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The Effects of Gonadotropin Suppression and Selective Replacement on Insulin-Like Factor 3 Secretion in Normal Adult Men

University Department of Growth and Reproduction, Rigshospitalet (K.B., A.-M.A.), DK-2100 Copenhagen, Denmark; and Prince Henry’s Institute of Medical Research and Department of Obstetrics and Gynecology, Monash University, Monash Medical Center (K.L.M., R.I.M.), Monash, Clayton, Victoria 3168, Australia

Address all correspondence and requests for reprints to: Dr. Katrine Bay, University Department of Growth and Reproduction, Rigshospitalet, GR 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: katrine.bay{at}rh.hosp.dk.

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-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.

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