In Vitro and in Vivo Studies on Leydig Cell Function in Old Rats

Abstract

Young adult (3 months old) and old (26\p=n-\28 months old) male Wistar rats were studied. Testicular weight was 1.66 g (range: 1.33 \p=n-\ 2.86) in the younger group and 1.62 g (range: 1.04 \p=n-\ 1.90) in the older group. The total Leydig cell volume as measured by a quantitative histometric method was significantly larger in the old animals (\l =x_\ = 0.153 ml vs. \l=x_\ = 0.089 ml). The testicular HCG binding capacity was 2.54 ng HCG per 100 mg tissue (range: 1.88 \p=n-\3.77) in the younger animals and 1.83 ng HCG per 100 mg tissue (range: 0.80 \ p=n-\ 3.02) in the older ones (P < 0.01). Plasma testosterone was on an average 242 ng/100 ml (range: 72 \ p=n-\1162) in the young adult rats and 91 ng/100 ml (range: 23 \p=n-\277) in the older rats. Plasma LH was only slightly (P < 0.05) decreased and was 49 ng LH\p=n-\RP\p=n-\1/ml(range: 14 \p=n-\ 120) in the younger group and 40 ng LH\p=n-\ RP\p=n-\1ng/ml (range: 5 \ p=n-\ 98) in the older.

Impact of Aging on Steroid Hormone Biosynthesis and Secretion

“…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.…”

“…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].…”

“…When specifically challenged in vitro, isolated Leydig cells of older rats of several different strains show significantly less steroidogenic response to tropic hormone stimulation than do cells from young animals [162,175,178,[181][182][183]. 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].…”

“…The rat is the most popular laboratory animal to examine the effects of aging on testicular androgen synthesis and secretion. A number of studies carried out during the past few decades have led to a clear demonstration that aging leads to significant reduction in blood testosterone levels in several rat strains [157][158][159][160][161][162][163][164][165][166][167][168][169].…”

“…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].…”