RECOMBINANT HUMAN FOLLICLE-STIMULATING-HORMONE ADMINISTRATION INCREASES TESTOSTERONE PRODUCTION IN MEN, POSSIBLY BY A SERTOLI CELL-SECRETEDNONSTEROID FACTOR

We previously showed that recombinant human FSH (R-FSH) in males incre ased the testosterone (T) concentration in spermatic venous blood (SB) . To investigate the effect of R-FSH on spermatic steroid levels and t he action of steroid- and LH-free SE on isolated Leydig cells, nine no rmospermic males were studied during spermatic cord surgery. Periphera l blood and SE samples were collected before and 30 min after iv admin istration of 150 U R-FSH to measure LH, FSH, T, estradiol, 17 alpha-hy droxyprogesterone, and sex hormone-binding globulin, and in SE, andros tenedione (Delta(4)) and dehydroepiandrosterone (DHEA) were also measu red. LH bioactivity was assessed by in vitro production of T in isolat ed Leydig cells. The actions of R-FSH and SE (steroid and LH free) wer e analyzed in the bioassay. Data are expressed as the mean +/- se. FSH in peripheral blood and SE increased by 411% and 477% after R-FSH adm inistration. R-FSH induced a significant increase in spermatic T (basa l vs. 30 min, 326.4 +/- 98.5 us. 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/Delta(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) incr eased significantly. In isolated Leydig cells, R-FSH did not change T production, but the SE (steroid and LH free) after R-FSH administratio n 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 f raction after centrifugation in Amicon filters, even in the presence o f anti-LR. These results suggest that R-FSH increases the production o f T by Leydig cells through a Sertoli cell-released nonsteroid factor with a molecular mass greater than 50 kDa. The increase in the T Delta (4) and T/DHEA ratios indicates that this factor would act by amplifyi ng the LH response through the Delta(5) pathway and the 17 beta-hydrox ysteroid dehydrogenase enzyme.