Attrition of the human leydig cell population with advancing age

Abstract

Existing evidence suggests that the aging human male experiences a gradual decline in testosterone production, a phenomenon that should be reflected in the Leydig cell population of the testis. It has been proposed that Leydig cells diminish in number with increasing age, but conflicting claims characterize reports of this topic. We have reinvestigated this possibility by histometric analysis of perfused testes from 25 men ranging from 18 to 87 years of age. Average single Leydig cell volume (2,943 +/- 623 micrometer 3, X +/- S.D.) did not change significantly with increasing age (r = 0.24, P greater than 0.2), suggesting that surviving cells remain active. Total testis weight (43.5 +/- 13.9 g) also did not change with age (r = 0.04, P greater than 0.5). However, both total Leydig cell volume and the absolute number of Leydig cells per individual decreased significantly as functions of age (r = -0.71, P less than 0.002, and r = -0.61, P less than 0.005, respectively). Analysis of relationship between these two parameters indicates that the total volume of Leydig cell cytoplasm contained within the human testis is determined by the number of cells present. Our results show that a pair of young adult testes endowed with more than 700 million Leydig cells at 20 years of age may be expected to undergo an attrition rate of approximately 80 million cells per subsequent decade of life. Thus, Leydig cell attrition is an important correlate of declining androgen status in aging men.

Leydig cell transplantation restores androgen production in surgically castrated prepubertal rats

“…Further, although Leydig cell steroid production lapses after only a week of culture, Leydig cell transplantation of 10% of the testicular volume has been shown to adequately maintain virility in males [13]. As Leydig cells normally comprise 2% and 5%-12% of the testicular cell population in mature rodents [14] and humans [15], respectively, the potential clinical application of Leydig cell transplantation should be further investigated.…”

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

“…Sarjent and McDonald were the first to report significant reduction in Leydig cell number in autopsy samples of men with an age greater than 20 years [134]. Decreased Leydig cell numbers have also been reported by Tillenger [135], Frick [136], Harbitz [137] and Kaler and Neaves [138]. In contrast to these findings, Sniffen, [139], as well as Sokal [140] observed no loss of Leydig cells with age, while Kothari and Gupta [141] reported total Leydig cell mass to be increased in testes from their older men.…”

Efficient and Unbiased Tools for Quantitating Leydig and Sertoli Cells in the Testis From Testes Biopsies

“…The total Leydig and Sertoli cell numbers, estimated by use of stereological methods, differed from the results obtained from most previous studies. The estimated total Sertoli cell numbers have been reported to range from 390 to 3700x10 6 and the total Leydig cell number from 400 to 800x10 6 , calculated from twodimensional profile counting (Cortes et al, 1987;Paniagua et al, 1987;Kaler and Neaves, 1978;Neaves et al, 1985). These large ranges may be ascribed to the difficulties in interpretation of results obtained from assumption based designs as previously described (Mendis-Handagama and Ewing, 1990;Mendis-Handagama, 1992).…”