Female Reproductive Endocrinology I week 4 Flashcards
What is the secretory gland for estrogen release?
What cell(s) secrete estrogen?
What hormones stimulate estrogen release? What cell(s) do these hormones act on?
How is estrogen transported in blood?
What is the mechanism of action of estrogen?
What is the biological response of estrogen?
What glands release progesterone?
adrenal cortex, ovaries, placenta during pregnancy
What cell(s) in the ovary secrete progesterone?
How is progesterone transported in blood?
What is the mechanism of action of progesterone?
What is the biological response of progesterone?
What gland secretes inhibin in females?
What cell(s) secrete inhibin?
What is the chemical class of inhibin?
What hormone stimulates inhibin release?
What is the mechanism of action of inhibin?
What is the biological response of inhibin?
How long is the reproductive cycle?
What are the 3 phases of the reproductive cycle and approximately when do they occur?
28 day cycle
Is variable across a population
Individual’s cycle length variable
Cycling begins at puberty
Describe the process of oogenesis.
Primordial germ cells give rise to oogonia. Beginning at 8 to 9 weeks of fetal development and continuing until 6 months after birth, the oogonia begin, but do not complete, the first meiotic division. 4. They are now known as primary oocytes. Primary oocyctes are arrested in prophase of meiosis I. At ovulation, primary oocytes complete meisosis I and are arrested in metaphase of meiosis II. At this stage, they are referred to as secondary oocytes. With each meiotic division (2 total) a polar body is formed. Polar bodies have the same genetic material as oocytes but have much less cytoplasm. They have no function and eventually degenerate.
How many oogonia are in ovaries in the fetus?
By the time a fetus is born, how many oocytes remain?
At onset of puberty, how many oocytes are in ovaries?
Prior to puberty, what process causes a decrease in the number of oocytes? What causes this after puberty?
Primordial germ cells give rise to oogonia; by 20-24 weeks of fetal development there are 7 million oogonia in the ovaries. Beginning at 8 to 9 weeks of fetal development and continuing until 6 months after birth, the oogonia begin, but do not complete, the first meiotic division (now known as primary oocytes). At the same time a process of attrition begins so that at birth there are approximately 2 million oocytes remaining and by the onset of puberty only a few hundred thousand (100,000 – 400,000) are left.
Between birth and the onset of puberty primary oocytes mature in a continuous (non-cyclic) manner and independently of gonadotropins. All of these developing oocytes undergo atresia (degeneration or apoptosis). Following the onset of puberty, follicles mature, and either degenerate or ovulate in a cyclical manner. However, only a very small number of follicles mature during the reproductive years of the woman. Ova that ovulate (are released) are either fertilized (pregnancy follows) or not. In the end, only approximately 400-500 oocytes have the potential to be fertilized.
The primary phase of follicular development (from primordial to secondary follices) takes place continuously in females until when?
What changes to the follicle occur during this period?
What hormones stimulate this process?
About how many days does this process take?
Primary phase of follicular development takes place continuously until menopause: a cohort of primordial follicles is recruited (stimulus unknown) to develop into secondary follicles.
a. follicle increases in diameter (from 20 to 400 microns) mostly due to increase size of primary oocyte.
b. there is increased synthetic (metabolic) activity and morphological changes
c. meiosis is NOT yet reactivated
d. this is part of the repackaging process of gametogenesis
e. granulosa cells divide to form several layers and secrete glycoprotein to form the zona pellucida between themselves and the oocyte
f. cells in ovarian stroma become condensed to form the theca
g. these developments occur independently of the presence of gonadotropins (in the absence of significant concentrations of LH and FSH)
h. this phase takes at least 120 days
During the second phase of follicular development, the secondary follicles continue their developement into antral follicles.
What changes occur to the follicle during this stage?
What hormones is this process dependent upon?
Prior to the onset of puberty, what happens to follicles that reach the end of this phase?
During the second phase (which requires 65 days) the secondary follicles continue their development into antral follicles. These stages are also independent of gonadotropins.
a. granulosa and thecal cells continue to proliferate, therefore further increase in size of follicle. However, oocyte stays about same size.
b. division of theca to:
i. theca interna - glandular and vascularized
ii. theca externa - fibrous capsule
c. fluid droplets secreted by granulosa cells appear and fill the follicular antrum (cavity at center of the follicle)
d. Prior to the onset of puberty all follicles that reach the end of this phase undergo apoptosis
With the onset of puberty and the increased concentrations (and cyclic changes in concentrations) of gonadotropis a relatively small amount of antral follicles are recruited to continue their development.
During recruitment, what strucutre connects the ovum to the follicle?
What hormones does the follicle secrete at this time? What cells secrete which hormones?
How long is this phase of development?
a. the ovum becomes attached to the follicle by a thin stalk and is surrounded by the cumulus oophorus, a dense mass of granulosa cells
b. follicle secretes androgens and estrogens and inhibin
c. the theca interna secretes androgens under LH stimulation
d. the granulosa cells aromatize these androgens to estrogen under FSH stimulation
e. This phase of develop takes 5-7 days to take place
What is the local intrafollicular role of estrogen in nthe recruitment phase?
How does the intrafollicular role of estrogen lead to increased estrogen levels?
local intrafollicular role of steroids
i. estrogens cause proliferation of granulosa cells and increase synthesis of more estrogen receptors
ii. this positive feedback is partly responsible for the rising levels of estrogen seen at the end of this phase
iii. estrogens, along with FSH, stimulate appearance of LH- binding sites on outer layers of granulosa cells.
What is the likely reason that a follicle is dominant over the other developing follicles?
What are the effects of estrogen released by dominant follicles?
A dominant follicle is “selected” probably as a result of having more receptors for FSH than others in the cohort; its development eventually causes the death of other antral stage follicles in the cohort.
The dominant follicle likely has more granulosa cells: more sensitive to FSH. Estrogen released feeds back and inhibits FSH release. The dominant follicle that is most sensitive to the low levels of FSH still develops. The other nondominant follicles cannot develop with low FSH levels.
Explain/summarize the affects of FSH and LH on granulosa and theca cells during early and late follicle development prior to ovulation.
Explain the change in repsonse of the hypothalmus and pituitary to estrogen during early and late follicle development prior to ovulation.
Explanation of attached figure:
The gonadotropins, LH and FSH, are released from the pituitary when it is stimulated by GnRH. LH and FSH act on the ovaries to stimulate the production of estrogen.
(1) FSH stimulates granulosa cells to increase production of estrogen.
(2) Local estrogen stimulates granulosa cells (autocrine function) to make more receptors for estrogen and FSH. This results in the granulosa cells making still more estrogen. This is an example of positive feedback. The increasing concentration of estrogen exerts a negative feedback effect on the hypothalamus and the pituitary.
(3) Later during this developmental process, FSH causes an increase in LH receptors in granulosa cells and they become more responsive to LH.
(4) LH stimulates androgen production by thecal cells. The increased androgen is used by granulosa cells to increase production of estrogen. (LH simultaneously stimulates the granulosa cells to make more progesterone.)
(5) As an antral follicle becomes the dominant follicle it secretes estrogen at a faster and faster rate, rapidly increasing the concentration of circulating estrogen.
(6) Rising estrogen concentration exerts a positive feedback on the hypothalamus and pituitary to produce the pre-ovulatory surge of LH and FSH.
For ovulation to occur, a brief surge in gonadotropins is required.
What are the results of the LH surge? (what happens to oocyte, changes in hormones secreted, etc.)
How long is the ovulatory phase?
- For this phase to proceed a brief surge of gonadotropins is required (see next section for a description of the mechanisms responsible for the cycling of hormones and the LH surge)
- LH surge results in:
a. oocytes completing the remainder of first meiotic division
i. polar body gets 2 of the chromosomes and is discarded; the other cell gets 2 of the chromosomes and all the cytoplasm.
ii. meiosis is then again arrested and ovulation occurs.
b. further increase in follicular size due to prostaglandins (PGs) that promote vascular changes that cause swelling. (FIG. 11-attached) - Within 2 hours of LH surge, there is an increase in estrogen and androgen production which then declines to very low levels
- Granulosa cells start producing progesterone
- The expansion of granulosa cells during the preovulatory phase causes follicle to bulge out of ovary
- at ovulation the follicle bursts (as a result of increased secretion of prostaglandins and swelling of the follicle and PG induced enzymatic digestion of follicular wall), and the oocyte (with its cumulus oophorus) escapes (FIG. 11)
- the fimbria of the oviduct sweep the egg into the oviductal ostium
- this phase lasts about 37 hours.
What is the ruptured follicle converted into after ovulation?
corpus luteum