Physiology Flashcards
What changes occur in preparation for ovulation?
- the pH in the vagina becomes less acidic,
- the cervical mucus becomes more copious and less viscous
- the cervical os becomes more patulous, all of these changes favor the progress of motile sperm towards the released oocyte.
Describe the hypothalamo pituitary ovarian axis
GnRH released by hypothalamus
Goes to anterior pituitary to release gonadotrophins: FSH and LH
Induces the production of estradiol and progesterone from the ovary which, in turn, through a feedback mechanism, influence the pattern of release of GnRH from the hypothalamus
GnRH
Released in a pulsatile fashion
Mostly in response to oestrodiol
Also influenced by: opiates, catecholamines, neuropeptide Y, etc
If released constantly then gonadotrophin release is suppressed due to downregulation of receptors in pituitary
Hormonal changes during menstrual cycle
https://www.glowm.com/section_view/heading/the-mechanism-of-ovulation/item/289 for rest of the q
What is the role of FSH?
- Granulosa cell proliferation and differentiation
- Antral follicle development
- Estrogen production
- Induction of LH receptors on the dominant follicle
- Inhibin synthesis
Declining secretion of FSH prevents multiple follicular development, as only the largest of the developing follicles stays above the FSH threshold, has the most FSH receptors, remains most sensitive to FSH and produces most estrogen.
It is then less sensitive to the declining FSH concentrations and can continue to develop while others fade into atresia due to lack of enough FSH stimulation.
The induction of LH receptors on the largest developing follicle(s) enables LH to take a part in the development of the dominant follicle in the late follicular phase and prepare it for the oncoming LH surge
What happens to LH levels during cycle?
Initially low levels of LH in early and mid follicular phase. Just small pulses.
Then a big surge of LH over 36-48 hours which induces ovulation
Cause of LH surge:
- Switch from a negative to a positive feedback action of estradiol at both the pituitary and hypothalamic level,
- Triggered when persistently increasing estradiol concentrations reach a critical point.
- LH secreting pituitary gonadotrophs become highly sensitive to GnRH stimulation, by increasing their numbers of GnRH receptors, a GnRH surge occurs and a small rise in progesterone levels in the late follicular phase may also have a triggering role.
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Purpose of the LH surge
- Triggering of ovulation and follicular rupture about 36 hours after the surge.
- Disruption of the cumulus–oocyte complex.
- Induction of the resumption of oocyte meiotic maturation.
- Luteinization of granulosa cells
Following the formation of the corpus luteum, increasing concentrations of progesterone slow down the frequency of the LH (GnRH) pulses to one every 3 then one every 4 hours. Concentrations of LH once again dip down to baseline levels.
HCG can be used as a replacement for LH in fertility treatment as it binds to the LH receptors but has a longer half life
Role of LH and FSH outside of surge
Encourage the production of androgens by theca cells
Androgens then ‘passed on’ to granulosa cells
Aromatase converts androgens to oestrogens
Action of converting androgens to oestrogens controlled by FSH
Key function of oestrodiol in ovulatory cycle
- As a cog in a negative feedback mechanism suppressing the secretion of FSH and so aiding in the selection of the dominant follicle and preventing multifollicular development in the mid-late follicular phase.
- Triggering of the LH surge in mid-cycle by initiating a positive feedback mechanism when its concentrations rise to a critical level.
- As a ‘growth hormone’ for the development of the endometrium.
Estradiol concentrations are at their lowest during menstruation.
Pattern of oestrogen in cycle
Estradiol concentrations are at their lowest during menstruation.
The FSH induced follicular development brings about rapidly rising estradiol production in the mid-follicular phase.
When estradiol levels attain a persistently high critical concentration in the late follicular phase, they induce the LH surge.
Following ovulation, estradiol concentrations dip temporarily but are revived by corpus luteum activity.
With the demise of the corpus luteum, estradiol concentrations sink rapidly to their lowest levels and invoke the FSH rise immediately preceding menstruation
Hormonal changes in hypogonadotrophic hypogonadism
Both FSH and LH secretion are essentially missing
The absence of FSH results in a lack of follicular development and estrogen production and the absence of LH in a lack of androgen substrate production.
When treatment with pulsatile GnRH is administered, pure substitution therapy, everything falls into place and ovulation can be successfully induced.
If pure FSH is used to induce ovulation by direct stimulation of the ovaries, the lack of LH and therefore lack of production of androgen substrate, allows the growth of follicles but not estradiol production.
Even if ovulation can be triggered by hCG or recombinant LH when a large follicle is obtained, implantation cannot occur due to the lack of estrogen stimulation on the endometrium.
Pattern of progesterone
Progesterone is produced by luteinized granulosa cells.
Large quantities are synthesized by the corpus luteum following ovulation.
Progesterone concentrations rise to a peak 7–8 days following ovulation and fall rapidly with the failure of the corpus luteum.
The main function of progesterone from the corpus luteum is to fashion a secretory endometrium, capable of hosting the implantation of an embryo and to maintain this endometrium throughout the early weeks of pregnancy until trophoblastic/placental hormones take over this role.
Under the influence of progesterone the endometrial glandular structures increase greatly in numbers and become more tortuous. Progesterone also plays a role in the expression of genes needed for implantation at the level of the endometrium.
Together with estradiol, progesterone suppresses pituitary gonadotropin release during the luteal phase. The increasing concentrations of progesterone following ovulation gradually reduce the frequency of the GnRH/LH pulses and increase their amplitude.
During this phase, FSH is synthesized and stored ready for release when freed from the inhibition imposed by progesterone and estradiol when the corpus luteum fails.
The initial rise of progesterone concentrations immediately preceding the LH surge may play a role in the triggering of this surge.
Ovarian morphology
Morphology of an antral follicle
