Context: Insulin-like factor 3 (INSL3), a member of the relaxin-insulin family, is produced in the Leydig cells and at reduced levels in ovarian theca interna cells of antra follicles as well as in the corpora lutea and ovarian stroma. Among the factors potentially involved in the stimulation of gonadal expression of INSL3, recent data obtained in rats show an important role of LH. Ovaries from most women affected by polycystic ovary syndrome (PCOS) are characterized by hyperplasia of the theca interna and of cortical stroma and by an increased number of small antral follicles, and the majority of women with PCOS, particularly normal-weight subjects, have LH levels that are above the normal range.

Objective: To investigate INSL3 circulating levels in both normal-weight and overweight-obese PCOS women, and the association of INSL3 with gonadotropin and androgenic pattern and with ovarian morphology.

Design: Controlled study.

Setting: Academic Hospital.

Participants: 44 PCOS patients (22 normal-weight and 22 overweight-obese) and 44 controls comparable for age and body weight.

Main outcome measures: INSL3 serum concentrations, measured by radioimmunoassay, in PCOS patients and controls, and their correlation with clinical and biochemical phenotype and with ovarian morphology.

Results: INSL3 serum concentrations were significantly higher in PCOS patients with respect to controls (P=0.003), particularly in normal-weight (P=0.001), but not in overweight-obese (P=0.312) PCOS patients. INSL3 serum concentrations were positively correlated with total- and free-testosterone and with LH levels in all women (total testosterone, P<0.001; free testosterone, P=0.001; LH, P=0.002) as well as in PCOS patients (total testosterone, P=0.024; free testosterone, P=0.045; LH, P=0.049). Moreover, in the PCOS group, INSL3 levels were related to a greater 17OH-progesterone response to buserelin (P=0.015), an index of ovarian hyperandrogenism. Finally, in PCOS women, INSL3 levels were positively correlated with ovarian follicle number (P= 0.028).

Conclusions: INSL3 could be considered a new circulating hormone related to LH-dependent ovarian hyperandrogenism, particularly in normal-weight PCOS women.