The effects of gonadotropin suppression and selective replacement on insulin-like factor 3 secretion in normal adult men

Context: Gonadotropic regulation of the testicular Leydig cell hormone insulin-like factor 3 (INSL3) is incompletely characterized. Objective: The objective of this study was to assess the effects of gonadotropin suppression and induced or spontaneous recovery on serum INSL3. Design and Participants: Serum samples from 15 men enrolled in a short-term study of gonadotropin stimulation, suppression, and recovery and 11 men in a long-term study of gonadotropin suppression and spontaneous recovery were analyzed for INSL3. Intervention: Gonadotropins were suppressed by exogenous testosterone and progestin. Recovery was spontaneous or induced with exogenous gonadotropins. Outcome Measure: The outcome measure was serum INSL3 in relation to other reproductive hormones. Results: Serum INSL3 was not acutely sensitive to gonadotropins. In both studies, INSL3 declined markedly with gonadotropin suppression (6-13.5% of baseline; P < 0.05). In the short-term study, human chorionic gonadotropin partially restored suppressed serum INSL3 within 4 d of administration (from 7.5 to 38.3% baseline; P < 0.05); the increase correlated with the corresponding increase in serum pro-alpha C (r = 0.82; P < 0.01). FSH did not stimulate the suppressed INSL3. In the long-term study, serum testosterone recovered significantly better (80% baseline) compared with serum INSL3 (38.9% baseline; P < 0.01) in the presence of fully recovered serum LH. Conclusions: INSL3 is not sensitive to gonadotropin stimulation in normal men, but declines markedly in response to gonadotropin deprivation. After suppression, INSL3 was responsive to hCG 4 d after administration. After long-term suppression, INSL3 did not recover to the same degree as testosterone, suggesting that INSL3 is more sensitive to Leydig cell impairment than testosterone.