Abstract
The ability of ovarian follicles to produce large amounts of estradiol is a hallmark of follicle health status. Estradiol producing capacity is lost in ovarian follicles before morphological signs of atresia. A prominent wave like pattern of growth of antral follicles is characteristic of monotocous species such as cattle, horses and humans. While our knowledge of the role of pituitary gonadotropins in support of antral follicle growth and development is well established, the intrinsic factors that suppress estradiol production and may help promote atresia during follicular waves are not well understood. Numerous growth factors and cytokines have been reported to suppress granulosa cell estradiol production in vitro, but the association of expression of many such factors in vivo with follicle health status and their physiological significance are not clear. The purpose of this review is to discuss the in vivo and in vitro evidence supporting a local physiological role for cocaine and amphetamine regulated transcript, inhibins and low molecular weight insulin like growth factor binding proteins in negative regulation of granulosa cell estradiol production, with emphasis on evidence from the bovine model system.
Highlights
Folliculogenesis is generally defined as the formation of mature preovulatory follicles (Graafian) from the pool of primordial follicles
Atresia of dominant follicles during non-ovulatory follicular waves is crucial for the timely development of ovulatory waves during the follicular phase of menstrual and estrous cycles in monoovulatory species like humans and cattle
Development of a single dominant ovulatory follicle from the cohort of growing follicles depends on the timely atresia of all subordinate follicles during waves
Summary
Folliculogenesis is generally defined as the formation of mature preovulatory follicles (Graafian) from the pool of primordial (non-growing) follicles. Messenger RNA for the inhibin co-receptor betaglycan is greater in granulosa cells of subordinate versus dominant follicles collected near the time of deviation (3 days after emergence) of the first follicular wave in cattle [98] , suggestive of a potential role for betaglycan regulation in control of inhibin mediated antagonism of activin action resulting in reduced estradiol production in subordinate follicles. Above described negative relationship between follicular fluid estradiol and inhibin concentrations, enhanced expression of betaglycan mRNA in granulosa cells of subordinate versus dominant follicles, and direct effects of α2-macroglobulin (the inhibin binding protein) and inhibins on bovine granulosa cell estradiol production observed in vitro are supportive of a potential local physiological role for inhibins in negative regulation of granulosa cell estradiol production during follicular waves in cattle. Whether the negative effects of CART on bovine granulosa cell estradiol production are mediated via inhibition of L-type calcium channel activity or are calcium independent and mediated via a putative CART receptor is a subject for future investigation, as are the factors that regulate granulosa cell CART expression during follicular waves
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