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.

Chronic gonadotropin-releasing hormone agonist treatment suppresses ovulation and sexual behavior in group-living female rhesus monkeys.

The sexual behavior of six adult rhesus females was observed with each of four males prior to, during, and following a 90 day treatment with 20 micrograms/day of a gonadotropin releasing-hormone (GnRH) agonist (WY-40972). All females ovulated, approached males and copulated during an untreated cycle. No ovulations occurred during agonist treatment and all females showed reduced sexual interest during the last 25 treatment days. Three females showed elevated estradiol and copulated during the first 10 days of agonist treatment, but never showed similar levels of estradiol or copulation during the rest of treatment. Within 34 days after agonist treatment, all females initiated proximity to males, copulated, and ovulated. All females became pregnant on their second ovulation after agonist treatment. This demonstration that inhibition of ovulation with a GnRH agonist decreased rhesus female sexual initiation, demonstrates the importance of ovarian hormones to female sexual motivation and suggests that the changes in human female sexual interest should be evaluated during the development of agonist-based contraceptives.

Periovulatory changes in female sexual behavior and patterns of ovarian steroid secretion in group-living rhesus monkeys.

The behavior of nine intact group-living adult female rhesus was observed for 30 min daily with each of four adult male rhesus across a verified ovulatory menstrual cycle. Blood samples collected from females daily or on alternate days were analyzed for estradiol, testosterone, and progesterone. Female patterns of approach, follow, and initiate proximity increased several days prior to the estradiol peak, peaked on the day of the estradiol peak, then declined completely or to very low frequencies. Mounts, intromissions, and ejaculations increased significantly on the day of the estradiol peak, remained elevated for 2 more days, then declined completely by the fifth day after peak estradiol. Ejaculations never occurred outside of a 10-day period starting 4 days before the estradiol peak and ending 5 days after the estradiol peak. During this period females initiated over 90% of all approaches. Female hand slap, threaten away, and stand up increased significantly on the first day of increased copulation, remained elevated while copulation was significantly elevated, then decreased along with the decline in copulation. Ten of eleven patterns of female behavior correlated significantly with estradiol level prior to the estradiol peak. All were significantly inversely correlated with progesterone level after the estradiol peak. No pattern of female behavior correlated significantly with testosterone either before or after the estradiol peak. Similarly, male patterns of behavior correlated with female levels of estradiol and progesterone, but not testosterone. These results demonstrate a relationship between increased serum estradiol and increased female initiation of sexual behavior. The finding that some patterns of female behavior increase several days prior to copulation, whereas other behaviors increase coincident with increased copulation suggests that the behavior of group-living rhesus females serves two functions. The first is to communicate sexual interest and the second is to maintain the consort pair and increase the probability that ejaculation will occur. In addition, the strong correlation between preovulatory female behavior and estradiol level suggests that the female's behavior provides precise information about her reproductive state and could thus coordinate copulation with maximal fertility.

Blockade of neonatal activation of the pituitary-testicular axis with continuous administration of a gonadotropin-releasing hormone agonist in male rhesus monkeys.

The objective of this study was to determine the effects of continuous GnRH agonist (Ag) treatment on neonatal activation of the pituitary-testicular axis in male rhesus monkeys. Five infants were treated continuously with Ag(10 micrograms/day; Wy-40972) for 112 days using osmotic minipumps beginning at 10-13 days of age. Two of five age-matched control animals were implanted sc with Silastic implants of comparable size to the minipumps; three did not receive sham implants. Ag treatment caused a fall in serum LH (bioassay) values to undetectable levels (much less than 0.1 micrograms/ml) within 3 weeks, where they remained throughout Ag treatment. Mean serum testosterone (T) levels fell from pretreatment values of 1.52 +/- 0.45 to 0.38 +/- 0.09 (+/- SE) ng/ml after 3 weeks of Ag treatment. The level of T never exceeded 0.60 ng/ml throughout the subsequent course of Ag treatment. In contrast, serum LH and T were elevated to levels that approached adult values during the first 2 postnatal months in control infants with or without sham implants. Both LH and T then gradually declined, and by 4 months of age, T levels were indistinguishable from those in Ag-treated animals. Control infants had an increase in serum LH from 0.56 +/- 0.10 to 2.67 +/- 0.49 micrograms/ml within 60 min of administration of 5 micrograms GnRH/kg BW at 60 days of age. Serum T values rose from 2.35 +/- 1.00 to 9.48 +/- 3.15 ng/ml during the same period. Seven weeks of Ag treatment abolished the LH and T responses to GnRH. Thirty days after the termination of Ag treatment (approximately 150 days of age), Ag-treated and control infants had comparable serum LH and T responses to GnRH, although the responses were reduced relative to the responses in controls at 60 days of age. These results suggest that continuous administration of Ag desensitizes the pituitary of the male infant rhesus monkey to GnRH and blocks neonatal activation of the pituitary-testicular axis.