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Studies of the Human Testis. XVIII. Simultaneous Measurement of Nine Intratesticular Steroids: Evidence for Reduced Mitochondrial Function in Testis of Elderly Men^*

Department of Medicine, Montefiore Hospital, and the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; and the Department of Urology, Louisiana State University Medical Center, New Orleans, Louisiana 70112

Address requests for reprints to: Dr. Philip Troen, Montefiore Hospital, 3459 Fifth Avenue, Pittsburgh, Pennsylvania 15213.

To determine the basis for the decline in testosterone production by the aged testis, intratesticular unconjugated steroids, including testosterone, pregnenolone (3β-hydroxy-5-pregnen-20-one), 17-hydroxypregnenolone (3β,17-dihydroxy-5-pregnen-20-one), dehydroepiandrosterone (3β-hydroxy-5-androsten-17-one), androstenediol (5-androstene-3β,17β-diol), progesterone, 17-hydroxyprogesterone, androstenedione (4-androstene-3,17-dione), and 17β-estradiol, were measured by simultaneous RIAs in 32 previously untreated elderly men (aged 61–85 yr) undergoing orchiectomy as therapy for prostatic carcinoma and 20 young men (aged 25–35 yr) with oligospermia and varicocele. In vitro steroidogenesis using labeled pregnenolone as substrate was also investigated.

Serum and intratesticular testosterone levels were lower (P < 0.05) in aged patients [3.3 ± 1.9 ng/ml and 0.86 ± 0.53 µg/g tissue (mean ± SD)] than in young men (6.4 ± 1.9 ng/ml and 1.7 ±1.1 µg/g tissue), while circulating LH levels were higher (P < 0.05) in elderly men (151 ± 105 ng/ml) than in the young men (79 ± 33 ng/ml), indicating that a primary pathological process affects the senescent testis, producing a decline in testosterone production. Study of bioconversion of [³H]pregnenolone to ⁴ steroids, 17-hydroxysteroids, and C₁₉ steroids as well as analysis of the relative amounts of intratesticular steroids, as determined by RIA, revealed no apparent differences in the process of microsomal steroidogenesis in elderly compared to that in young men. The sum of the nine measured intratesticular steroid concentrations per g tissue wt was significantly lower (P < 0.05) in aged patients (1.94 ± 0.93 µg/g tissue), than in young patients (3.68 ± 1.90 µg/g tissue). The sum of the nine intratesticular steroids measured was positively correlated (P < 0.01) with circulating LH levels in both patient groups, and the slope of this regression line was 14-fold greater for young men than for elderly men. Since the total concentration of the nine measured steroids reflects the pregnenolone supplied by the mitochondria within Leydig cells, it appears that the decline in Leydig cell function in aged men is attributable to a reduced supply of mitochondrial steroid precursors rather than to an impairment in microsomal steroidogenesis. (J Clin Endocrinol Metab 56: 1178,1983)

^* A portion of these data was presented at the 6th Annual Meeting of the American Society of Andrology, New Orleans, Louisiana, 1981. This work was supported in part by USPHS Research Grant 5-R01- HD-11468.

Received August 30, 1982.

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