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.
In male Sprague-Dawley rats between 3-24 months of age, plasma concentrations of testosterone declined by more than 50% while concentrations of LH in plasma remained relatively constant. During the same interval, body weight rose almost 50%, suggesting that total circulating amounts of testosterone, assuming a proportional expansion of plasma volume, remained relatively constant with increasing age and that total LH in the circulation actually increased in older rats. This assumption was justified by demonstrating that blood plasma volume increased in proportion to body weight over the range of ages and weights represented by rats in this study. Plasma testosterone levels achieved after the injection of gonadotropin were significantly lower in the oldest rats, but when adjusted for increased plasma volume, total testosterone added to the circulation in response to injected gonadotropin did not diminish with age. Age-related change was not detected in testosterone secretion by decapsulated rat testes, either under control conditions or after the addition of gonadotropin to the incubation medium. The average volume of individual Leydig cells remained near young adult values with advancing age, while the total number of Leydig cells per testis rose slightly in the oldest rats. Hence, diminished androgen status in old rats could not be attributed to functional or numerical deficits in the Leydig cell population. Instead, low plasma testosterone levels may have resulted from two interrelated extratesticular phenomena, dilution of secreted hormone with the expanded volume of plasma in a significantly larger body mass, and failure of LH levels to rise sufficiently to stimulate additional testosterone secretion. (Endocrinology 108: 712, 1981)
Enhanced nocturnal release of GH is decreased with aging in man, a change that may implicate GH in a general decline in anabolic metabolism associated with aging. The aim of this study was to determine whether nonhuman primates experience an age-related reduction in plasma GH levels by comparing the 24-h patterns of GH secretion in unrestrained young and aged male rhesus monkeys. Six young (8 yr old) and six aged (22+ yr old) intact rhesus males were fitted with indwelling jugular catheters, cranial platforms, and stainless steel cable tethers. Catheters passed from a swivel device at the top of each cage through a wall to an adjoining room. On four occasions, 1.0-ml blood samples were obtained from each male every 20 min for 24 h for plasma GH RIA. Plasma GH data were analyzed by the PULSAR program to detect hormone peaks. Mean 24-h plasma GH was less (P less than 0.0005) in aged males [0.84 +/- 0.04 ng/ml (+/-SEM)] than in young males (1.37 +/- 0.09 ng/ml). Likewise, the amplitudes of GH pulses were less (P less than 0.001) in aged males than in young males. Although no circadian pattern of GH concentrations was apparent in either age group, young males displayed more (P less than 0.05) nocturnal GH pulses (5.73 +/- 0.41 pulses/12 h) than those occurring during lights-on (3.09 +/- 0.32 pulses/12 h). The numbers of GH pulses in aged males (4.00 +/- 0.63 pulses/12 h) were similar to those in young males during lights-on, but aged males showed fewer (P less than 0.05) nocturnal GH pulses (4.27 +/- 0.47 pulses/12 h) than did young males. The duration of GH pulses in aged males (53.6 +/- 5.0 min) was similar to that in young males (50.6 +/- 5.0 min) during lights-off. Young males showed an extended (P less than 0.001) GH pulse duration (88.8 +/- 8.8 min) during lights-on that was not evident in aged males (66.2 +/- 5.4 min). These data demonstrate that unrestrained young rhesus males experience an enhanced nocturnal release of GH in terms of pulse frequency, and as in humans, this enhanced nocturnal release of GH is diminished with age. In addition, rhesus males experience, as do humans, a reduction in circulating GH levels as a function of age.
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