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PubMed1983

Effects of castration and sex hormones on immune clearance and autoimmune disease in MRL/Mp-lpr/lpr and MRL/Mp-+/+ mice.

The clearance of erythrocytes sensitized with IgG was studied in MRL/Mp-lpr/lpr (MRL-lpr) and MRL/Mp-+/+ (MRL-+/+) mice, which spontaneously develop autoimmune disease. In both strains, an age-dependent decline in clearance of IgG-sensitized erythrocytes was found. Impaired clearance occurred at an earlier age in MRL-lpr mice than in MRL-+/+ mice, correlating with the relative severity of autoimmune disease in these strains. Androgen treatment improved clearance in MRL-+/+ mice but not in MRL-lpr mice, even though autoantibody levels, renal function, and survival were improved. These results suggest that the beneficial effects of androgen on autoimmune disease are not due solely to improved clearance of immune complexes. Castration followed by estrogen administration did not influence immune clearance or autoimmune disease in MRL-lpr mice. These results indicate that impaired immune clearance is a common feature in several autoimmune mouse strains. However, the effects of sex hormones on immune clearance and autoimmune disease may be dissociated in some strains.

Animals↗
PubMed1975

Postpuberal castration and prostatic carcinoma.

The occurrence of prostatic carcinoma after postpuberal castration is rather unique since only one other case has been reported. However, there was no lack of androgens in the patient in this report, because the testicular ablation was compensated by nodular hyperplasia of the adrenal cortex maintaining a normal plasma testosterone.

Adenocarcinoma↗
PubMed1975

Effect of castration, testosterone treatment and hereditary sterility on prostaglandin concentration in the male reproductive system of mice.

The concentration of prostaglandins E and F in different parts of the male reproductive system of CD-1 and dwarf mice was measured by radioimmunoassay. In intact CD-1 mice, the vas deferens contained a significantly higher concentration of PGE and PGF than was found in the epididymis and in the seminal vesicles. All tissues studied had more PGE than PGF. Castration resulted in increased PG concentrations in both the epididymis and the seminal vesicles and decreased PG concentrations in the vas deferens. There was also a differential response of PGE and PGF in the epididymis of genetically sterile dwarf mice (dw/dw) were significantly higher than those observed in their normal littermates ((PLUS)). A reversed PGE/PGF ratio was found in the mates. The results indicate that testicular androgens affect the levels of PGE and PGF in the reproductive system of male mice. The physiological role of PGs in male reproductive functions has not been established, but there is a suggestion that PH have a role in controlling the transit of spermatozoa through the epididymis and vas deferens.

Animals↗
PubMed1985

Inhibition of mating by naloxone or morphine in recently castrated, but not intact male rats.

Administration of naloxone (SC 5 mg/kg) significantly reduced ejaculation and mounting in male rats in the weeks following castration. A similar effect was obtained by injecting morphine (SC 1 or 5 mg/kg). In contrast, the same dosages of naloxone or morphine did not affect the sexual performance of gonadally intact males. Opioid peptides may contribute to the temporary persistence of sexual behavior in testosterone-deficient male mammals, in which incentive qualities of the female partner are an important determinant of sexual arousal.

Animals↗
PubMed1985

Effects of neonatal castration or treatment with dihydrotestosterone on numbers of neurons in the rat superior cervical sympathetic ganglion.

There is a normal sexual dimorphism in the number of neurons in the rat superior cervical sympathetic ganglion (SCG), with adult males having more neurons in this ganglion than females. We confirm this finding here, report that this sex difference is not present at birth and that neonatal castration of males reduces the adult sex difference. These results indicate that perinatal levels of circulating testicular hormones play a role in regulating the numbers of neurons in the SCG. Treatment of neonatal rats with testosterone propionate or estradiol significantly increases the number of neurons in the SCG. To determine whether this effect is primary androgenic or estrogenic, the effects of dihydrotestosterone, on SCG neuron number were investigated. Dihydrotestosterone, unlike testosterone, is not aromatized to estradiol intracellularly. There was no difference in the number of neurons between animals injected from birth with vehicle or dihydrotestosterone. This difference in effects between dihydrotestosterone and testosterone suggests that the actions of testosterone may be via aromatization to estradiol, rather than action at an androgen receptor.

Animals↗
PubMed1996

Effects of acute and chronic cocaine administration on EEG and behaviour in intact and castrated male and intact and ovariectomized female rats.

Intact and gonadectomized male and female WAG/ Rij rats were used to study the effects of gender and gonadal hormones on the development of sensitization and tolerance to cocaine-induced changes in EEG and behaviour. The four groups of WAG/Rij rats differed in the number of spontaneously occurring spike-wave discharges: ovariectomy decreased and castration increased the number of spike-wave discharges. This confirms that testosterone has antiabsence effects and that female gonadal hormones may promote the occurrence of spike-wave discharges. Cocaine [10 and 20 mg/kg, intraperitoneally (IP)] was administered before and after chronic cocaine administration (9 days, one daily injection with 10 mg/kg) and EEG and behaviour were monitored. Cocaine strongly suppressed the occurrence of spike-wave discharges before and after chronic administration in all four groups, although the decrease was less in the intact males. Sensitization or tolerance induced by cocaine on EEG could not be established. Acute cocaine administration eliminated explorative, automatic, and passive behaviour, whereas various stereotypical activities such as uncoordinated head and body movements and head swaying emerged. Differences between groups were observed as intact males were less likely than subjects in the three other groups to engage in intense stereotyped behaviour. These data suggest that testosterone inhibits EEG and behavioural effects of acute cocaine administration. All four groups displayed less head swaying and more uncoordinated head and body movements after chronic cocaine administration, suggesting that behavioural sensitization had occurred. Differences between the four groups had faded away. Although pharmacokinetic differences in levels of cocaine and benzoylecgonine between the four groups were found, they could not easily be related to the behavioural differences between groups.

Animals↗
PubMed1987

Lighting conditions affect the levels of plasma gonadotropins differently in old and young castrated male rats.

It has been suggested that the decreased plasma levels of FSH and LH, often found in old male rats, are due to a diminished adenohypophyseal capacity to secrete the hormones and/or by changes in the hypothalamic regulatory system. We studied the effect of varying lighting conditions (12/12 h LD, continuous light and continuous darkness) on the plasma levels of the gonadotropins in castrated young adult and old male rats. We expected the sensitivity of the regulatory system to light to decrease or disappear with aging. The results for FSH supported this hypothesis: the plasma levels of FSH were more stable to changes of lighting conditions in the old rats. In disagreement with our hypothesis, the levels of LH were more sensitive to light changes in old than in young rats. It was concluded that the regulatory systems of the two hormones vary differently with age.

Aging↗
PubMed2004

Long-term persistence of male copulatory behavior in castrated and photo-inhibited Siberian hamsters.

Gonadal steroids are essential for the long-term maintenance of the full repertoire of sexual behavior in male rodents. Typically, all individuals of several species cease to display the ejaculatory reflex within a few weeks of castration. The present study documents the persistence of the ejaculatory reflex 19 weeks after orchidectomy in 40% of male Siberian hamsters maintained in long or short day lengths; testosterone was undetectable in the circulation of these animals. Intact hamsters transferred from a long to a short photoperiod underwent gonadal regression: 50% of these animals continued to display mating behavior culminating in ejaculation throughout 25 weeks of testing. The remaining animals failed to ejaculate after approximately 11 weeks of short day treatment but resumed mating coincident with spontaneous gonadal recrudescence. Activation of sex behavior in the latter cohort appears to depend on gonadal steroids and is in contrast to the copulatory behavior of the substantial proportion of the study population that sustains the full sexual repertoire in the long-term absence of gonadal steroids. Sex behavior of the latter animals may be dependent on nongonadal steroids or mediation by steroid-independent mechanisms.

Adaptation, Physiological↗
PubMed1981

Human chorionic gonadotropin blocks the estrogen-induced luteinizing hormone release in long-term castrated rhesus monkeys: evidence for an ultrashort-loop negative feedback.

We studied the effects of human chorionic gonadotropin (hCG) administration on the biphasic response of luteinizing hormone (LH) to estrogen challenge in long-term castrated, female rhesus monkeys. Estradiol benzoate (EB), 400 micrograms, was administered to all animals at time zero; hCG, 2000 IU, was administered either concomitantly or 12 hours after EB. Blood samples were obtained every 6 hours for 58 hours, and then at 72 and 82 hours. Control animals received EB alone. Serum LH and beta hCG were determined by radioimmunoassay. Control animals showed a typical biphasic response to EB: an initial decrease in LH levels, 50% to 70% of baseline, from +6 hours until +30 hours; then a large increase, 150% to 190% of baseline, at +48 hours. Animals treated with hCG at time zero showed an initial decrease in LH, 40% to 70% of baseline, but LH returned to basal levels at +42 hours. Animals treated with hCG 12 hours after EB showed an initial decrease in LH, 45% to 55% of baseline, but LH returned to basal levels at +36 hours. These results suggest that an LH ultrashort-loop negative feedback may exist in the nonhuman primate.

Animals↗
PubMed1975

Suppression of plasma androgens by spironolactone in castrated men with carcinoma of the prostate.

Spironolactone, an inhibitor of androgen synthesis, has been administered to castrated men with metastatic carcinoma of the prostate. Plasma levels of testosterone, androstenedione and dehydroepiandrosterone were significantly decreased. These data indicate that spironolactone suppresses adrenal androgen production and suggest that it may be of benefit in the treatment of orchiectomized patients with advanced carcinoma of the prostate.

Aged↗
PubMed1984

Effect of sex and castration on nicotine-induced activity responses.

The nature of the short-term interactions between nicotine and sex hormones in affecting activity remain unclear. The present study was an investigation of these effects. Three levels of nicotine injection--0.0 (saline control), 0.2 mg/kg body weight, and 0.4 mg/kg body weight-were given to male, female, and castrated Sprague-Dawley albino rats. Activity was measured when the animals were 6 weeks and 12 weeks old. Nicotine produced an initial depression of activity relative to the saline control levels, and a later activation which peaked at 40 to 60 minutes. The biphasic effect was most striking in female animals, but the forms of the curves relating activity to time in all groups were quite similar.

Animals↗
PubMed1998

Neither castration nor steroid-replacement change the apparent molecular size of FSH in the sheep pituitary.

Gonadal steroids alter the apparent molecular size of intrapituitary Follicle-Stimulating Hormone (FSH) in rats and monkeys as well as increase the percentage of acidic FSH isohormones in sheep. Hence, we hypothesized that the molecular size of ovine (o) FSH would be increased by gonadal steroids. Extracts of pituitaries from rams and wethers, as well as, from wethers which had been implanted with dihydrotestosterone (DHT), 17 beta-estradiol (E2) or both steroids (n = 4-6 per treatment group) were subjected to analytical gel permeation chromatography using Sephadex g-100 Superfine. FSH concentrations in chromatographic fractions were determined by radioimmunoassays. Although FSH in pituitaries of non-implanted wethers eluted slightly earlier (i.e. larger) than FSH in pituitaries from E2-implanted wethers as evaluated by distribution coefficients (Kds) during chromatography (P < 0.05), gonadal steroids did not consistently increase Kds but tended to decrease them. When Kds were extrapolated to apparent molecular weights using a series of standard proteins (bovine serum albumin (bSA), ovalbumin (OA), carbonic anhydrase (CA) and cytochrome c (CC)) that were included in each chromatogram, the differences between treatment groups were not statistically significant (P > 0.05). Thus, in contrast to rats and monkeys, neither castration nor steroid-replacement appears to alter the molecular size of FSH in the sheep pituitary as evaluated by analytical gel permeation chromatography.

Animals↗
PubMed1999

Effects of megestrol acetate and testosterone on body composition in castrated male Sprague-Dawley rats.

The interrelationships among sex hormones, caloric intake, and intermediary metabolism in health and disease are uncertain. Studies in malnourished patients with AIDS and cancer show that megestrol acetate (MA) therapy increases appetite, body weight, and body fat, while it decreases serum testosterone (T) concentration. In this study, the separate and combined effects of MA and T were investigated in 65 young adult, male, castrated, Sprague-Dawley rats who received subcutaneous implants containing placebo, MA, T, or both MA and T for 11 wk. By hierarchical multiple regression analysis, MA therapy decreased weight gain and food intake (P < 0.01), increased body fat (P = 0.024), decreased body protein (P < 0.001), and decreased the portion of calories accrued as protein rather than fat (P ratio, P < 0.03). T alone decreased fat (P < 0.03), but had no significant effect on food intake, the relative number of consumed calories utilized for growth (food efficiency), body weight, or protein. The interaction of MA and T did not affect food intake or food efficiency, but increased body weight (P < 0.02), protein (P < 0.05) and the P ratio (P < 0.02). The portion of weight gain as fat was reduced from 47.3% with MA alone to 27.4% when MA and T were combined. Thus, megestrol acetate has significant antianabolic effects that are independent of its effects upon food intake. The addition of testosterone to megestrol acetate partially antagonized MA's inhibition of lean mass accretion in these rats.

Animal Nutritional Physiological Phenomena↗
PubMed1984

Experimental infection of castrated lambs with Mycoplasma agalactiae.

The course of experimental infection in groups of 6-month-old castrated lambs with field isolates of Mycoplasma agalactiae from France was followed culturally and serologically for 7 months. Infection with an ovine field isolate following inoculation by different routes and contact exposure was compared with that caused similarly by a caprine field isolate. The prolonged infections produced were symptomless apart from limited arthritis in one animal inoculated with the isolate from sheep and increased lachrymation in another associated with the goat isolate. The ovine isolate was more virulent in that ante- and post-mortem recoveries of the organism were more consistent and the serological responses more pronounced. Serological responses varied between animals and between strain infections, and the results of the film inhibition test were more consistent than those of the complement fixation test. The limitations of both these tests for detecting carrier infections are discussed.

Animals↗
PubMed1996

Comparison of the effects of 17 alpha-methyltestosterone, methandrostenolone, and nandrolone decanoate on the sexual behavior of castrated male rats.

In a series of 3 experiments, adult male Long-Evans rats were castrated and treated with 1 of 3 different anabolic-androgenic steroid (AAS) compounds (17 alpha-methyltestosterone, methandrostenolone, or nandrolone decanoate) for 6 weeks. In each experiment, subjects received daily injections of a high, medium, or low dose of AAS or the oil vehicle. The AAS effects on body weight in gonadectomized male rats were modest, and no effects on locomotor activity were observed. The AAS compounds administered at doses comparable with human abuse levels were not equipotent in maintaining male sexual behavior patterns (nandrolone decanoate > methandrostenolone > 17 alpha-methyltestosterone). In addition, the behavioral actions of AAS compounds did not parallel stimulation of sexual accessory glands. The authors reported that this study is the first to quantify the dose-response characteristics of individual AAS compounds with regard to these behavioral and endocrine measures.

Anabolic Agents↗
PubMed1983

Gonadal hormone activation of male courtship ultrasonic vocalizations and male copulatory behavior in castrated male deer mice (Peromyscus maniculatus bairdi).

The influence of testosterone (T), a 5 alpha-reduced metabolite of T, dihydrotestosterone, and an aromatized metabolite of T, estradiol, on 35-kHz ultrasonic calling and male copulatory behavior by male deer mice (Peromyscus maniculatus bairdi) was examined. Daily treatment with testosterone propionate (TP), dihydrotestosterone propionate (DHTP), or estradiol benzoate (EB) restored male ultrasonic calling in long-term castrated males. Both TP and DHTP restored male copulatory behavior, but EB was ineffective in facilitating copulation. Synergism of EB and DHTP action was observed; when subthreshold doses of EB (1 microgram/day) and DHTP (50 micrograms/day) were administered in combination, male ultrasonic calling and male copulatory behavior were activated. In relation to other comparative findings, these results indicate that the degree to which male sexual behavior is facilitated by 5 alpha-reduced androgens and/or estrogens is influenced by the species and the particular pattern of masculine behavior under consideration.

Animals↗
PubMed1970

The effect of thyroactive substances on the induction of cervico-vaginal and vulval tumours in castrate rats at various levels of carcinogenic treatment.

Medication with L-thyroxine or methylthiouracil of castrate rats painted weekly 5, 10, 20 or 40 times with DMBA does not alter the order of thresholds for carcinogenesis which increases from that for cervico-vaginal epitheliomas via squamous celled and basal celled vulval tumours to cervicovaginal sarcomas. Methylthiouracil lowers the threshold for basal celled vulval neoplasms.Sarcomas reach a peak of 25% with 20 doses of DMBA in non-medicated rats, but rise to 90% and at a faster rate in animals given either of the thyroactive drugs with further carcinogenic treatment.The optimal dose phenomenon for cervico-vaginal epitheliomas, i.e. a significant fall with continued painting from a peak reached by 5 to 20 doses of DMBA, is not affected by medication with methylthiouracil or L-thyroxine.Thyroactive compounds accelerate the formation of squamous celled vulval tumours which reach a maximum with 20 DMBA paintings; the total incidence as well as the proportion of carcinomas to papillomas falls with further treatment.Methylthiouracil promotes formation of basal celled vulval tumours at low dose levels, but inhibits it at the highest. In medicated as in non-medicated rats the induction of basal celled tumours of the vulva follows an optimum dose pattern.The optimal dose phenomenon and the effect of thyroactive compounds on the tissue-specific sensitivity to carcinogens are discussed.

Animals↗
PubMed2026

Super enhancer-driven transcriptional reprogramming promotes abiraterone resistance via neuroendocrine transition and ferroptosis evasion in castration-resistant prostate cancer.

Abiraterone resistance represents a major clinical challenge in the management of castration-resistant prostate cancer (CRPC), yet the epigenetic mechanisms that sustain this resistance remain poorly understood. In particular, how super enhancers (SEs) reprogram transcriptional networks to promote this therapy resistance has not been fully elucidated. Here, by integrating chromatin immunoprecipitation sequencing and transcriptome profiling, we identified aberrantly activated oncogenic SEs that drive the transcriptional upregulation of the transcription factors ELF3 and JUNB in abiraterone-resistance CRPC cells. Importantly, SE-driven activation of the ELF3/JUNB axis promotes abiraterone resistance by inducing WNT11-mediated neuroendocrine transition. In parallel, this transdifferentiated state is closely associated with ferroptosis resistance, as evidenced by the upregulation of key ferroptosis-protective genes, including FTH1 and GPX4. In contrast, disruption of the ELF3/JUNB-WNT11 axis markedly restored abiraterone sensitivity and triggered ferroptotic cell death in CRPC cells both in vitro and in vivo. Collectively, our findings highlight targeting SE-driven transcriptional programs as a promising strategy for overcoming abiraterone resistance in CRPC.

Male↗