Early origins of polycystic ovary syndrome.
The prenatally androgenised female rhesus monkey has become a model for polycystic ovary syndrome (PCOS) in women, with early prenatal androgenisation entraining a permanent PCOS-like phenotype characterised by luteinising hormone (LH) hypersecretion due to reduced hypothalamic sensitivity to steroid negative feedback and relative insulin excess associated with increased abdominal adiposity. These combined reproductive and metabolic abnormalities occur in combination with ovarian hyperandrogenism and follicular arrest in adulthood, and with premature follicle differentiation and impaired embryo development during gonadotrophin therapy for in vitro fertilization (IVF). The ability of prenatal androgen excess in fetal rhesus monkeys to entrain multiple organ systems in utero provides evidence that the hormonal environment of intrauterine life programmes target tissue differentiation, raising the possibility that hyperandrogenism in human fetal development promotes PCOS in adulthood. This hypothesis developed in prenatally androgenised female rhesus monkeys, however, also must include data from clinical studies of PCOS to clarify the homology between human and non-human primates in intrafollicular steroidogenesis and its impact on oocyte developmental competency. By doing so, future studies promise to develop new clinical strategies that will lead to improved pregnancy outcome and reduced pregnancy loss in women with disorders of insulin action, including PCOS, obesity and diabetes mellitus.
Dumesic
Daniel A
DA
Wisconsin National Primate Research Center, University of Wisconsin, Madison, 53715, USA. danieldumesic@aol.com
Schramm
R Dee
RD
Abbott
David H
DH
D000818:Animals; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D006062:Gonadotropins / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008253:Macaca mulatta; D008954:Models, Biological; D009865:Oocytes / Q000502:physiology*; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000209:etiology* / Q000378:metabolism; D013045:Species Specificity; D014770:Virilism / Q000378:metabolism*
D012739:Gonadal Steroid Hormones; D006062:Gonadotropins; D007986:Luteinizing Hormone