Journal of Clinical Endocrinology & Metabolism, Vol 56, 1178-1187, Copyright © 1983 by Endocrine Society

ARTICLES

Studies of the human testis. XVIII. Simultaneous measurement of nine intratesticular steroids: evidence for reduced mitochondrial function in testis of elderly men

J Takahashi, Y Higashi, JA LaNasa, K Yoshida, SJ Winters, H Oshima and P Troen

To determine the basis for the decline in testosterone production by the aged testis, intratesticular unconjugated steroids, including testosterone, pregnenolone (3 beta-hydroxy-5-pregnen-20-one), 17 alpha- hydroxypregnenolone (3 beta,17 alpha-dihydroxy-5-pregnen-20-one), dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one), androstenediol (5-androstene-3 beta,17 beta-diol), progesterone, 17 alpha-hydroxyprogesterone, androstenedione (4-androstene-3,17-dione), and 17 beta-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 less than 0.05) in aged patients [3.3 +/- 1.9 ng/ml and 0.86 +/- 0.53 microgram/g tissue (mean +/- SD)] than in young men (6.4 +/- 1.9 ng/ml and 1.7 +/- 1.1 microgram/g tissue), while circulating LH levels were higher (P less than 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 delta 4 steroids, 17 alpha-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 less than 0.05) in aged patients (1.94 +/- 0.93 microgram/g tissue), than in young patients (3.68 +/- 1.90 micrograms/g tissue). The sum of the nine intratesticular steroids measured was positively correlated (P less than 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.

This article has been cited by other articles:

				ESHRE Capri Workshop Group Fertility and ageing Hum. Reprod. Update, May 1, 2005; 11(3): 261 - 276. [Abstract] [Full Text] [PDF]

				C. E. Fluck, W. L. Miller, and R. J. Auchus The 17, 20-Lyase Activity of Cytochrome P450c17 from Human Fetal Testis Favors the {Delta}5 Steroidogenic Pathway J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3762 - 3766. [Abstract] [Full Text] [PDF]

				A. M. Matsumoto Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2002; 57(2): M76 - 99. [Full Text]

				S. J. Winters, J. Takahashi, and P. Troen Secretion of Testosterone and Its {Delta}4 Precursor Steroids into Spermatic Vein Blood in Men with Varicocele-Associated Infertility J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 997 - 1001. [Abstract] [Full Text]