Effects of insulin-like growth factor 1 (IGF-1) on early folliculogenesis in polycystic ovaries from ovulatory and anovulatory women
Sharron A Stubbs, Kate Hardy & Stephen Franks
Preantral follicle development in polycystic ovaries (PCO) is characterised by an increased proportion of early growing follicles. We have previously shown that IGF-1 stimulates initiation of follicle growth in normal and PCO (Endocrine Abstracts 2004 7 P172). Here we have extended these studies, specifically to examine whether the ovulatory status of the patients from whom tissue is obtained influences the response to IGF-1. Small ovarian biopsies were obtained (with ethical committee approval and informed consent) from patients undergoing routine laparoscopy. Tissue was obtained from 33 women with normal ovaries and regular cycles, 11 women with PCO and regular cycles (ovPCO) and 10 women with PCO and anovulatory cycles or amenorrhea (anovPCO). Tissue was divided into pieces less than 1 mm3 and cultured for 7 days on growth factor-reduced Matrigel coated inserts in the presence or absence of IGF-1 (0.1100 ng/ml). A total of 503 follicles were analysed. As expected, in the absence of IGF a higher proportion of follicles had initiated growth in PCO compared with normal tissue (normal 51%, ovPCO 74%, anovPCO 75%, Chi-square 11.5, P=0.0031). IGF-1 produced a maximal response at a dose of 1 ng/ml in each ovarian type. The proportion of follicles initiating growth in response to 1 ng/ml IGF-1 was 96% in normal tissue (P<0.0001 compared with no IGF; Fishers exact test), 91% in ovPCO (P=0.0258) and 92% in anovPCO (P=0.08). In summary, IGF-1 stimulates initiation of follicle growth in normal ovaries but to a much lesser extent in both ovPCO and anovPCO (in which the percentage of growing follicles is already much higher than normal in the absence of added IGF). These data raise the possibility of increased endogenous IGF tone as a contributing factor to abnormal folliculogenesis in PCO.