The Androgen Status of Aging Male Rats*

Abstract

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)

Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

“…Finally, it may also be hypothesized that gonadal hormones are important in the initial phases of thymic regression, while later accumulating age-related functional or structural defects (37) are responsible for the maintenance/progression of thymic involution. In agreement with this hypothesis are data showing that: i) normal, agerelated androgen depletion (38) exerts no beneficial effect on the aged thymus (39), and ii) castration of old rats does not restore thymic weight to the level found in young animals (40).…”

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

“…Likewise, aged Leydig cells from Brown Norway rats also exhibited a significant reduction in gonadotropin (LH) receptor content [187]. Contrary to these findings, other investigators failed to observe any reduction in gonadotropin binding either in vivo [162] or in vitro [177,185,188]. In addition, gonadotropin stimulation of cAMP production and PKA activity in Leydig cells was unaffected by the aging process [182,183,186].…”

“…Tsitouras et al, [184] reported that in vivo pretreatment with, but not in vitro exposure to, hCG reverses the testosterone secretory defect of Leydig cells from old rats. Overall, these changes appear not to be a function of gonadotropin receptor activity, or cAMP formation [162,177,182,183,185,186] or a defect in the steroid hormone synthesizing enzymes [176,186] although there are some exceptions to this. For example, Pirke et al, [162] reported significant loss of hCG binding to whole testicular membranes of old rats, while Tsitouras et al, [182] observed only a modest decrease in hCG binding to membrane preparations from the purified Leydig cells.…”

“…Only studies conducted by Kaler and Neaves [177] reported no significant differences in testosterone production by isolated Leydig cells from old rats as compared to similarly isolated cells from young controls [177]. Tsitouras et al, [184] reported that in vivo pretreatment with, but not in vitro exposure to, hCG reverses the testosterone secretory defect of Leydig cells from old rats.…”

“…A number of studies indicate that the number of Leydig cells per testis is either unchanged or increased [162,[176][177][178]. In contrast, occurrence of Leydig cell hyperplasia as a consequence of aging has also been reported in stallions [179] and humans [141].…”