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Lack of a Direct Effect of Gonadotropin Hormone-Releasing Hormone Agonist on Human Testicular Steroidogenesis

Division of Urology, Department of Surgery, and Division of Endocrinology, Department of Medicine, UCLA School of Medicine, Harbor/UCLA Medical Center Torrance, California 90509

Address requests for reprints to: Jacob Rajfer, M.D., Harbor/UCLA Medical Center, Box 5,1000 West Carson Street, Torrance, California 90509.

In an attempt to determine whether the chronic administration of GnRH agonist (GnRH-A) has a direct inhibitory effect on testicular steroidogenesis in the human, the testes of four men with disseminated prostatic cancer who were treated with GnRH-A daily for at least 1 yr were assayed for intrates-ticular pregnenolone (5-pregnen-3β-ol-20-one), progesterone, dehydroepiandrosterone, 17-hydroxypregnenolone (5-pregnen-3β17-diol-20-one), 17-hydroxyprogesterone, androstenedione, and testosterone (T). In addition, testicular 17-hydroxylase, 17,20-desmolase, and 17β-hydroxysteroid dehydrogenase enzyme activites of the ⁴ pathway were measured. These intra-testicular steroids and enzyme activities from four GnRH-A-treated patients were compared to those in five men (controls) who were orchiectomized as the primary treatment for their disseminated prostatic cancer and in three other men who were treated for 3–12 months with GnRH-A daily but received, in addition to the daily GnRH-A, 1000 IUhCG, im, every other day for 3 days immediately before their salvage orchiectomy, which was performed when their disease progressed. In the control group, the ⁵-steroids, particularly dehydroepiandrosterone and pregnenolone, represented the majority of the intratesticular steroids. Compared to control values, all intratesticular steroids except ⁴-P (for which there was no difference) were significantly lowered by treatment with GnRH-A. Intratesticular T was reduced by 98% from 328 ± 139 (±SEM) ng/g testis in the control group to 8 ± 3 in the GnRH-A-treated group (P < 0.01). The additional treatment with hCG for 3 days in the GnRH-A-treated group reversed the inhibition of all steroids to either control or above control levels, with intratesticular T rising to 1144 ± 273 ng/g testis. A similar trend was found for all three enzymatic activities, i.e., GnRH-A alone inhibited each of the enzymatic activities, whereas the addition of hCG reversed this inhibition by GnRH-A. These data indicate that the chronic administration of GnRH-A to elderly men results in inhibition in both the ⁴ and ⁵ pathways, with a subsequent decrease in the intratesticular T concentration. The ability of exogenous hCG to reverse both the reduction in ⁴ and ⁵ intratesticular steroid content and the intratesticular enzyme activities induced by GnRH-A treatment supports the concept that GnRH-A does not have a direct inhibitory effect on testicular T biosynthesis.

Received March 7, 1985.

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