The interplay of insulin-like growth factors, gonadotropins, and endocrine disruptors in ovarian follicular development and function.
Over the past 20 years, the expression, signaling mechanisms, and roles of members of the insulin-like growth factor (IGF) family (ligands, receptors, binding proteins, and binding protein proteases and their inhibitors) have been elucidated in ovarian follicle function in humans and other species. In vitro studies with human, nonhuman primate, and farm animal granulosa and thecal cells and genetic approaches using mouse knockout models for IGF family members have revealed that IGFs are key intraovarian regulators of follicle growth, selection, atresia, cellular differentiation, and steroidogenesis, oocyte maturation, and cumulus expansion. Some of these actions are synergistic with gonadotropins, although most are not sustainable with IGFs alone and require gonadotropin actions, thereby designating IGFs as "co-gonadotropins." In the human disorder of polycystic ovarian syndrome, characterized by small antral follicle arrest, the IGF system appears to contribute to the observed resistance to follicle-stimulating hormone action at the level of the granulosa compartment and the persistence of an androgen-dominant milieu in the arrested follicles. Interestingly, recent studies demonstrate that endocrine-disrupting chemicals can compromise IGF activity and signaling in the ovarian follicle, affecting follicle development, steroidogenesis, and oocyte quality. The successful development of a healthy oocyte and appropriate granulosa and theca cell steroidogenesis on a cyclic basis are contingent on multiple factors, including a properly functioning intraovarian IGF system. Disruption of even one component of this system can lead to abnormal follicular development and function and compromised reproductive capacity.
Kwintkiewicz
Jakub
J
Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, California 94143-0132, USA.
Giudice
Linda C
LC
D000818:Animals; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000494:pharmacology; D005260:Female; D006062:Gonadotropins / Q000502:physiology*; D006801:Humans; D051379:Mice; D023421:Models, Animal; D008954:Models, Biological; D006080:Ovarian Follicle / Q000187:drug effects* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013002:Somatomedins / Q000502:physiology*
D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D006062:Gonadotropins; D013002:Somatomedins