1.5.2 Female Endocrinology, Pt 1

Question 1

As the follicle grows in the ovary there is increased secretion of?

Answer 1

Inhibin and estradiol

produced by granulosa cells

Question 2

Within theca cells what is the product that is transferred to the granulosa cell? What does the granulosa cell use this to create?

Answer 2

Androstendione

Granulosa cell uses it to create estradiol

Question 3

What is the role of Kisspeptin?

Answer 3

Stimulatory effects of GnRH

Question 4

What are the functions of androgens?

Answer 4

Question 5

What is the function of the ovary?

Answer 5

Folliculogenesis - oocyte maturation

Hormone synthesis/secretion

Question 6

What is the role of Estradiol on GnRH-r?

Answer 6

Increases it

Question 7

Describe steroid secretion by the ovary over the course of the menstrual cycle

Answer 7

Question 8

What is the role of estrogen vs progesterone at the level of the mammary gland and other sites?

Answer 8

Question 9

Draw the basic pituitary axis for FSH and LH

Answer 9

Question 10

What is the role of GnRH?

Answer 10

It stimulates LH and FSH release from the anterior pituitary

Question 11

What is the role of estrogen and progesterone at the level of the hypothalamus/pituitary?

Answer 11

Estrogen - negative feedback, positive feedback, stimulates prolactin, behavior

Progesterone - Negative feedback

Question 12

What is the role of activins?

Answer 12

Stimulation of FSH secretion

Question 13

What is the role of the inhibins?

Answer 13

Inhibit FSH secretion at the pituitary

Question 14

What is the two cell theory in regards to ovarian steriodogenesis?

Answer 14

Theca cells:

1. Androgen production under the control of LH (increases cholesterol movement, SCC, 17alpha-OH and 17-20 desmolase)
2. No aromatase activity
3. Insulin/IGF-1 can induce expression of the LH receptor and its signaling

Granulosa cells:

1. Estrogen (estradiol) production under the control of FSH (induces aromatase activity; no 17alpha OH activity)
2. Requires androgens as a substrate (provided by Theca cells)

Question 15

What are the functions of the estrogens?

Answer 15

Question 16

Estrogen positive feedback is critical for?

Answer 16

Ovulation

Question 17

During the follicular phase what is the role of FSH and estradiol?

Answer 17

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

Question 18

What is the signaling pathway for GnRH in the pituitary?

Answer 18

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.

Question 19

Draw the chart of the hormones

Answer 19

Question 20

What is the role of follistatin?

Answer 20

Binds and inhibits activins

Question 21

What are the functions of progesterone?

Answer 21

Question 22

What is occuring during the gonadotropin surge at ovulation?

Answer 22

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.

Question 23

What increases and decreases CBG and SHBG production in the liver?

Answer 23

Increased - Estrogens

Decreased - androgens

Question 24

Describe gonadal feedback regulation of LH and FSH secretion

Answer 24

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.

Question 25

What is the function of FSH on the ovary?

Answer 25

Stimulates growth of follicles and estrogen synthesis and secretion

Question 26

FSH is mediated by what signaling pathway?

Answer 26

cAMP/protein kinase A signaling pathway

Question 27

What is the signaling pathway that mediates LH function?

Answer 27

cAMP and PKA pathway

Question 28

What is the role of estrogen and progesterone at the level of the uterus?

Answer 28

Estrogen - proliferation, myometrium Progesterone - development of glands and vasculature, myometrium and decidua cells

Question 29

Fill in this chart

Answer 29

Question 30

What is the role of FSH and LH on the ovary during the different points of the menstrual cycle?

Answer 30

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)]

Question 31

Describe the pathway of steroidogenesis in the ovary

Answer 31

Question 32

What is the role of estrogen on arcuate vs AVPV neurons?

Answer 32

Question 33

What are the KNDy neurons?

Answer 33

Neurons withing the arcuate that express: Kisspeptin Neurokinin B Dynorphin

Question 34

The corpus luteum is created by?

Answer 34

Ovulation of the ooctye

Question 35

What is the role of CBG and SHBG?

Answer 35

CBG - binds glucocorticoids, aldosterone and **progesterone** SHBG - Binds sex steroids

Question 36

What is the role of LH on the ovary?

Answer 36

Stimulates ovulation of mature follicle and formation of corpus luteum; stimulates estrogen and progesterone synthesis and secretion by corpus luteum