Female Sex Hormones Flashcards
What are the principal steroid hormones secreted by the adult ovary?
Estradiol
Progesterone
Androstenedione
What is the primary source of estrogens in the non-pregnant adult?
Maturing follicle
What is estradiol (E2)?
Principal ovarian estrogen
Most potent
What is estrone (E1)?
Formed from estradiol and androstenedione by peripheral conversion
Fat is a major source of aromatase activity
What is estriol (E3)?
Weak estrogen
Levels are only usually measured during pregnancy
Placenta synthesized large amounts of E3 during pregnancy
What two cells in the follicle are responsible for estrogen synthesis?
Thecal cells
Granulosa cells
What are thecal cells?
Close proximity to blood vessels, source of LDL
Have enzymes to synthesize androgens
Do not produce aromatase, so can’t convert androgens to estrogens
Androstenedione production
What are granulosa cells?
Unable to synthesize androgens
Have high aromatase activity, so they can convert androgens from thecal cells to estrogens
Also expresses 17B-HSD, which converts estrone to estradiol
Describe the hormonal control of thecal and interstitial cells of the ovary.
Possess LH receptors
LH induces androgen biosynthesis via cAMP pathway
Describe the hormonal control of granulosa cells?
Expression of aromatase induced by FSH via cAMP pathway
What are progestins?
Steroids that promote gestation
Progesterone is the most potent
Principal sourc is the corpus luteum
What is the principal circulating androgen in women?
Testosterone
What are the three phases of the reproductive cycle?
Follicular phase
Ovulatory phase
Luteal phase
What is the follicular phase?
Begins with the onset of menstrual bleeding
Preovulatory follicle develops within the ovary
Estradiol primary hormone
Corresponds to menstrual and proliferative phases of the endometrial cycle
What is the ovulatory phase?
Lasts approximately 36 hours and culminates in ovulation
What is the Luteal phase?
13-14 days
Corpus luteum and ovary secretes both progetsone and estradiol
Corresponds to the secretory phase of the endometrial cycle
What is the primordial follicle?
Primary ooctye surrounded by a single layer of poorly differentiated pregranulosa cells
Describe recruitment of primordial follicles
Begins in fetal life and continues in wave-like fashion until the supply is depleted at menopause
What occurs to follicular growth prior to puberty?
Follicular growth occurs but the process is arrested in an early stage
Follicle undergoes atresia
What is a primary follicle?
Primordial follicle leaves the pool of inactive follicles
Zona pellucida forms around the oocyte
Oocyte and granulosa cells increase in size
What extracellular proteins are secreted by the oocyte during the formation of a mature preantral follicle?
ZP1, ZP2, ZP3
Provide species-specific binding sites for sperm cells
How do the granulosa cells mature during mature preantral follicle formation?
Oocyte releases paracrine factor that stimulate the growth and differentiation of the granulosa cells
Granulosa cells begin to express FSH and estrogen receptors
What is the difference between early antral follicles and Larger antral follicles?
Early antral follicles - responsive to FSH, but considered to be FSH independent
Large antral follicles - Highly dependent on FSH for growth and survival
What factors promote atresia in oocytes and granulosa cells?
Tumor necrosis factor a (TNFa)
Androgens
IL-6
What are the two populations of granulosa cells that appear due to the swelling of the antral cavity?
Mural cells - close to thecal layer, engaged in steroidogenesis
Cumulus cells - surround oocyte, facilitate the capture of the oocyte by the ciliated fallopian tubes
What is the gonadotropin-dependent phase of follicular growth?
Cohort of growing antral follicles is recruited, but only dominant follicle survives
Survival of follicles that enter this stage of rapid growth is dependent upon FSH
When does cyclic recruitement occur?
During the late luteal phase of the preceding cycle
When is the dominant follicle selected?
Early follicular phase of the current cycle
What indicates the presence of a dominant follicle?
Dramatic increase in circulating estradiol levels
Ovulation occurs about 10-14 days after a follicle is selected
What is the role of FSH during the follicle selection process?
FSH stimulates granulosa cell proliferation and estradiol synthesis
Estradiol works syntergistically with FSH to promote granulosa cell proliferation
Estradiol and inhibit have a negative feedback effect on FSH release by the anterior pituitary
How does the dominant follicle inhibit the development of less mature follicles in the cohort?
Through the negative feedback by E2 on FSH release
The other follicles will undergo atresia
FSH containes within the follicular fluid of the dominant follicle helps it sustain the falling FSH levels
Why can granulosa cells respond to the LG surge?
FSH induces the expression of LH receptors
What factors influence the growth of the dominant follicle in the presence of declining levels of FSH?
More FSH receptors
Produces IGF-1, enhancing responsiveness to FSH
FSH induces LH receptor expression
Follicular fluid has FSH
Better developed vascular supply
What is the stigma?
Poorly vascularized bulge in the ovary created by the pressure of the follicle
What is cumulus expansion?
Increase in size of the cumulus-oocyte complex due to secretion of ECM components in response to LH stimulation
What s the signal required to induce ovulation?
LH surge
Result of a positive feedback effect of estradiol on the pituitary and hypothalamus
What are the specific actions of LH on the preovulatory follicle?
Release of hydrolytic enzymes
Expression of COX-2 and progesterone receptors
Resumption of meiosis via growth factor release
Promotes cumuls expansion
Promotes reorganization of follicle into the corpus luteum
What is the corpus luteum formed from?
Remnants of the ruptured follicle
Mural granulosa cells and thecal cells differentiate into granulosa- and thecal-lutein cells
How does LH promote angiogenesis?
Inducing the granulsa-lutein cells to secrete VEGF
Why are granulosa-lutein cells able to obtain cholesterol from circulating LDL and HDL?
LH induces breakdown of basal lamina
LH induces LDL and HDL receptor expression
How does LH induce steriodogenesis in granulosa-lutein cells?
Induces expression of StAR
Since these cells do not express androgen synthesis enzymes, they release progesterone
What causes luteolysis?
Decline in LH production due to negative feedback effects of estrogen and progesterone
What occurs to the corpus luteum in pregnant women?
Corpus luteum is maintained due to human chorionic gonadotropin (hCG)
