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

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Abstract
In rats, monkeys and man, 24 h exposure to hCG [human chorionic gonodotropin] can lead to a loss of testicular LH [lutropin] receptors and/or a decrease in the ability of the testis to produce testosterone in response 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; this suggests that the testis has regained sensitivity to gonadotropin (resensitization) with regard to testosterone production. To explore the mechanism of this resensitization, the acute (2-4 H) changes in serum levels of testosterone or testosterone precursor steroids in young men were measured after i.m. injection of hCG in both the basal and the resensitized state (72 h exposure to hCG), thus indicating the ability of the testis to produce testosterone or testosterone precursor steroids at those times. The acute hCG-induced rises in serum testosterone were the same in 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 .DELTA.4 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 = NS [not significant]). In contrast, the acute hCG-induced rise in the .DELTA.5 steroid dehydroepiandrosterone, which was not significant in the basal state (182 .+-. 136 area units; P = 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); this suggesting prolonged persistence of the block in conversion of 17-hydroxyprogesterone to testosterone. FSH [follitropin] administration for 72 h did not affect the responses to hCG. Resensitization of testosterone production after 72 h of hCG exposure is apparently associated with the loss of acutely hCG-releaseable 17-hydroxyprogesterone and androstenedione; acutely releaseable dehydroepiandrosterone is not reduced. These findings are consistent with a shift in the pattern of testosterone biosynthesis from the .DELTA.4 to the .DELTA.5 pathway, depletion of acutely releasable intracellular pools of .DELTA.4 steroids without a shift to the .DELTA.5 pathway, an enzymatic block in the conversion of .DELTA.5 to .DELTA.4 steroids, or some combination of these mechanisms.