1.5.2 Female Endocrinology, Pt 1 Flashcards
As the follicle grows in the ovary there is increased secretion of?
Inhibin and estradiol
produced by granulosa cells
Within theca cells what is the product that is transferred to the granulosa cell? What does the granulosa cell use this to create?
Androstendione
Granulosa cell uses it to create estradiol
What is the role of Kisspeptin?
Stimulatory effects of GnRH
What are the functions of androgens?
What is the function of the ovary?
Folliculogenesis - oocyte maturation
Hormone synthesis/secretion
What is the role of Estradiol on GnRH-r?
Increases it
Describe steroid secretion by the ovary over the course of the menstrual cycle
What is the role of estrogen vs progesterone at the level of the mammary gland and other sites?
Draw the basic pituitary axis for FSH and LH
What is the role of GnRH?
It stimulates LH and FSH release from the anterior pituitary
What is the role of estrogen and progesterone at the level of the hypothalamus/pituitary?
Estrogen - negative feedback, positive feedback, stimulates prolactin, behavior
Progesterone - Negative feedback
What is the role of activins?
Stimulation of FSH secretion
What is the role of the inhibins?
Inhibit FSH secretion at the pituitary
What is the two cell theory in regards to ovarian steriodogenesis?
Theca cells:
- Androgen production under the control of LH (increases cholesterol movement, SCC, 17alpha-OH and 17-20 desmolase)
- No aromatase activity
- Insulin/IGF-1 can induce expression of the LH receptor and its signaling
Granulosa cells:
- Estrogen (estradiol) production under the control of FSH (induces aromatase activity; no 17alpha OH activity)
- Requires androgens as a substrate (provided by Theca cells)
What are the functions of the estrogens?
Estrogen positive feedback is critical for?
Ovulation
During the follicular phase what is the role of FSH and estradiol?
Follicle stimulating hormone (FSH): granulosa cells are targets
a. FSH stimulates the conversion of androgens to estrogens (aromatization)
b. FSH stimulates granulosa cell proliferation and follicular growth
c. FSH stimulates granulosa cell inhibin, activin,& follistatin synthesis
d. FSH induces LH receptors on granulosa cells of preovulatory follicles
What is the signaling pathway for GnRH in the pituitary?
GnRH activates G alpha q which will in turn activate PLC. PLC will go on to activate PKC and Ca++. Increases in these will result in the release of LH and FSH.
Draw the chart of the hormones
What is the role of follistatin?
Binds and inhibits activins
What are the functions of progesterone?
What is occuring during the gonadotropin surge at ovulation?
Gonadotropin regulation of the Ovary
Approximately 36-48 hr prior to Ovulation there is an increase in Estradiol secretion that initiates positive feedback (hypothalamus and pituitary). These leads to:
LH surge (FSH also) – increased GnRH secretion and GnRH receptors (estrogen mediated events)
Proteolytic factors are produced within the follicle
Inflammatory response – increased prostaglandin release
Meiotic block is removed
These events are not seen in males (that is the positive feedback) due to androgenization of the brain.
What increases and decreases CBG and SHBG production in the liver?
Increased - Estrogens
Decreased - androgens
Describe gonadal feedback regulation of LH and FSH secretion
Negative Feedback. Steroid hormones produced in response to gonadotropin stimulation feedback at the hypothalamic (mediobasal hypothalamus) and anterior pituitary levels to reduce gonadotropin secretion. The inhibitory effect can be on both the frequency and amplitude of gonadotropin secretion. The effects of steroid hormones are much more prominent on LH release than on FSH release.
FSH secretion is also controlled by a peptide hormones termed inhibin and follistatin. These hormones are produced by the granulosa cells of the ovarian follicles and the Sertoli cells of the semineferous tubules of the testis. Inhibin and follistatin specifically inhibit FSH secretion while having no effect on LH secretion. The site of action of these hormones is at the anterior pituitary level.
Positive Feedback. The preovulatory surges of LH and FSH are stimulated by estrogen. Estrogen sensitizes the anterior pituitary to GnRH and also promotes the hypothalamic (preoptic nucleus) release of GnRH.
The ovary and testis also secrete a hormone, termed activin, that specifically stimulates the secretion of FSH. The physiological significance of this factor is presently unknown.
What is the function of FSH on the ovary?
Stimulates growth of follicles and estrogen synthesis and secretion
FSH is mediated by what signaling pathway?
cAMP/protein kinase A signaling pathway
What is the signaling pathway that mediates LH function?
cAMP and PKA pathway
What is the role of estrogen and progesterone at the level of the uterus?
Estrogen - proliferation, myometrium
Progesterone - development of glands and vasculature, myometrium and decidua cells
Fill in this chart
What is the role of FSH and LH on the ovary during the different points of the menstrual cycle?
Luteinizing hormone (LH)
a. Ovarian interstitial and theca cells are targets for LH. These cells possess LH receptors and respond to LH by producing androgens
b. Granulosa cells gain the capacity to respond to LH in preovulatory follicles
i. LH stimulates granulosa cell steroidogenesis
c. During the latter stages of follicular development:
i. LH removes the block of oocyte meiosis
ii. LH triggers ovulation. The process of ovulation is a complex phenomenon in LH initiates a cascade of events involving breakdown of the follicular basement membrane and elevation of prostaglandin biosynthesis leading to changes in vascular permeability
d. LH stimulates the formation of the corpus luteum
i. Luteal cells of the corpus luteum elaborate progesterone and some estrogen and are primarily dependent upon LH or LH-like proteins (chorionic gonadotropin, CG)
ii. Luteal cells also produce a peptide hormone termed relaxin (will be discussed later)
iii. Terms associated with the regulation of corpus luteum function:
luteotropic [stimulation of luteal function, LH, CG]
luteolytic [inhibition of corpus luteum function or stimulator of corpus luteum demise (prostaglandin F2a, oxytocin)]
Describe the pathway of steroidogenesis in the ovary
What is the role of estrogen on arcuate vs AVPV neurons?
What are the KNDy neurons?
Neurons withing the arcuate that express:
Kisspeptin
Neurokinin B
Dynorphin
The corpus luteum is created by?
Ovulation of the ooctye
What is the role of CBG and SHBG?
CBG - binds glucocorticoids, aldosterone and progesterone
SHBG - Binds sex steroids
What is the role of LH on the ovary?
Stimulates ovulation of mature follicle and formation of corpus luteum; stimulates estrogen and progesterone synthesis and secretion by corpus luteum
