Insulin-Like Factor 3: a new circulating marker for the polycystic ovary syndrome-type of ovarian dysfunction
R Pasquali, L Patton, A Vaccina, R De Iasio, U Pagotto & A Gambineri
Insulin-like factor 3 (INSL3), a member of the relaxin-insulin family, is produced in the Leydig cells and at reduced levels in ovarian thecal cells. As ovaries from most of PCOS are characterized by an hyperplasia of the theca interna, we hypothesized that INSL3 could be overproduced in PCOS women and therefore that circulating levels of this hormone could became a new marker for the syndrome. Forty lean and obese women with PCOS and 20 controls comparable for age and weight were enrolled. Basal blood samples for androgens, SHBG, estradiol, LH, FSH, glucose and insulin determinations were collected. All participants underwent also an oral glucose tolerance test, whereas PCOS women only performed also an ACTH1-24 test (250 μg ACTH1-24 i.v. with blood taken at 0 and 60 min) and a GnRH agonist test (100 μg GnRH agonist s.c. with blood taken at 0 and 24 h) after 4 days of treatment with dexamethasone (2 mg orally daily) to suppress adrenal androgen production. INSL3 serum concentrations were measured by a radioimmunoassay method. We found that INSL3 concentration was: i) significantly higher in PCOS patients respect to controls (226.0±89.2 vs. 164.5± 43.6 pg/ml, P=0.005); ii) positively correlated with total (r=0.431, P< 0.001) and free testosterone (r=0.251, P=0.043), androstenedione (r=0.260, P=0.035) and 17OH-progesterone (r=0.246, P=0.049) levels in the entire population; and iii) positively correlated with suppression of free testosterone by dexamethasone (r=0.459, P=0.005) and with the responsiveness of androstenedione (r=0.453, P=0.003) and 17OH-progesterone (r=0.490, P=0.001) to GnRH agonist (markers of ovarian androgen function) in PCOS. These data strongly suggest that INSL3 could be used as a new circulating marker for the PCOS-type of ovarian dysfunction.