreased GABA also disinhibit kisspeptin)
In puberty, GnRH receptor and LH receptor sensitivity _____ and there is also _____ surge in LH
Increase
Nocturnal surge
Changes of hypothalamic neurons could be triggered by :
Increase in adipose tissue
Bone maturation
Leptin stimulation of GnRH
T/F: Gonadotrophs are present before GnRH is in fetus.
True; gonadotrophs present in week 10 of gestation and GnRH 14-16 weeks of gestation
At week ______ gestation, the hypothalamic-pituitary system is functional and GnRH is released
23
Continuous GnRH leads to _____ of gonadotropin release, vs pulsatile GnRH it would ______ gonadotropin release
Downregulate with continuous
Upregulate with pulsatile
Why is there downregulation of gonadotropes with continued release of GnRH?
GnRH receptor, when bound, leaves the membrane and enter the cell, so if GnRH is high constantly, the receptor cannot be replenished fast enough and the response of the gonadotrope decreases
What could be the therapy for diseases that leads to high levels of estrogen?
Continuous administration of GnRH analogs, because this would downregulate gonadotrope release
There is a large increase in gonadotropin at ______, as shown in the spike in graph of total urinary gonadotropin
Menopause, due to ovaries burnout
At both low an high levels, ____ have inhibitory effect on hypothalamus and anterior pituitary. Whereas, at only high level of _____ would this have an inhibitory effect on the HPA.
Estrogen -both high and low
Progesterone – only high (low level of progesterone has stimulatory effect)
When does estrogen exert a positive feedback to HPA?
When the level increases past a threshold and stays above it from two days, estrogen starts to have a positive effect on the HPA. This is usually seen during late follicular phase – LH surge
How is inhibin stimulated?
FSH and estradiol stimulates granulosa cell to produce, and LH receptor on granulosa cell before ovulation can also stimulate
Inhibit is produced by _____
FSH and estradiol stimulating the granulosa cells
T/F: inhibins decrease FSH and LH secretion by the gonadotrophs in the anterior pituitary
False; they only decrease FSH as they have no effect on LH secretion
T/F: Activins are released from the granulosa cells, therefore they increase FSH secretion from the anterior pituitary
True; much like inhibin, activin only affect FSH, no LH activity
Progesterone receptors are special, what are the two things that it can do?
Stimulate glandular secretion and membrane hyperpolarization
Signaling cascade can also inhibit intracellular calcium
T/F: progesterone is mildly thermogenic (increases body temp in luteal phase)
True
Which hormone is responsible for female reproductive tract maturation?
Estrogen
Increase sizes and development of glandular tissues
What is the change in cell type of the vagina during puberty?
cuboidal to stratified
What is the effect of estrogen on skeleton?
Inhibits osteoclasts so they stimulate bone growth
Closes growth plates to end linear growth in puberty
T/F: estrogen increases fat deposition in subcutaneous tissues, like the butt and thighs
True
T/F: estrogen can act like aldosterone and cause sodium and water retention
True; though usually insignificant but can be factor during pregnancy with estrogen levels super high
T/F: estrogen stimulates breast development for milk production and make the breasts swell
False; progesterone does that; estrogens effect on breast is that it stimulates outward appearance and increases stromal tissue and duct and fat on it
Default human is _____ (sex)
Female – without SRY gene. SRY gene leads to testes development
Mullerian is to ____, and wolffian is to ____ (Sex)
Female/ uterus/ fallopian tubes
Male / epididymis/ vas deferens/ seminal vesicles
Starvation would ____ leptin, which ____ Kisspeptin, and would therefore _____ GnRH
Decrease
Decrease
Inhibit
Increase in TRH would ____ prolactin, which ____ kisspeptin and therefore_____ GnRH
