Autocrine/Paracrine Regulation of the Ovarian Follicle

Classically, the pituitary gonadotropins (i.e., follicle-stimulating hormone and luteinizing hormone) and gonadal steroids (primarily estrogen) have been assigned the role of primary regulators of the ovarian life cycle. As the complexities of the process of follicular growth, maturation and ovulation are elucidated, the inadequacies of this hypothesis have become evident. To better explain observed phenomena such as recruitment and selection of the dominant follicle, a system of intraovarian regulators has been proposed that would work in concert with gonadotropins and steroids amplifying, attenuating or even mediating gonadotropin action. These locally produced factors are thought to function mainly through one of two pathways. In the paracrine pathway, regulators diffuse locally from producer cells to distinct target cells within the same organ. In the autocrine pathway, the regulator acts via surface receptors at its cell of origin. The list of putative autocrine/ paracrine regulators in the ovary is growing rapidly. To prioritize the potential physiological relevance of these factors, it has been suggested that to qualify as a bona fide intraovarian regulator, a candidate should show evidence of local production, reception, action and some degree of indispensability to the process of follicular development and ovulation. Autocrine/ paracrine regulators currently under study include the insulin-like growth factor system, which appears to function as an amplifier of gonadotropin hormonal action. Also, there is the transforming growth factor-β gene superfamily, which includes activin, inhibin and growth and differentiation factor-9. Data suggest that activin and inhibin work in concert as attenuators or amplifiers of gonadotropin action, and that growth differentiation 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 that may act as a mediator of luteinizing hormone stimulated periovulatory events. A host of other factors are actively being investigated. Further research will be needed to understand the in vivo significance of these findings to better determine which substances are of primary importance and which factors may supply only redundant functions.