Endocrine Feedback Mechanisms Flashcards
(43 cards)
Control of the reproductive hormones during the menstrual cycle is centered upon a delicate endocrine feedback mechanism between
the hypothalamus, the pituitary , and the ovarian hormones .
The gonadotropins stimulate estrogen and progesterone production that is controlled, in turn, through the actions of
estrogen and progesterone to suppress the tonic secretion of the gonadotropins.
This relationship between the gonadotropins and steroids is an example of a
classic endocrine negative feedback system.
The feedback regulation between the pituitary and ovary is very complex. In its simplest terms it can be viewed as involving the following sequence of events:
a. As the levels of the gonadotropins increase the production and release of estrogen and progesterone increases.
b. As the systemic concentrations of estrogen and progesterone increase these steroids begin to inhibit gonadotropin secretion that leads to a diminution in gonadotropin secretion.
c. The drop in gonadotropins would decrease the production of the steroids.
d. As the systemic concentrations of estrogen and progesterone decrease the negative inhibition of the gonadotropins is removed. Gonadotropin concentrations would increase again and the cycle of negative feedback control would repeat.
This oscillating cycle is the basis of the endocrine mechanism used to control the
menstrual cycle.
However, secretion levels of the sex steroids vary throughout the menstrual cycle due to
the constantly changing ovarian follicle development.
Furthermore, the inhibitory actions of estrogen and progesterone upon the gonadotropins differ:
- Estrogen inhibits the synthesis and release of LH at the level of the pituitary.
- Progesterone, on the other hand, appears to act primarily on the hypothalamus by decreasing the duration and amplitude of GnRH release.
The control of FSH secretion by steroids differs from LH in that the
tonic secretion of FSH is more sensitive to negative feedback by estradiol.
Therefore, small concentrations of estrogen can
selectively inhibit FSH release.
Pituitary FSH may also be controlled by non-steroidal ovarian hormones such as
inhibin, activin, follistatin and antimullerian hormone (AMH).
Activins, inhibins and AMH are structurally related proteins and are functionally antagonistic members of the
TGFB superfamily of extracellular signaling molecules.
Activin and inhibin are chemically composed of
two disulfide-linked dimers.
The dimers are peptide subunits designated as alpha and beta subunits. There are ___________ forms of activin and __________ forms of inhibin.
3, 2
Inhibins antagonize activin by
binding to receptors and preventing activin from forming active signaling complexes.
They can also antagonize BMP activity by
competing for endocrine receptor binding.
They are principally produced in the ovary by
the granulosa and thecal cells and selectively inhibit the secretion of FSH by the pituitary suggesting that inhibin plays a role in the ovarian negative feedback control of FSH secretion.
Somatic (thecal, granulosa, luteal) cells express the inhibin co-receptor
betaglycan.
The data available confirm that inhibin B is mainly produced in the follicular phase by pre- antral and small antral follicles, while inhibin A appears to
be the predominant form produced during the late follicular and luteal phases by preovulatory follicles and corpus luteum, respectively.
Early follicular phase inhibin B levels decrease with age, reflecting the increase in
early follicular phase FSH levels and recruitment of diminished cohorts of follicles with ovarian ageing. The roles of activin, follistatin and AMH are less clear.
Inhibin regulates FSH levels by preventing the
upregulation of GnRH receptors on pituitary gonadotropes.
Activins were first isolated from ovarian follicular fluid of cows and pigs and have pleiotropic reproductive and metabolic actions. They share 65% homology and overlapping biological activities but also display some divergent functions due to
differential expression and receptor utilization and affinities.
They are also produced by a wide range of extra-gonadal tissues and are primarily considered to act as
local autocrine and paracrine signaling molecules.
In the ovary, activins are recognized as important factors in
the induction and maintenance of the FSHR.
Activin A has been measured during the normal menstrual cycle with higher levels in the
early follicular phase, at midcycle, and in the late luteal phase suggesting that activin A may contribute to the increase in FSH levels during these particular periods.
