Kathleen C. Chambers

Age-related deficits in brain androgen binding and metabolism, testosterone, and sexual behavior of male rats

Brain androgen binding and metabolism, serum testosterone (T), and sexual behavior were measured in old and young male Fischer 344 rats. After completion of sexual behavior tests, blood was collected for T assay and brains were removed for simultaneous measurements of cytosolic (ARc) and nuclear (ARn) androgen receptors and aromatase activity (AA) in the preoptic area (POA), hypothalamus (HYP) and amygdala (AMG). In Experiment 1, old and young intact males were examined. None of the old males ejaculated in any of the tests of sexual behavior whereas all of the young males ejaculated. The old males had lower levels of serum T, lower levels of ARn in the POA and HYP and lower levels of AA in the POA. The ARc levels of the old and young males did not differ. Experiment 2 was designed to determine if the deficits in brain androgen binding and metabolism were due to low levels of T. Old and young T-treated gonadectomized (GX-T) males and young intact (I) males were examined. T levels were comparable in the young and old GX-T males and were higher in each of these groups than in the young I males. In sexual behavior tests, all of the young but only 25% of the old GX-T males ejaculated. Although ARn levels in the old GX-T males were lower than in the young GX-T males, they were comparable to the young I male levels. No age-related differences in T induction of AA were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Sexual behavior in old male rhesus monkeys: Influence of familiarity and age of female partners

Old male rhesus monkeys (Macaca mulatta)whose sexual behavior had declined over a 10-year period were studied. The same ovariectomized females, comparable in age to the males (about 20 years old), served as sexual partners during the 10 years. In the first experiment the old males were paired with unfamiliar females to determine whether changing sexual partners would reverse the decline in performance that had been observed. The unfamiliar females, also about the same age as the males, were ovariectomized and treated with estradiol before pairing, as were the familiar females. Although the males contacted the unfamiliar females more often than they contacted the familiar females, there were no other differences in sexual activity. The two groups of females did not differ in their behavior toward the males. The low level of sexual performance by the males with both familiar and unfamiliar females could have been the result of decreased sexual initiative and responsiveness associated with the advanced age of the females, so a second experiment was undertaken to test this possibility. The old males were paired with two different groups of unfamiliar, intact, cycling females. One group was young (about 4 years old), the other old (about 20 years). The sexual responses of the males to both young and old females were the same. The two groups of females did not differ in their behavior toward the males.

Testosterone and the decline of sexual behavior in aging male rats

This experiment was designed to elucidate the role of testosterone in the decline of sexual behavior in aging males. Old (25 months) and middle-aged (10 months) male rats were given six tests (30-min long) of sexual behavior. The old males then were divided into two groups: intact and castrated with testosterone treatment. The middle-aged males were divided into three groups: intact, castrated with testosterone present all the time, and castrated with testosterone present only when tested. The old males were given another set of six tests 1 week after the operation (when 27.5 months old), and the middle-aged males were given three more sets of six tests 8, 26, and 39 weeks after the operation (when 15, 19, and 22.5 months old, respectively). Blood drawn after each test set was assayed for testosterone. The middle-aged intact males had higher levels of testosterone than the old intact males, and the testosterone-treated castrated males, whether middle-aged or old, had higher levels than the intact males. The presence of higher levels at the time of testing resulted in increased rates of mounting and intromitting in old males and an attenuated decline in the mount rate and percentage of tests with intromissions in middle-aged males. The middle-aged castrated males with continuous testosterone differed from the middle-aged castrated males with periodic testosterone only in the mount-intromission interval; the former group had a longer interval. It was concluded that testosterone, in general, does not prevent or reverse the decline in sexual performance of aging male rats and that the degree and rate of decline do not depend on whether or not testosterone is continuously present.

Sexually dimorphic acquisition of a conditioned taste aversion in rats: Effects of gonadectomy, testosterone replacement and water deprivation

Abstract Sexual dimorphism was found to exist with respect to the acquisition of a conditioned taste aversion. When 0.30 meq of LiCl was used as a toxin, the proportion of male rats in whom aversion developed was greater than the proportion of females. Gonadectomy had an unclear effect on the behavior of females. However, gonadectomized males had less of a tendency to acquire the aversion than did intact males. Testosterone replacement counteracted this effect. Water deprivation, which has been shown to feminize testosterone-dependent slow extinction of a conditioned taste aversion, reduced the proportion of males in whom aversion developed. Thus, sexual dimorphism in the acquisition of this behavior depends at least in part on the presence of testosterone.

Diurnal patterns of testosterone, dihydrotestosterone, estradiol, and cortisol in serum of rhesus males: relationship to sexual behavior in aging males.

Abstract This study was carried out to determine differences between old and young rhesus males in levels and diurnal patterns of testosterone, dihydrotestosterone, cortisol, and estradiol, and to determine correlations between these hormones and sexual behavior of the old males. Blood was drawn from old (n = 9) and young (n = 9) rhesus males over 5 consecutive days at 0900, 1300, and 2100 hr. The two groups of males did not differ in mean serum levels of testosterone, dihydrotestosterone, or estradiol at any time. Although the old and young did not differ in cortisol levels at 0900 and 1300 hr, the cortisol levels at 2100 hr were lower in the old males. Diurnal variations in testosterone, dihydrotestosterone, and cortisol were comparable in old and young males. Mean serum levels of estradiol were significantly higher at 0900 hr than at 1300 hr in the old males, whereas in the young males estradiol levels did not differ with time of day. There was a significant positive correlation between testosterone and yawning rate, and cortisol levels were correlated positively with rate of contacting, rate of mounting, and percentage of tests with erections. The decline in sexual performance of old rhesus males cannot be attributed to changes in the levels or diurnal patterns of testosterone, dihydrotestosterone, or estradiol, but lower cortisol levels in old males may contribute to the decline in sexual behavior.

Age-Related Deficits in Brain Estrogen Receptors and Sexual Behavior of Male Rats

Neural estrogen receptors (ER), serum testosterone (T), estradiol (E2) and luteinizing hormone (LH), and masculine sexual behavior were measured in young (5 months) and old (24 1/2 months) Fischer 344 male rats. We found that old intact males, which displayed significantly lower levels of sexual behavior, T, and LH than young intact males, also had lower levels of nuclear ER (ERn) in the amygdala (AMG). The age difference in ER binding did not appear to be a consequence of altered blood E2 levels because circulating E2 did not differ between the two age groups. Gonadectomy eliminated ejaculatory behavior and significantly reduced ERn in young males. When we administered exogenous T to gonadectomized males in doses that approximated levels found in young intact males, we found that sexual performance of old males was stimulated to precastration levels but not to levels found in young males. Moreover, such treatment failed to increase ERn in the AMG of old males to the levels measured in the AMG of young males. These results suggest that there is an association between the inability of T to increase ERn concentration in the AMG and the deficits in sexual performance that are characteristic of old males. Thus, the capacity of neural tissue to bind estrogen, presumably derived from circulating T, may be a limiting factor in the determination of androgen responsiveness in aging males.

RELATIONSHIP OF FREE AND BOUND TESTOSTERONE TO SEXUAL BEHAVIOR IN OLD RHESUS MALES

Abstract Total serum testosterone concentrations, percentage of total serum testosterone bound to testosterone-binding globulin (TeBG), and estimates of free testosterone concentrations were determined in old and young male rhesus macaques. Also the sexual performance of the old (20 years and older) males was studied. The two groups did not differ in either the mean level of total testosterone or the index of free testosterone but the old males had a significantly higher percentage of testosterone bound to TeBG than did the young (10 years old) ones. We found significant negative correlations between the percentage of testosterone binding and sexual behavior in the old males. The percentage of bound testosterone was negatively correlated with the rates of contacting females, mounting, and intromission, and with the percentages of tests during which intromission and ejaculation occurred. Neither the total serum testosterone level nor the index of free testosterone correlated with the level of sexual performance.

Correlation of diurnal changes in hormones with sexual behavior and age in male rhesus macaques

We designed this study to determine whether the sexual behavior of male monkeys changes on a diurnal schedule that coincides with changes in the levels of hormones such as luteinizing hormone (LH), testosterone, estradiol, and cortisol, and whether these differences vary with age. Old (n = 8) and young (n = 8) males were bled and given sexual behavior tests eight times at 0900 and eight times at 2100. The old and young males did not differ in mean serum levels of testosterone, estradiol, cortisol, or LH. Testosterone and LH levels were lower at 0900 than at 2100 (p less than 0.01), and estradiol and cortisol levels were higher at 0900 than at 2100 (p less than 0.01). The young males had higher percentages of tests with erections, mounts, intromissions, and ejaculations than the old males (p less than 0.01). The rates of contacting, mounting, and intromitting were higher at 0900 than at 2100 (p less than 0.05). We failed to confirm previously obtained correlations between hormone levels and sexual performance, This failure led us to conclude that any significant correlation between sexual behavior and hormone levels must be regarded as tentative unless repeated in successive independent studies.

Sex Differences in Male-Typical Copulatory Behaviors in Response to Androgen and Estrogen Treatment in Rats

The present experiment was performed to test the hypothesis that gender differences in the capacity for brain estrogen synthesis could constitute a sexually dimorphic mechanism that limits the activational effects of testosterone (T) in females, and enhances them in males. We determined the effects of treatments with equivalent levels of either T or estradiol (E2) on olfactory behavior and mounting in age-matched heterosexually naive gonadectomized male and female rats that were genitally ansthetized with lidocaine paste in order to minimize the contribution of sexually dimorphic somatosensory inputs to the expression of copulatory behavior. We found that T stimulated mounting to a greater extent in males than in females, but had equivalent effects on mount latency and genital investigation in the two sexes. On the other hand, E2 stimulated equivalent levels of mounting in males and females and reduced mount latency to a similar extent in males and females. However, E2 had a pronounced effect on the levels of genital investigation in males but not in females. Serum steroid levels and the levels of nuclear steroid receptor occupation in the brain were not different between males and females, suggesting that the behavioral differences between males and females cannot be attributed to differences in peripheral steroid metabolism or brain uptake. The results obtained corroborate previous studies suggesting that female rats normally undergo considerable male-typical behavioral masculinization during fetal development. However, such male-typical features of normal development in female rats do not extend to the regulation of preoptic aromatase activity or to the capacity of females to display olfactory behaviors in response to adult E2 exposure, functions which are sexually dimorphic even in the rat. The present results support the view that gender differences in the capacity for brain estrogen synthesis contribute to the sexually dimorphic display of T-stimulated male-typical sexual motivation and copulatory behavior in rats.

Estradiol Accelerates Extinction of a Conditioned Taste Aversion in Female and Male Rats

Exogenous testosterone treatment prolongs extinction of conditioned taste aversions and estradiol treatment prevents testosterone from prolonging extinction in both gonadectomized males and females. Estradiol could require the presence of testosterone for its effect or its action alone could accelerate extinction. The first series of experiments were designed to test the hypothesis that estradiol accelerates extinction when it is given in the absence of testosterone. The results showed that estradiol accelerates extinction of conditioned taste aversions in the absence of testosterone in gonadectomized Sprague-Dawley females and Fischer 344 females and males. The second series of experiments were designed to determine whether estradiol and testosterone differ in the temporal requirements for their opposite effects on extinction. The results showed that estradiol can accelerate extinction when it is present before and during acquisition (from 8 days before until 3 days after acquisition) or when it is present before and during extinction (from 2 days after acquisition, which was 23 days before extinction, until extinction trials were terminated). This is in contrast to a previous finding that testosterone prolongs extinction only when it is present before and during extinction. The following two hypotheses were suggested to account for the temporal effects of estradiol on extinction of conditioned taste aversions: (1) the presence of estradiol during acquisition reduces the effectiveness of LiCl through its action on the opioid system, and the presence of estradiol during extinction activates a neural pathway, such as that associated with activity levels, that accelerates extinction of passive avoidance tasks in general or (2) the presence of estradiol before, not during, acquisition or extinction accelerates extinction because of its illness-inducing properties. Most of the evidence supports the second hypothesis.