The effect of human chorionic gonadotropin on serum levels of testosterone, estradiol, and sexual behavior in young and old rhesus males

Sexual behavior and serum levels of testosterone (T) and estradiol (E) were examined in five young and six old rhesus males (Macaca mulatta) before and after the injection of 500 and 1000 IU of HCG. The serum levels of T and E increased in both young and old males after injection of either dose of HCG. Serum levels of T were significantly higher in young than in old males in the period following the last injection of 1000 IU of HCG. Old males had significantly higher levels of serum E during treatment with 1000 IU of HCG, but serum E levels in the two groups did not differ before or after treatment. Serum levels of T and E did not differ between the young and old males when injected with 500 IU of HCG. HCG had no effect on sexual performance and the differences in levels of sexual performance between the young and old males were not eliminated.     

Sexual performance of old and young male rhesus macaques following treatment with GnRH

GnRH has been reported to facilitate sexual performance in a number of species. To determine whether the same was true for rhesus monkeys we measured sexual behavior and serum levels of testosterone (T) and luteinizing hormone (LH) following control tests and after treatment with two doses of GnRH. In the first experiment, old intact (N = 11) and old T-implanted, castrated (N = 4) rhesus macaques were examined. Mean intromission rate of old intact males was significantly lower following treatment with 100 micrograms of GnRH than following control injections. Other measures of sexual behavior did not differ across treatments. There were no significant treatment effects among the old castrated males. The failure to facilitate sexual performance may have been due to the age of the males and not to the species under study. Thus, in a second experiment the effects of GnRH were examined in young rhesus males. Again, there was no facilitation of sexual performance. This cannot be accounted for by a failure of GnRH to produce a physiological response. For both old and young intact males serum levels of LH and T increased significantly after treatment with both doses of GnRH. LH but not T levels increased significantly in the T-implanted males.     

Sexual behavior in response to testosterone in old long-term-castrated rhesus males

The sexual behavior of 20-year-old long-term-castrated and intact male rhesus macaques (Macaca mulatta) was observed. In the first experiment we compared the sexual behavior of males tested in 1980 with their performance in 1970 (before castration and sham castration) and in 1971 (1 year after the operation). In 1971 and 1980, the castrated males were tested while under testosterone propionate treatment. The castrated and intact males did not differ in any measures of sexual behavior over the 10-year period, but both groups showed a decline in the percentage of tests with intromissions and ejaculations; a decline in the rates of contacting, mounting, and intromitting; and an increase in the latencies to contact, intromit, and ejaculate. In a second experiment, the sexual performances of old castrated and intact males were compared to those of young intact males (8 to 12 years). The intromission rate and the percentage of tests with intromissions were significantly greater in young males than in old intact males, but did not differ from values for old castrated males. The old castrated and old intact males did not differ from each other in these measures. Young males had a higher percentage of tests with ejaculation than either group of old males. We have concluded that old long-term-castrated rhesus males retain the potential to display sexual behavior at levels comparable to those observed in old intact males.     

Relationship of free and bound testosterone to sexual behavior in old rhesus males

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.     

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)     

Change of female partner and postejaculatory performance of young and old rhesus males

This study was undertaken to determine whether a change of female partner following ejaculation would reduce the postejaculatory interval (PEI). The male subjects were seven old (mean age 22.4 years) and five young (mean age 12.2 years) rhesus males (Macaca mulatta). The female subjects were four ovariectomized females rendered sexually receptive by treatment with estradiol benzoate. Introduction of a different female following ejaculation significantly reduced the PEI and latency to a second ejaculation in both young and old males. However, a different female did not reduce latencies to preejaculatory levels. The potential for enhanced sexual performance was retained in old rhesus males.     

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<0.01), and estradiol and cortisol levels were higher at 0900 than at 2100 (p<0.01). The young males had higher percentages of tests with erections, mounts, intromissions, and ejaculations than the old males (p<0.01). The rates contacting, mounting, and intromitting were higher at 0900 than at 2100 (p<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.     

Apomorphine, deprenyl, and yohimbine fail to increase sexual behavior in rhesus males

Various doses of apomorphine, deprenyl, and yohimbine were administered to old (20-26 years) rhesus males that had been sexually active when younger and to younger (6-17 years) males that were characteristically sexually sluggish. These neuropharmacological agents have been reported to increase sexual behavior in male rats. In Experiment 1, 10 old intact rhesus males were tested after injection of vehicle and apomorphine, and 6 old testosterone-treated castrated males were tested after treatment with deprenyl and yohimbine and the vehicles for each drug. In experiment 2, the 5 younger males were tested after treatment with each of the drugs and with the vehicles for each drug. There were a few minor changes in behavior associated with certain doses of each of the drugs and as many depressive as facilitative effects on sexual behavior. This suggests that there are basic differences between rats and rhesus macaques in the systems mediating sexual behavior.     

Sexual solicitation by middle-aged and old rhesus females

The sexual behavior of old and middle-aged ovariectomized estradiol treated females was studied in pair tests with old and middle-aged male rhesus macaques (Macaca mulatta). The ages of the subjects (females, N = 21 and males, N = 16) ranged from 9 to 26 years. We found no significant differences between old and middle-aged females in the overall rates of soliciting sexual behavior, and they solicited sexual behavior as readily from old as from middle-aged males. Old males were less active sexually than middle-aged males, but the two groups did not behave differently toward old and middle-aged females. Old and middle-aged females were equally proceptive toward old and middle-aged males and equally attractive to them. Because the ratio of female presents to male contacts did not differ between the old and middle-aged females, the two groups may be considered equally receptive as well. We found no evidence that the capacity to respond sexually to extradiol treatment is diminished in old rhesus females.     

Testosterone is more effective than dihydrotestosterone plus estradiol in activating sexual behavior in old male rats

Sexual behavior declines in old male rats, and testosterone therapy does not restore the behavior to levels found in young males. If as a result of aging, old males have less capacity to aromatize or reduce testosterone, dihydrotestosterone plus estradiol treatment should be more effective than testosterone treatment in restoring sexual behavior in old castrated males. In a test of this hypothesis, the sexual behavior of old (24 months) castrated Fischer 344 males given injections of testosterone propionate (TP) or dihydrotestosterone propionate (DHTP) plus estradiol benzoate (EB) and that of old sham-operated males given injections of vehicle were observed. The DHTP/EB proved to be less effective overall than the TP in increasing sexual behavior in old castrated males. In a second experiment, young (3 months) and old (30 months) males were tested to verify that the reduced effectiveness of DHTP/EB treatment was age-related. Testosterone propionate and DHTP/EB were equally effective in restoring most measures of sexual behavior in young castrated males. In old castrated males, DHTP/EB treatment was no more or less effective than TP treatment in increasing these same measures. Neither hormone increased the behavior of old males to the level found in young males. Since DHTP/EB treatment is less effective than TP treatment in stimulating sexual behavior in old males, a reduced capacity to aromatize or reduce testosterone is not a likely explanation for decreased responsiveness to testosterone in old male rats.     

Normalization of serum prolactin levels in hemodialysis patients on recombinant human erythropoietin

Correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) has been reported to improve sexual function. As elevated serum prolactin levels are believed to contribute to altered sexual function in uremia, we followed serum prolactin and testosterone levels during four months of r-HuEPO therapy. Within these four months, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly, from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were in the lower normal range in male patients and remained unchanged during r-HuEPO therapy. Sexual function improved in four out of seven males, and five out of nine female patients started to have regular menstruations again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO may improve sexual function by lowering elevated serum prolactin concentrations.     

Social complexity and hormonal influences on sexual behavior in rhesus monkeys (Macaca mulatta)

Rhesus females in multi-animal groups mate only during the mid-follicular and periovulatory portions of their ovarian cycle, whereas females in pair-tests often mate at all cycle phases. We investigated the influence of social context on hormonal mediation of rhesus sexual behavior by observing the same males and females in both pair-tests and in single male/multi-female group-tests. Five intact adult female rhesus were tested with each of four males during their follicular, periovulatory, and luteal cycle phases as verified by steroid radioimmunoassay. Male initiated behaviors of approach, hiptouch, mount, and ejaculation were significantly above luteal levels during periovulatory group-tests, with periovulatory approach and hiptouch frequencies also significantly above follicular levels. Approach did not vary with the female's cycle phase in pair-tests and both follicular and periovulatory frequencies of hiptouch, mount, and ejaculation were higher than luteal levels. Pair-test frequencies were greater than group-test frequencies at all cycle phases, except for male approach, where the difference depended upon female cycle phase. When group-tested, females approached the male, presented, and handslapped most frequently during periovulatory tests. In pair-tests, females approached and handslapped equally during follicular and periovulatory tests and lower luteally, but presents did not vary cyclically. Females approached males significantly more frequently during pair- than group-tests, but there were no consistent differences between the two social conditions for present and handslap. In group-tests, periovulatory females were approached and threatened by other group females significantly more often that they were at other cycle phases. These results demonstrate that the female's hormonal state more clearly influences the sexual behavior of rhesus in multi-female social groups than in pair-tests. This suggests that full expression of hormonal influences on rhesus sexual behavior requires a multi-female social environment and indicates a possible role for competition between females in modulating hormonal influences on sexual behavior.     

Adult sexual behavior deficits and altered hormone levels in male hamsters given steroids during development

Masculine sexual behavior and adult gonadotrophin and steroid hormone levels were assested in intact male hamsters (approximately 100 days old) which had received exogenous steroids on days 2–10 of postnatal life. Estradiol benzoate (EB), testosterone propionate (TP) or testosterone caused deficits in sexual behavior including elimination or decreases in ejaculatory capacity and intromission frequency. Androstenedione or progesterone had no effect on male sexual behavior. EB treatment caused increases in serum LH and FSH levels, normal serum androgen levels and reduced testis weight. TP neonatally administered resulted in decreased serum androgens and decreased testis weight but normal gonadotropin levels. Progesterone did not affect hormone levels or testis weight. Adult castration and TP replacement therapy in males treated neonatally with TP did not reinstate normal levels of ejaculation.     

Suppression of male rhesus testicular function and sexual behavior by a gonadotropin-releasing-hormone agonist

Castrated rhesus monkeys tested in pair tests in small areas mate up to 6 yr after castration, though there is high individual variability (22,23). The generalizability of these findings to social groups in larger areas is unknown. The sexual behavior of 4 adult rhesus males tested singly with a group of 9 intact adult females was examined during short-term, counterbalanced, gonadotropin-releasing-hormone(GnRH)-agonist-induced testicular suppression and control treatment. GnRH-agonist treatment suppressed testosterone to less than 0.6 ng/ml within 16 days. Ten days later (e.g., after 26 days of GnRH-agonist treatment) males were observed for 7 days. The frequency of hiptouches, mounts, intromissons and ejaculations were significantly reduced by testicular suppression. This behavioral reduction was more marked than previously reported in pair-tested castrates during a similar time-period, suggesting testicular suppression more profoundly affects behavior in multifemale groups in larger areas. Males differed in the extent that testicular suppression reduced their sexual behavior. Male ejaculations were completely unaffected in one male and completely eliminated in another. Sexual behavior was reduced less in males with high control levels of testosterone and behavior. Behavioral suppression was unrelated to differences in female behavior and appeared to result from reduced male sexual responsiveness or motivation.     

Sexual behavior in long-term vasectomized male rhesus monkeys.

It has been suggested that in man vasectomy may lead to problems of psychosexual adjustment such as impotency because of castration anxiety or other superstitions often associated with sexual behavior. An increase in sexual promiscuity has also been attributed to vasectomy and has been explained as a loss of fear of impregnating women companions. In monkeys, any alterations in sexual behavior after vasectomy probably are the result, not of cultural factors but of anatomical or immunologic changes resulting from the operation. The sexual behavior of male rhesus monkeys vasectomized 5 years earlier did not differ from that of sham-vasectomized controls. There was, however, a significant difference in the mean latencies to first mount and first intromission; vasectomized males had shorter latencies. In another set of studies, there were no siginificant differences between males vasectomized 12 years earlier (mean) and nonvasectomized controls. We found no association between the presence or absence of antisperm antibodies in the vasectomized males and their levels of sexual performance.     

Stimulus qualities of a preferred female partner and sexual behavior of old rhesus males

A vaginal lavage from a preferred female sexual partner (donor) with whom old (21-27 yr) rhesus males readily copulated or a distilled water lavage was applied to the perineum of non-preferred females (N = 8) with whom old males rarely copulated. The donor and recipients were ovariectomized and were treated with estradiol benzoate (EB) before being tested. Sexual performance of the males did not differ under the two conditions of testing, but the rate of sexual solicitation by the females was significantly higher when treated with the vaginal lavage. One month later the non-preferred females were again treated with EB and paired with the old males. In these tests the preferred female was present in a cage adjacent to and in view of the test pairs. Sexual behavior was not altered significantly, but whereas these males had never threatened or aggressed their partners in previous tests, there was a significant increase in the rate at which they threatened their partners and aggression occurred for the first time. When paired with the preferred female, males ejaculated in 100% of the tests and the average ejaculation latency was less than 2.5 minutes.     

Extra-hypothalamic dopamine is not involved in the effects of hyperprolactinemia on male copulatory behavior

Experiments were performed to determine if the inhibition of copulatory behavior observed in male rats with chronically elevated serum prolactin levels (hyperprolactinemia) is associated with changes in central dopaminergic function in the nigrostriatal and mesolimbic systems. Chronic hyperprolactinemia, induced by ectopic pituitary grafts, inhibited sexual activity but was not associated with changes in locomotor activity, serotyped behavior in response to various doses of apomorphine, or 3H-spiroperidol binding to striatal homogenates. However, open-field defecation was reduced in the pituitary grafted animals. The results of the present study show that changes in nigrostriatal dopamine receptor sensitivity do not contribute to the inhibition of sexual behavior in hyperprolactinemic male rats. In addition, these results also demonstrate that the effects of hyperprolactinemia are relatively specific to copulatory behavior and appear not to involve general behavioral suppression.     

Immune-neuroendocrine interactions during aging: age-dependent thyrotropin-inhibiting activity of thymosin peptides

Thymosin fraction 5 (TF-5), a partially purified thymic preparation, has been previously shown to have luteinizing hormone-releasing hormone (LH-RH)-releasing activity in perfused rat hypothalamus as well as in vivo stimulatory effect on the pituitary-adrenal axis in prepubertal monkeys. We report here the effect of TF-5 on the TSH-thyroid axis in young (3 months) and old (25 months) Sprague-Dawley male rats. Conscious free-moving animals carrying an indwelling atrial cannula received a single dose of 5 mg/kg body wt. of either bovine serum albumin (BSA) or TF-5 via the cannula. In the young rats, TF-5 induced a marked reduction of plasma thyrotropin (TSH) which was significantly greater than the normal circadian decline observed in the BSA-treated controls. The old males displayed high basal levels of TSH which showed no circadian rhythmicity, and did not respond to TF-5. Thyroxine (T4), triiodothyronine (T3), corticosterone, and prolactin levels were not affected by TF-5 at the dose levels tested. The old rats had significantly lower basal levels of T4, but not T3, than their young counterparts. The synthetic peptides thymosin alpha-1 and serum thymic factor, which are components of TF-5, had no effect on the above hormones when injected in doses up to 5 micrograms/kg body wt. Acute thymectomy in 3-month-old males induced a significant increase in basal levels of TSH without affecting plasma T4 or T3. These results suggest that the thymus has an inhibitory action on TSH in the rat, which is not mediated by the thyroid gland.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sexual behavior of male rats is differentially affected by timing of perinatal ACTH administration.

The laboratory rat was used as a model to investigate the effect of pre- and/or postnatal ACTH administration on sexual differentiation of the brain. Pregnant Sprague-Dawley rats were injected with ACTH 1-24 (10 micrograms/kg/2x/day or 500 micrograms/kg/2x/day); postnatally treated neonates were injected with the above dosages once a day. Perinatal treatment with ACTH (10 micrograms/kg/2x/day) altered several sexual behavior measurements, but did not have an overall effect on the number of males that exhibited sexual behavior. At a higher dose (500 micrograms/kg/2x/day) prenatal ACTH administration decreased sexual behavior in male rats, as measured by an increase in the percent of males that did not mount or intromit. In contrast, all males treated postnatally with ACTH (500 micrograms/kg/2x/day) completed 2 ejaculatory series and initiated a third series. No significant differences were observed in adult plasma testosterone or prolactin levels; however, serotonin levels in the preoptic area of adult male rats treated prenatally with ACTH (500 micrograms/kg/2x/day) were significantly higher than in prenatally treated saline males. In addition, an increase in plasma ACTH in adulthood was observed in animals injected postnatally with saline. This study indicates that the decrease in sexual behavior observed in males treated prenatally with ACTH is associated with increased serotonin levels in the preoptic area, which suggests that ACTH may act as a neuromodulator during sexual differentiation of the brain. It also demonstrates that the effect of perinatal manipulations on the development of male sexual behavior may vary depending on the ontogenetic period of the brain.     

Plasma levels of growth hormone correlate with the severity of pathologic changes in the renal structure of aging rats.

It is well known that pharmacologic administration of growth hormone (GH), prolactin (Prl) or adrenal steroids can induce nephrosclerotic lesions in rodents. In this study we correlated circulating levels of endogenous GH, Prl, and corticosterone with the degree of structural nephropathy in rats of different ages. Female young (3 to 4 months), old (25 months), and senescent (33 to 35 months) and male young (3 to 4 months) and old (24 to 26 months) Sprague-Dawley rats were used. Sequential blood samples were removed through intraatrial cannulas while the animals remained conscious and undisturbed. Plasma Prl showed a 3-fold increase in old compared with young males, while old and senescent females displayed a 13- and 64-fold increase, respectively, for Prl. Plasma GH decreased significantly in old compared with young males, while senescent females had elevated GH levels compared with their young and old counterparts. Plasma corticosterone showed an age-related decline in females but not in males. The kidneys from old males showed a marked degree of glomerular sclerosis and obliteration. The presence of tubular metaplasia of Bowman's capsule as well as deposits of iron in the tubular epithelium was common in old males but rare in old and senescent females. There was a strong correlation of plasma GH, but not Prl, with the severity of renal histopathology. Plasma corticosterone showed an inverse correlation with the severity of renal histopathology in old males and senescent females. These results are consistent with the hypothesis that GH contributes to nephrosclerosis of aging rats, whereas the role of corticosterone and Prl in the pathogenesis of these lesions remains unclear.