Autocrine/paracrine regulation of the ovarian follicle

Classically, the pituitary gonadotropins (i.e., follicle-stimulating hormon e and luteinizing hormone) and gonadal steroids (primarily estrogen) have b een assigned the role of primary regulators of the ovarian life cycle. As t he complexities of the process of follicular growth, maturation and ovulati on are elucidated, the inadequacies of this hypothesis have become evident. To better explain observed phenomena such as recruitment and se lection of the dominant follicle, a system of intraovarian regulators has been propos ed that would work in concert with gonadotropins and steroids amplifying, a ttenuating or even mediating gonadotropin action. These locally produced fa ctors are thought to function mainly through one of two pathways. In the pa racrine pathway, regulators diffuse locally from producer cells to distinct target cells within the same organ. In the autocrine pathway, the regulato r acts via surface receptors at its cell of origin. The list of putative au tocrine/paracrine regulators in the ovary is growing rapidly. To prioritize the potential physiological relevance of these factors, it has been sugges ted that to qualify as a bona fide intraovarian regulator, a candidate shou ld show evidence of local production, reception, action and some degree of indispensability to the process of follicular development and ovulation. Au tocrine/ paracrine regulators currently under study include the insulin lik e growth factor system, which appears to function as an amplifier of gonado tropin hormonal action. Also, there is the transforming growth factor-beta gene superfamily, which includes activin, inhibin and growth and differenti ation factor-9. Data suggest that activin and inhibin work in concert as at tenuators or amplifiers of gonadotropin action, and that growth differentia tion factor-9 is an oocyte specific growth factor that may be necessary for development to occur beyond the one layer primary follicle stage. Studies have also validated the existence of an intraovarian interleukin-1 system t hat may act as a mediator of luteinizing hormone stimulated periovulatory e vents. A host of other factors are actively being investigated. Further res earch will be needed to understand the in vivo significance of these findin gs to better determine which substances are of primary importance and which factors may supply only redundant functions.