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Recombinant Human Follicle-Stimulating Hormone Administration Increases Testosterone Production in Men, Possibly by a Sertoli Cell-Secreted Nonsteroid Factor

División Endocrinología, Hospital Carlos G. Durand (O.L., S.A., C.T., C.A.), and Laboratorio de Estudios Hormonales (C.Z.), Buenos Aires; and Instituto de Analisis Biologicos Endocrinologies (D.A., M.C., H.S.), La Plata, Argentina

Address all correspondence and requests for reprints to: Dr. Oscar A. Levalle, División Endocrinología, Hospital Carlos G. Durand, Díaz Velez 5044, 1405 Buenos Aires, Argentina.

We previously showed that recombinant human FSH (R-FSH) in males increased the testosterone (T) concentration in spermatic venous blood (SB). To investigate the effect of R-FSH on spermatic steroid levels and the action of steroid- and LH-free SB on isolated Leydig cells, nine normospermic males were studied during spermatic cord surgery. Peripheral blood and SB samples were collected before and 30 min after iv administration of 150 U R-FSH to measure LH, FSH, T, estradiol, 17-hydroxyprogesterone, and sex hormone-binding globulin, and in SB, androstenedione (⁴) and dehydroepiandrosterone (DHEA) were also measured. LH bioactivity was assessed by in vitro production of T in isolated Leydig cells. The actions of R-FSH and SB (steroid and LH free) were analyzed in the bioassay. Data are expressed as the mean ± SE.

FSH in peripheral blood and SB increased by 411% and 477% after R-FSH administration. R-FSH induced a significant increase in spermatic T (basal vs. 30 min, 326.4 ± 98.5 vs. 732.4 ± 152.8 ng/mL; P < 0.047) and in spermatic estradiol (289.5 ± 66.9 vs. 535.6 ± 83.4 pg/mL; P < 0.036). The T/⁴ ratio (36.9 ± 9.2 vs. 74.5 ± 13.3; P < 0.019) and the T/DHEA ratio (10.8 ± 1.1 vs. 22.4 ± 4.9; P < 0.024) increased significantly. In isolated Leydig cells, R-FSH did not change T production, but the SB (steroid and LH free) after R-FSH administration induced an increase in T production (3.3 ± 0.6 vs. 4.9 ± 0.6 ng/tube; P < 0.04). LH-like activity was found in a more than 50,000-Da fraction after centrifugation in Amicon filters, even in the presence of anti-LH.

These results suggest that R-FSH increases the production of T by Leydig cells through a Sertoli cell-released nonsteroid factor with a molecular mass greater than 50 kDa. The increase in the T/⁴ and T/DHEA ratios indicates that this factor would act by amplifying the LH response through the ⁵ pathway and the 17ß-hydroxysteroid dehydrogenase enzyme.

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