PHGY 210 Lecture Notes - Lecture 5: Granulosa Cell, Progesterone Receptor, Endometrium

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Published on 28 Nov 2015
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Course
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Phgy 210
January 14, 2015
Endocrinology Lecture 5
The Menstrual Cycle
Prior to day one, endometrium thickens under influence of
estradiol
Progesterone induces the appearance of specialized glycogen-
secreting glands
Day 1 first day of detectable vaginal bleeding deterioration of
uterine endometrium
Menses (bleeding) begins when estradiol and progesterone very
low in circulation, when the blood vessels supplying
endometrium constrict reducing the blood supply
Endometrium deteriorates, flows through the cervix into the
vagina
Bleeding occurs for ~5 days during which, ovaries are
endocrinologically rather inactive
Low estradiol and progesterone leads to increased pituitary FSH
secretion (lack of ve feedback loop)
Also, decrease in non-steroidal ovarian inhibin which selectively
inhibits secretion of FSH, may contribute to elevation in FSH
release
Under influence of FSH, cohort of ovarian follicles develop. FSH stimulates granulosa cells of follicles
to proliferate production of estrogen, which further stimulates granulosa cell proliferation
Day 8, one follicle becomes dominant and committed to further development. Remaining follicles
begin to degenerate by atresia. In humans, how one follicle becomes dominant still unknown
Dominant follicle produces increasingly more estradiol, which becomes important in late stages of
cycle
Increasing estradiol stimulates uterine endometrium proliferation
By day 13, the endometrium very thick, estradiol induces production of endometrial progesterone
receptors
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Phgy 210
January 14, 2015
Estradiol effects on brain and pituitary
Moderate estradiol concentrations:
Negative feedback on FSH release
Stimulate synthesis of LH by pituitary and increase sensitivity of pituitary to GnRH stimulates LH
synthesis
Although moderate estradiol concentrations stimulate LH synthesis, they inhibit LH release.
Therefore, LH accumulates to high levels within pituitary
High estradiol concentrations:
Under influence of developing follicle, estrogen concs. continue to build
Elevated estrogen concs. stimulate LH release LH surge ~day 14 (small increase in FSH release also
occurs)
Stimulation of LH synthesis by estradiol and increased sensitivity of the anterior pituitary to GnRH
leading to increased LH synthesis by anterior pituitary known as estrogen +ve feedback control
mechanism
Thus, estrogens exert ve feedback decreased GnRH and LH release and +ve feedback increased
sensitivity of anterior pituitary cells to GnRH and increased LH synthesis
Meanwhile, at the ovary the follicle has become huge. The sudden surge of LH causes the follicle to
rupture (mechanism unclear) and the ovum is ejected
Feedback mechanisms of steroid hormones on gonadotropin action:
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Phgy 210
January 14, 2015
Oral Contraceptives
Pills contain estrogen and progesterone maintain moderate circulating levels of estrogen and
progesterone, suppress the release of LH and FSH from the pituitary and prevent ovarian follicles
from maturing and being ovulated
99% success, provided that the pill is taken daily for 21 consecutive days with seven days of no
medication that would induce menstruation
Corpus Luteum
Under the influence of LH, the follicle becomes corpus luteum produces large amounts of estradiol
and progesterone induce endometrial growth of the uterus.
In addition, under the influence of progesterone, the endometrium becomes glandular.
The endometrium is now fully prepared to receive and support the development of a growing
embryo
Luteal Phase
No fertilization egg degenerates, corpus luteum degenerates (luteolysis)
Lasts a constant 14 days, known as the luteal phase of cycle since steroids produced by corpus
luteum dominate
After 14 days in absence of implantation, corpus luteum degenerates, steroid levels drop, uterine
endometrium degenerates, menstruation begins, and pituitary starts to increase its secretion of
FSH, and we are back to the beginning of the cycle
Fertilization and implantation
At ovulation, unfertilized egg is taken by the fimbria of the oviduct
(or fallopian tube) and is being propelled towards the lumen of the
uterus
If sexual intercourse takes place around this time, some
spermatozoa deposited in the vagina will travel as far as the
oviduct and one of these will fertilize the egg
Egg starts dividing to the stage of blastocyst during its transport
down the oviduct into the uterine lumen
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Document Summary

Prior to day one, endometrium thickens under influence of estradiol. Progesterone induces the appearance of specialized glycogen- secreting glands. Day 1 first day of detectable vaginal bleeding deterioration of uterine endometrium. Menses (bleeding) begins when estradiol and progesterone very low in circulation, when the blood vessels supplying endometrium constrict reducing the blood supply. Endometrium deteriorates, flows through the cervix into the vagina. Bleeding occurs for ~5 days during which, ovaries are endocrinologically rather inactive. Low estradiol and progesterone leads to increased pituitary fsh secretion (lack of ve feedback loop) Also, decrease in non-steroidal ovarian inhibin which selectively inhibits secretion of fsh, may contribute to elevation in fsh release. Under influence of fsh, cohort of ovarian follicles develop. Fsh stimulates granulosa cells of follicles to proliferate production of estrogen, which further stimulates granulosa cell proliferation. Day 8, one follicle becomes dominant and committed to further development. In humans, how one follicle becomes dominant still unknown.

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