In the pro-oestrus stage of the Follicular Phase, is the level of oestrogen rising or falling?
In the pro-oestrus stage, oestrogen levels are rising. Oestrogen is made by conversion of androgens in the granulosa cells.
The androgens are made in the theca cells under control of the gondadotrophin LH, which is produced by gonadotroph cells of the anterior pituitary.
FSH, also synthesized by the anterior pituitary, induces the granulosa cells to convert the androgens to oestradiol-17ß.
Both FSH & LH are produced under the control of GnRH, produced by the neurons of the hypothalamus.
At the pro-oestrus, very early stage of the follicular phase, what impact does oestradiol-17ß have on the hypothalamus?
Oestradiol 17ß, aka E2, provides POSITIVE FEEDBACK to the hypothalamus to produce more GnRH, which induces the gonadotrophs of the anterior pituitary to release LH & FSH.
In the early, pro-oestrus stage of the follicular phase, what is the level of progesterone?
Progesterone levels in the early follicular phase are falling, since the corpus luteum from the previous cycle has been regressing.
So in the early, pro-oestrus stage of the follicular phase, there is rising oestrogen level and a falling progesterone level.
What are the oestadiol levels during the oestrus phase of the follicular phase?
The oestrus phase is the end of the follicular phase, usually just before ovulation.
The oestrus phase is characterised by maximal oestradiol-17ß plasma concentration made by granulosa cells, now almost solely under control of LH (FSH will no longer exert any impact in folliculogenesis).
A surge in LH, induced by the positive feedback of oestrogen, eventually causes ovulation.
After the Follicular Phase, which starts with pro-oestrus and ends with the end of oestrus, begins the Luteal Phase. Met-oestrus & Dioestrus occur within the Luteal Phase.
What are the plasma concentrations of oestrogen & progesterone during the metoestrus stage of this post-ovulatory phase?
Metoestrus: Oestrogen levels are falling sharply because the rising levels of progesterone -- secreted by the theca-lutein & granulosa lutein cells of the corpus luteum -- send NEGATIVE feedback to the hypothalamus that results in the reduction GnRH, thus reduction especially of LH & FSH secretion by the anterior pituitary.
Dioestrus: Consistently high level of secretion of progesterone by CL. Oestradiol levels very low because of negative feedback by progesterone to GnRH, FSH & LH.
In folliculogenesis, there are two basic stages of development, pre-antral and antral.
What characterises the pre-antral stage in terms of hormone levels?
Pre-antral: There are falling levels of progesterone, since the CL has been regressing, so there is no negative feedback on GnRH, which induces the release of FSH & LH from the anterior pituitary.
At this early stage, a quiescent follicle containing an ovum/oocyte becomes "committed", growing from primordial to primary follicle. Some atresia of follicles occurs in the ovaries.
Primordial follicle characterised by flat granulosa cells
Primary follicle is characterised by cuboidal granulosa cells.
FSH is not needed at the pre-antral stage.
What are the three substages that occur during the antral phase of folliculogenesis?
The antral stage is comprised of several sub-stages culminating in the dominance of a follicle(s) that will ovulate.
Th substages are:
Recruitment, Selection & Dominance.
What are the key hormonal levels in the antral stage, starting with Recruitment?
Recruitment is the first antral stage is coincides with "early Follicular". It is also "inter-cycle" (between luteal & follicular phases).
For some reason, as progesterone declines at the end of the luteal phase due to CL regression -- removing the negative feedback to the hypothalamus -- FSH SELECTIVELY rises.This "intercycle FSH rise" enables follicles to be recruited and for atresia to be low. Granulosa cells are not secreting inhibin yet; there LOW LH; and there is no oestradiol synthesized yet by the granulosa cells.
What are the key hormonal levels in the SELECTION stage of the antral phase?
Recruited antral follicles grow and start to develop LH receptors. The follicles also develop the enzyme aromatase, which converts androgens in theca cells to oestradiol in granulosa cells.
At this stage, the follicles are gonadotrophin (LH)-sensitive, but not gonadotrophin-dependent.
FSH is now falling/low, because of NEGATIVE FEEDBACK by oestrogen and inhibin secreted by granulosa cells.
LH levels are rising. Oestrogen is rising.
What are the hormonal levels during the DOMINANCE stage of the antral stage in folliculogenesis?
This is when the follicle becomes gonadotrophin-dependent. Only the follicles with LH receptors will become dominant.
In monotocous animals, a single follicle becomes dominant. In polytocous, several become dominant.
Follicles that only have FSH receptors become atresic, as FSH is no longer made in this stage due to negative feedback by oestradiol & inhibin.
The dominant follicles become dependent on LH for ovulation.
As oestradiol levels reach peak concentration, oestradiol switches over to providing POSITIVE FEEDBACK, inducing an LH surge, which triggers ovulation.
After oestradiol induces the LH surge through positive feedback in the hypothalamus during late follicular phase (after dominance in the antral phase), what are the hormone levels of those responsible for folliculogenesis (LH, FSH, oestradiol, progesterone) and those that are responsible for ovulation?
LH is HIGH in LH SURGE caused by positive feedback to hypothalamus of oestrogen
Oestrogen is HIGH, having reached threshold concentration to switch from negative feedback to positive feedback
FSH has been low, & might get an uptick from positive feedback by oestrogen, but has no impact on ovulation because dominant follicles only have LH receptors.
Important hormones / factors for ovulation: PGF2a (constrictive & most important) & PGE2 (dilatory)
↑ in PGF2a → contraction or ovarian smooth muscle → ↑ follicular wall pressure → ovulation
↑ in PGF2a → release of lysosomal enzymes → follicle wall weakens → ovulation
↑ in PGE2 - ↑ blood-flow to ovary → oedema → ↑ follicular wall pressure → ovulation
↑ blood-flow to ovary → oedema → ↑ follicular wall pressure → ovulation
Shift from oestradiol (E2) to progesterone (P4) → ↑ P4→ ↑ collagenase → follicle wall weakens → ovulation
What causes luteolysis / regression of CL? What happens?
CL secretes oxytocin → oxytocin travels in blood to bind to OTR in uterus → ↑ in PGF2α production by uterus → PGF2α, which has short half-life, travels back via uterine vein toward heart ∴ vein has high [PGF2α] → ovarian artery has low [PGF2α], but is wrapped around uterine vein, and thus PGF2α diffuses across into artery due to counter-current transfer → [PGF2α] travels in ovarian artery to CL → luteolysis