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D Zumpe

Publications and source records attributed to D Zumpe.

At least 19 recordsLinked to original sources
PubMed1992

The interaction of testosterone with the brain of the orchidectomized primate fetus.

At certain times during gestation, the testes of the fetal macaque produce plasma levels of testosterone (T) that are similar to those of adults. It is thought that testosterone acts on the brain via estrogen and androgen receptors to organize the development of sexually dimorphic neural structures that underlie sex differences in behavior. To test the proposition that there are male-female differences in the occupation of steroid receptor binding sites during fetal development in the cynomolgus macaque, we have compared the uptake of [3H]T and its metabolites in: (1) 5 intact males (plasma T 571.2 +/- 215.5 ng/100 ml); (2) 5 intact females (33.8 +/- 25.2 ng/100 ml); (3) in 5 males orchidectomized in utero (14.6 +/- 5.7 ng/100 ml). About 1 week after fetal gonadectomy or sham-operation, all fetuses were given 500 microCi [3H]T s.c. and were then delivered 60 min later by Cesarean section. Brains were removed and dissected into blocks containing the hypothalamus and preoptic area, amygdala, hippocampus, and midbrain. Samples of cerebral and cerebellar cortex were also obtained. Purified nuclear pellets were prepared by centrifugation through 2 M sucrose and were extracted into ether and analyzed by high performance liquid chromatography. Hypothalamic nuclear concentrations of [3H]E2 in intact males (847 +/- 195 dpm per mg DNA) were significantly lower than those in sham-operated females (2147 +/- 542 dpm per mg DNA) (P less than 0.05), but those in orchidectomized males (2233 +/- 345 dpm per mg DNA) were similar to concentrations in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Medroxyprogesterone acetate, aggression, and sexual behavior in male cynomolgus monkeys (Macaca fascicularis).

Medroxyprogesterone acetate (MPA) is used clinically to treat male sex offenders, but there are conflicting reports about its effects on aggression. To investigate these matters in a nonhuman primate, four intact male cynomolgus monkeys were studied in a testing paradigm that involved the presence of a caged, aggression-arousing stimulus male either immediately before or during a pair-test with an ovariectomized, untreated female partner. After two 4-week periods of pretreatment baseline, males received weekly injections of 40 mg MPA either alone (two 4-week treatment periods) or in combination with testosterone replacement with sc implants (one period) and additional daily injections of 2 mg testosterone propionate (two periods). MPA was then withdrawn while testosterone replacement continued (three periods). The testing paradigm was effective in maintaining aggression, especially male-male aggression, for many months. Male-male aggression increased with MPA treatment, and increased further with testosterone replacement, whereas male-female aggression tended to change in the opposite direction. As in earlier studies, MPA decreased both plasma testosterone and male sexual activity, but restoring plasma testosterone levels in treated males failed to restore their sexual activity. MPA therefore has behavioral effects that are not mediated primarily by its suppression of circulating androgens.

Aggression↗
PubMed1991

Medroxyprogesterone acetate and the nuclear uptake of testosterone and its metabolites by brain, pituitary gland and genital tract in male cynomolgus monkeys.

The synthetic progestin, medroxyprogesterone acetate (MPA), is used to treat male sex offenders, and it is also suppresses sexual activity in male monkeys. To examine the possibility that MPA may act as an anti-androgen in the primate brain, 4 intact male cynomolgus monkeys were given MPA (40 mg i.m.) once a week for 16 weeks, while 4 control males received i.m. injections of vehicle. All males were then castrated and 3 days later were given 3 mCi [3H]testosterone ([3H]T) i.v.; 1 h after injection males were killed, and radioactivity in nuclear pellets obtained from the hypothalamus (HYP), preoptic area (POA), amygdala (AMG), septum, pituitary gland and genital tract was analyzed by HPLC. Concentrations of [3H]T and [3H]dihydrotestosterone in nuclear pellets were 65-96% lower in MPA-treated males than in controls (P less than 0.001), but the aromatized metabolite, [3H]estradiol, which was the major form of radioactivity present in nuclear pellets from HYP, POA and AMG, was unchanged. There were no differences in concentrations of [3H]T in supernatants from the tissues of MPA-treated and control males. Because the reduced nuclear uptake of androgen in brain occurred in males whose androgen-dependent behavior had been suppressed by MPA treatments, it is proposed that MPA may have anti-androgenic effects at the level of the cell nucleus in brain regions that control behavior.

Animals↗
PubMed1990

Estradiol administration and the sexual activity of castrated male rhesus monkeys (Macaca mulatta).

To examine whether estradiol might be effective in maintaining sexual behavior after castration or after testosterone withdrawal, we have observed male rhesus monkeys during daily 1-hr tests alternately with each of two ovariectomized, estradiol-treated females (four males, four females, eight male-female pairs, 798 tests). Estradiol (2-5 micrograms/kg sc/day) or vehicle was administered in counterbalanced order immediately after castration and again immediately after withdrawal of testosterone propionate treatments (800 micrograms and 1.6 mg sc/day). There were no significant differences in behavior during vehicle and estradiol treatments to indicate that estradiol helped to maintain male sexual activity. Instead, estradiol treatment tended to interfere with the capacity to intromit. This supported the results of other studies, namely, that the systemic administration of estradiol does not enhance the sexual behavior of castrated male macaques, and raises questions about the role of both aromatization and estrogen receptors in the male primate brain.

Animals↗
PubMed1990

Comparisons of the nuclear uptake of [3H]-testosterone and its metabolites by the brains of male and female macaque fetuses at 122 days of gestation.

Testosterone secreted by the testis of the macaque fetus is thought to influence certain aspects of the brain's subsequent development which may be responsible for the ontogeny of sexually dimorphic patterns of behavior. To compare the interactions between testosterone and the receptors for androgens and estrogens in brain cell nuclei in the two sexes, 7 intact female fetuses and 5 intact male fetuses were injected in utero at about 120 days of gestation with [3H]-testosterone (250 microCi i.v. or 500 microCi s.c.). One hour later, fetuses were delivered by cesarean section, and samples of brain and peripheral tissues were homogenized and separated into purified nuclear and supernatant fractions. Fractions were analyzed by high performance liquid chromatography to measure levels of [3H]-testosterone and its metabolites. Concentrations of radioactivity extracted from cell nuclei were significantly higher in the hypothalamus-preoptic area than in other brain areas (p less than 0.001); [3H]-estradiol represented 65.0 +/- 5.7% of this radioactivity and nuclear concentrations of this metabolite were 73% lower in males than in females (p less than 0.001). Nuclear concentrations of [3H]-testosterone in the pituitary gland (68.9 +/- 8.8% of extracted radioactivity) were 48% lower in males than in females (p less than 0.001). There was no evidence of a sex difference in the tissue uptake of radioactive steroids from blood, but in males, levels of endogenous plasma testosterone (599.8 +/- 208.2 ng/100 ml) were significantly higher than in females (37.7 +/- 28.5 ng/100 ml; p less than 0.01), and the specific activity of [3H]-testosterone in blood was consequently lower in males than in females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effects of medroxyprogesterone acetate on plasma testosterone and sexual behavior in male cynomolgus monkeys (Macaca fascicularis).

Medroxyprogesterone acetate (MPA), a synthetic progestin with androgen-depleting activity, is used to treat the deviant sexual behavior of men. To investigate the effects of MPA in another anthropoid primate, 16 oppositely-sexed pairs of cynomolgus monkeys were observed in one-hour behavior tests during 15 successive 4-week periods conducted before, during and after administering to males weekly IM injections of first 20 mg and then 40 mg MPA. The doses used were comparable on a body weight basis to those employed clinically. Blood samples were collected weekly and assayed for plasma testosterone. During MPA treatment both plasma testosterone and ejaculatory behavior were significantly decreased, but the changes in behavior were less marked than the changes in hormone levels. There were clear differences between individual males in the effects of treatment, and the identity and hormonal status of the female partners also influenced the results. During the 6 month withdrawal period, effects were only partially reversible, and the data suggested that the behavioral changes depended on the hormonal changes rather than the opposite. However, a direct central action of MPA on behavioral mechanisms could not be excluded.

Animals↗
PubMed1987

Testosterone and its metabolites in male cynomolgus monkeys (Macaca fascicularis): behavior and biochemistry.

To extend our previous study on the behavioral effects of testosterone propionate (TP) and dihydrotestosterone propionate (DHTP) to a dose-range producing supra-physiological plasma androgen levels, 4 castrated cynomolgus monkeys were tested with the same 4 females during successive 4-week treatment periods while receiving 800 micrograms, 1.6 mg, 3.2 mg, 6.4 mg and 12.8 mg of TP or DHTP SC/day in counterbalanced order (16 pairs, 828 1-hr tests). Both androgens increased male sexual activity, but DHTP was less effective than TP in increasing the numbers of ejaculations per test and failed to restore ejaculations to intact levels. Giving androgen-treated males single injections of 50 micrograms and 100 micrograms estradiol benzoate (EB) was without any additional effect on behavior (16 pairs, 256 tests). To examine hormonal effects in the brain, castrated males were given either 3H-T or 3H-DHT, and tissues were examined by high performance liquid chromatography (hplc). After 3H-T, 3H-E2 and unchanged 3H-T were the major forms of radioactivity in nuclei from hypothalamus, preoptic area and amygdala. After 3H-DHT, unchanged 3H-DHT predominated. The lower behavioral effectiveness of DHT could not be ascribed to its failure to enter the brain. The data suggested a role for unchanged T in the regulation of ejaculatory behavior in a male primate.

Animals↗
PubMed1986

Comparison of the effects of testosterone and dihydrotestosterone on the behavior of male cynomolgus monkeys (Macaca fascicularis).

To compare the behavioral effects of testosterone propionate (TP) and diyhdrotestosterone propionate (DHTP) at doses producing plasma levels of androgens within the physiological rage, observations were made on 4 castrated male cynomolgus monkeys during successive 4-week treatment periods while they received 25, 50, 100, 200, 400 and 800 micrograms of either TP or DHTP SC/day in counterbalanced order. Males were tested with each of the same 4 female partners (16 pairs, 1024 1-hr behavior tests). Males were injected at 1600 hr and blood samples were obtained at 0800 hr (256 samples, 456 hormone determinations). Physiological plasma levels of T resulted from the 200 micrograms and 400 micrograms TP treatments, and were associated with significantly increased ejaculatory behavior. Physiological plasma levels of DHT resulted from the 50 micrograms and 100 micrograms DHTP treatments, but there were no changes in ejaculatory behavior over the entire DHTP dose range used. This difference in the behavioral effects of TP and DHTP, not previously reported for a primate, could not be accounted for by the effects of treatment order, season, long-term behavioral testing, female sexual motivation or behavior reflecting the peripheral action of androgens.

Animals↗
PubMed1986

An annual rhythm in the battering of women.

Over 27,000 reports about women abused by their live-in male partners were provided by 23 shelter organizations in five locations in the United States. Cosinor analyses revealed statistically significant annual rhythms in the frequencies of abuse, with maxima in the summer. The rhythms were closely related to annual changes in ambient temperature in these locations, and the time of the maxima was similar to those previously reported for assaults and rapes. The findings support the hypothesis that violence by men toward women increases in summer independently of any major seasonal changes in the opportunity for contact between perpetrator and victim.

Aggression↗
PubMed1985

Effects of testosterone on the behavior of male cynomolgus monkeys (Macaca fascicularis).

To determine the threshold doses of testosterone propionate (TP) that cause clear-cut behavioral changes in the sexual behavior of castrated male cynomolgus monkeys, observations were made on three males during successive 5-week treatment periods while they received daily subcutaneous doses of 100 micrograms TP increasing in octaves to 25.6 mg TP. Males were tested with each of the same two ovariectomized, estrogen-treated females (6 pairs, 330 1-hr behavior tests). To mimic the diurnal plasma testosterone rhythm, TP injections were given at 1600 hr and blood samples were obtained at 0800 hr (141 samples). Male ejaculatory activity increased at the threshold dose of 200 micrograms TP per day giving plasma testosterone levels of 830 ng/100 ml, which is in the physiological range of 600-1600 ng/100 ml for intact males. This threshold dose was eight times higher than in rhesus monkeys on a dose per kilogram body weight basis. There was a further marked increase in ejaculatory performance at higher doses (6.4 to 25.6 mg) giving supraphysiological plasma levels of 4000-9000 ng/100 ml. There were individual differences in the behavioral changes occurring with TP treatment, and the female partner modulated the effects. These findings were generally similar to those obtained with male rhesus monkeys, but certain species differences were noted.

Animals↗
PubMed1978

Potency in male rhesus monkeys: effects of continuously receptive females.

Ejaculations decreased and mount latencies increased when intact males were paired regularly over a 3.5-year period (3180 tests) with ovariectomized females made constantly receptive by daily injections of estradiol. The deterioration in potency was abruptly and completely reversed by substituting a group of new but similarly treated females for the original ones.

Animals↗
PubMed1978

Menstrual cycle influences on operant behavior of female rhesus monkeys.

Nine female rhesus monkeys were paired with males throughout 63 menstrual cycles. The females' motivation to approach males was studied with an operant conditioning paradigm that required the female to press a lever 250 times to gain access to the male. Sexual behavior was scored during standard 60-min tests that followed the attainment of access (17 pairs, 1,440 tests). In the overall data, mean times to access were shortest at mid-cycle and longest just before and after the onset of menstruation, and a model-fitting method showed that 45% of cycles from individual pairs were significantly correlated with a V-shaped model of the overall pattern. Male sexual activity was highest at mid-cycle and lowest in the last quarter of the cycle, but the changes in access times could not be attributed entirely to the rewarding effects of the ejaculations. In the combined data from five females (9 pairs, 33 cycles), high estradiol levels and low progesterone levels were statistically associated with short access times and short ejaculation times. The overall effect was for operant performance and sexual activity to be synchronized and maximized in the periovulatory period of the menstrual cycle.

Animals↗
PubMed1977

Effects of androgen administration on sexual invitations by female rhesus monkeys (Macaca mulatta).

Pairs of adult rhesus monkeys of opposite sexes (12 pairs) were studied during 1-h mating tests (986 tests). Ovariectomized females received 5 microgram oestradiol intravaginally throughout to keep them attractive to males and maintain a relatively constant level of male sexual activity. Females were given subcutaneous silastic implants of testosterone to change their sexual receptivity. A threefold change in sexual invitations resulted from the implantation and removal of testosterone in the absence of any major changes in the behaviour of their male partners. These changes in invitational behaviour therefore reflected an action of the hormone upon an internal mechanism within the female subserving sexual motivation which was independent of changes in the behaviour of the male. Radioimmunoassay of plasma testosterone (109 samples) and plasma oestradiol (86 samples), and gas-liquid chromatography of vaginal secretions (306 samples), facilitated the monitoring of variables needed to interpret the results.

Animals↗