Resensitization of Testosterone Production in Men after Human Chorionic Gonadotropin-Induced Desensitization*

In rats, monkeys, and man, 24−h exposure to hCG can lead to a loss of testicular LH receptors and/or a decrease in the ability of the testis to produce testosterone inresponse to LH (desensitization). Such desensitization seems to be related to a block in the conversion of 17−hydroxyprogesterone to testosterone. In man, this desensitization is reflected by a plateau in serum testosterone (after a small early rise) for 4−24 h after hCG administration despite high serum hCG and rising serum 17−hydroxyprogesterone. After 72−h exposure to hCG, serum testosterone in men doubles, suggesting that the testis has regained sensitivity to gonadotropin (resensitization) with regard to testosterone production. To explore themechanism of this resensitization, we measured the acute (2−4 h) changes in serum levels of testosterone or testosterone precursor steroids in young men after im injection of hCG in both the basal and the resensitized state (72−h exposure to hCG) as indicators of the ability of the testis to produce testosterone or testosterone precursor steroids at those times. The acutehCG-induced rises in serum testosterone were the samein the resensitized and basal states [649 ° 215 vs. 637 ° 131 (SE) area units], confirming the resensitization of testosterone production. The acute hCG−induced rises in the A′ precursors of testosterone, 17−hydroxyprogesterone, and androstenedione, which were significant in the basal state(427 ° 54 and 156 ° 27 area units, respectively; P < 0.001), were abolished in the resensitized state (59 ° 50 and 43 ° 42 area units; P x0030; NS). In contrast, the acute hCG−induced rise in the A5 steroid dehydroepiandrosterone, which was not significant in the basal state (182 ° 136 area units; P 0 NS), was significant in the resensitized state (333 °113 area units; P < 0.01). Ten days after a single injection of hCG,serum testosterone was reduced below basal (419 ° 52 vs. 575 ° 91 ng/dl;P < 0.05), while the acute hCG−stimulated rise in serum 17−hydroxyprogesterone was greater than basal (1302 ° 262 vs. 640 ° 123 area units; P < 0.02), suggesting prolonged persistence of the block in conversion of 17−hydroxyprogesterone to testosterone. FSH administration for 72 h did not affect the responses to hCG. We conclude that resensitization of testosterone production after 72 h of hCG exposure is associated with the loss of acutely hCGreleaseable 17−hydroxyprogesterone and androstenedione, while acutely releaseable dehydroepiandrosterone is not reduced. These findings are consistent with a shift in the pattern of testosterone biosynthesis from the A4 to the A5 pathway, depletion of acutely releaseableintracellular pools of A4 steroids without a shift to the A5 pathway, an enzymatic block in the conversion of A5 to A′ steroids, or some combination of these mechanisms.