Insulin-Like Factor 3: A New Circulating Hormone Related to Luteinizing Hormone-Dependent Ovarian Hyperandrogenism in the Polycystic Ovary Syndrome

Abstract

Insulin-like factor 3 (INSL3), a circulating peptide hormone and a member of the relaxin-insulin family, is produced in the testicular Leydig cells and, to a lesser extent, in ovarian theca interna cells of antral follicles, the corpora lutea, and the ovarian stroma. Recent studies in rats suggest an important role for luteinizing hormone (LH) in stimulating gonadal expression of INSL3. Most women with polycystic ovary syndrome (PCOS) have a hyperplastic theca intema and cortical stroma and an increased number of small antral follicles. A majority-specially non-obese patients-have elevated circulating LH levels. This study estimated circulating levels of INSL3 by radioimmunoassay in 22 women with PCOS and normal body weight and 22 others who were overweight (body mass index [BMI] of 25-30 kg/m 2 ) or obese (BMI exceeding 30 kg/m 2 ). Each was matched for age and body weight with a non-PCOS control subject. Compared with control women, those with PCOS had greater insulin responses to oral glucose, higher androgen levels, and less frequent menstruation. Differences in androgen levels were most evident in normal-weight subjects, while differences in insulin responses to glucose were more evident in overweight/obese women. Baseline LH levels were highest in PCOS women of normal body weight. Serum levels of INSL3 were significantly higher in PCOS women than in control subjects, but only in those of normal body weight. In all women, serum INSL3 correlated positively with levels of total and free testosterone and with LH levels. In women with PCOS, concentrations of INSL3 were associated with greater responses of 170H-progesterone to buserelin, an index of ovarian hyperandrogenism. Levels of INSL3 also correlated positively with the number of ovarian follicles in women with PCOS. In contrast, women with PCOS exhibited no significant correlation between baseline LH levels and the number of follicles. These findings could be interpreted to mean that INSL3 is a circulating hormone related to LH-dependent ovarian hyperandrogenism in women with PCOS and normal body weight.