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Differential effect of castration on the somal size of pudendal motoneurons in the adult male rat.

We have examined the organization of the androgen sensitivity of pudendal motoneurons in adult male rats. Comparisons of mean somal cross sectional area of pudendal motoneurons identified by retrograde labeling with horseradish peroxidase were made between three treatment groups: castrates with testosterone propionate supplementation, castrates with placebo, and sham castrates. Bulbospongiosus and ischiocavernosus motoneurons were sensitive to androgen treatment, whereas external anal sphincter and external urethral sphincter motoneurons were not.

Animals↗

Testosterone prevents castration-induced reduction in peripheral benzodiazepine receptors in Cowper's gland and adrenal.

The effect of surgical castration of adult male Sprague-Dawley rats on peripheral and central benzodiazepine (BZ) receptors was studied. Following removal of the testes, a significant decrease in the density of peripheral BZ receptors (PBR) was observed in Cowper's glands (71%; P less than 0.005) and the adrenal (31%; P less than 0.01), but not in the heart. Administration of testosterone acetate (TA) prevented castration-induced PBR depletion. Orchiectomy per se, as well as TA administration to castrated rats, had no effect on central or peripheral BZ receptors in whole brain without the cerebellum. These results indicate the regulatory role of testosterone in the regulation of PBR in Cowper's glands and adrenal.

Adrenal Glands↗

Androgen receptor immunoreactivity in intact and castrate guinea pig using antipeptide antibodies.

We developed and used antibodies to an androgen receptor (AR)-specific synthetic peptide (amino acids 201-222 of the human androgen receptor) to localize AR in the brain and peripheral tissues of intact and castrate adult male guinea pigs. Immunoreactivity was localized to the nucleus of epithelial and stromal cells in the prostate of intact animals. Immunostaining was abolished in the prostate 4 days following castration. Androgen receptor immunoreactivity was found in brain nuclei known to be involved in reproductive and other androgen-dependent behaviors, including the preoptic area, medial basal hypothalamus, and anterior pituitary gland. Castration had no effect on the distribution or intensity of AR immunostaining in the brain. These data indicate a differential regulation of AR in the brain compared to peripheral tissues.

Amino Acid Sequence↗

Androgen receptor-like immunoreactivity in the Brazilian opossum brain and pituitary: distribution and effects of castration and testosterone replacement in the adult male.

Androgens are involved in a variety of centrally mediated functions after binding to their intracellular receptors. In the present report, we have employed the androgen receptor antibody, PG-21, and indirect immunohistochemistry to examine the distribution of cells containing androgen receptor-like immunoreactivity (AR-IR) in the intact adult male Brazilian opossum brain and pituitary. Additional adult males were castrated to examine the effects of withdrawal of circulating androgens and testosterone replacement on AR-IR. Immunoblots and immunohistochemical controls demonstrated that the androgen receptor in the opossum brain and peripheral tissues are of a similar molecular mass as to has been reported for the rat. Cells containing AR-IR were widely distributed throughout the brain of intact adult males. The highest number of immunoreactive cells were present in the dorsal and ventral nuclei of the lateral septum, medial division of the bed nucleus of the stria terminalis, medial preoptic area, median preoptic nucleus, nucleus of the lateral olfactory tubercle, central amygdaloid nucleus, anterior cortical amygdaloid nucleus, posterior amygdaloid nucleus, subiculum, ventromedial hypothalamic nucleus, arcuate-median eminence region, and ventral premammillary nucleus. The anterior pituitary gland also contained a high number of cells containing AR-IR. The general distribution of AR-IR both in the brain and anterior pituitary gland resembled that reported for other mammalian species. Castration of the adult males four days prior to perfusion eliminated androgen receptor immunostaining throughout the brain except for a few lightly immunostained cells in the ventral nucleus of the lateral septum and stria terminalis. Androgen receptor immunostaining was decreased in the anterior pituitary gland following castration and became cytoplasmic. Testosterone administration 2 h before perfusion restored AR-IR both in the brain and anterior pituitary gland. These data suggested that immunohistochemical detection of bound (nuclear) androgen receptors as seen with PG-21 antibody in the brain and anterior pituitary gland of the opossum is dependent upon circulating androgens. Further, the wide distribution and similarity in localization of androgen receptors in the opossum brain and anterior pituitary gland to that of other species suggests that androgen receptors might be involved in similar functions in the opossum as has been reported for other species.

Animals↗

Effect of two new androgen esters on serum levels of testosterone in castrated rhesus monkey.

The pharmacokinetics of two new androgen esters were tested in castrated male rhesus monkeys. A single injection of 40 mg of 20 Aet-2 (testosterone-trans-4-n-pentyl cyclohexyl carboxylate) increased serum testosterone to three times the castrate levels and was maintained nearly at this level until day 182. When given as four separate injections of 20 mg each, 20 Aet-2 increased serum testosterone within 24 hours and the peak levels were attained on day 2 (34.6 +/- 6.20 nmol/L) which was more than five times the levels obtained by 40 mg 20 Aet-2 given as a single injection. This was followed by a decrease in serum testosterone until day 98 when the levels were similar to that in animals given a single injection of 20 Aet-2. Administration of 40 mg of 3 Ad (testosterone-cis-3-(n-hexyl) cyclobutane carboxylate) given as a single injection increased serum testosterone levels to reach a peak level (47.4 +/- 4.64 nmol/L) on day 5 followed by a gradual decrease to castrate levels by day 70. The profile of serum testosterone in animals injected with 80 mg of 3 Ad as four separate injections was similar to that in animals given a single dose of 40 mg of 3 Ad. The data suggest a correlation between the bioavailability of the drug and the formulation of the vehicle. The possible effect of hydrolysis rate on pharmacokinetics of the drugs is discussed.

Animals↗

Serotonin involvement in the inhibition of luteinizing hormone (LH) release induced by prostaglandin D2 (PGD2) in castrated male rats.

p-Chlorophenylalanine (PCPA, 320 mg/kg i.p.), an inhibitor of serotonin (5-HT) synthesis, and 5,6-dihydroxy-tryptamine (5,6-DHT, 50 micrograms i.c.v.), a drug toxic to the indoleaminergic system were used to test the involvement of 5-HT in the mediation of the inhibitory effect of prostaglandin D2 (PGD2) on luteinizing hormone (LH) release in castrated male rats. The i.c.v. administration of PGD2 suppressed the episodic LH release characteristic of castrated rats and decreased mean plasma LH levels and mean LH pulse amplitude significantly. Pretreatment with PCPA or 5,6-DHT apparently eliminated the inhibitory effect of PGD2 on LH secretion. These results suggest the possible involvement of a serotonergic mechanism in the mediation of the suppression of LH secretion induced by PGD2 in castrated male rats.

5,6-Dihydroxytryptamine↗

Estrogen induction of progestophilins in rat estrogen-sensitive cells grown in media supplemented with sera from castrated rats and from rats bearing an alpha-fetoprotein-secreting hepatoma.

The purpose of this work was to study the effect of alpha-fetoprotein (AFP) over cell multiplication and the induction of an estradiol-17 beta (E2)-dependent marker, i.e., progestophilins in E-sensitive cells C2(9)RAP derived from a W/Fu rat pituitary tumor. These cells proliferate in isogeneic hosts under the influence of E2, while they proliferate in culture regardless of the presence of E2. C2(9)RAP cells were grown in medium supplemented with 10% horse serum. Progestophilin levels were measured 48 h after adding serum (20% horse, or castrated rat, or AFP-secreting tumor-bearing rat) and estrogen to the 10% horse serum-supplemented medium in which the cells were growing. Maximal induction of progestophilins was obtained at 3 X 10(-10) M E2 in cells grown in medium containing horse or castrated rat serum. In contrast, maximal induction of progestophilins required 3 X 10(-8) M E2 in cells grown in medium supplemented with the serum of Morris hepatoma 7777-bearing rats. This serum contained AFP levels comparable to those present at birth in the rat. 11-Methoxy-17 beta ethynylestradiol (R2858), a synthetic estrogen with little affinity for AFP, was also tested for its ability to induce progestophilins. The degree of maximal induction of progestophilins expressed as percentage of the respective control, was similar for all experimental groups, both with E2 and with R2858. In addition, we compared the free E2 levels in the culture medium with the progestophilin levels and the cell proliferation rate. We found that the progestophilin levels were maximal at free E2 concentrations above 11 pg E2/ml, whereas there was no correlation between the free E2 levels and the proliferation rate. Moreover, the proliferation rate of cells in medium supplemented with horse or castrated rat serum was maximal at concentrations of free E2 below 0.4 pg/ml; whereas cell proliferation was inhibited with hepatoma serum even at concentrations of free E2 of 44 pg/ml. We conclude that the effect of hepatoma serum on the E2 induction of progestophilins seems to be mediated by the effect of AFP on the availability of free estrogen, since it is abolished by the addition of both natural and synthetic estrogens. The inhibitory effect of hepatoma serum upon cell proliferation is not reversed by estrogens and thus seems to be mediated by mechanisms other than E2 trapping by AFP.

Animals↗

Testosterone control of territorial behavior: tonic-release implants fully restore seasonal and short-term aggressive responses in free-living castrated lizards.

Two aspects of hormonal control of aggressive territorial behavior in male mountain spiny lizards Sceloporus jarrovi were studied. First, testosterone (T) implants were given to free-living castrated males during the breeding season. These implants fully restored breeding season levels of aggressive and sexual behavior. Earlier studies showed that identical implants given to free-living males during the nonbreeding season did not induce full breeding season levels of aggression. The full effectiveness of these implants during the breeding season indicates that the lack of effectiveness in the nonbreeding season was not due (1) to the need to replace additional gonadal factors or (2) to ineffectiveness of tonic delivery by the implants. It is more likely that males are less sensitive to T during the nonbreeding season or that other cues present in the breeding season environment synergize with T to induce full levels of aggression. Thus, seasonal changes in aggressive behavior in male S. jarrovi cannot be explained simply as a direct response to changes in circulating levels of T; other environmental factors play a necessary role as well. In the second phase of the study, changes in aggressive behavior of free-living T-implanted castrates were monitored following staged encounters with other males. Despite their inability to alter secretion rates of T, the T-implanted castrates still showed a rapid postencounter increase in aggressive displays that was identical to controls. Previous results showed that this dramatic postencounter increase in aggressive behavior is not accompanied by simultaneous changes in circulating T. Together, these results now allow the hypothesis that this rapid behavioral change in aggressive behavior is caused by simultaneous changes in circulating T levels to be confidently rejected.

Aggression↗

Effects of castration and androgen treatment on aromatase activity in the brain of mature male Atlantic salmon (Salmo salar L.) parr.

Brain homogenates from male Atlantic salmon parr aromatized tritiated androstenedione to estrogens. The aromatase activity in homogenates of whole brains from castrated male parr was lower than that in homogenates from sham-operated male parr in autumn. This was also found in homogenates of the telencephalon and diencephalon, but not in homogenates of the tectum opticum. Treatment of castrated males with testosterone (T) and 11-ketoandrostenedione (OA) increased the aromatase activity in whole brains. T, but not OA, also significantly increased aromatase activity in all brain parts. In spring, half a year after the peak breeding period, mature parr males had a lower aromatase activity in telencephalon, diencephalon and tectum than that found in castrated males in autumn, whereas immature males displayed an even lower level of activity.

Androgens↗

Partner preference behavior of estrous female rats affected by castration of tethered male incentives.

Estrous female rats were allowed to interact with either of two tethered intact male rats or to stay in an empty middle part of a three-compartment observation cage during a 60-min test. Sexual interactions occurred with both males (resulting in one to five ejaculations) but most time was spent in the empty compartment. After castration of one of the males, females spent more time with this male than with the intact male, although sexual interactions continued with both incentive animals. This "preference" for the castrated male persisted through the second hour of observation in a second experiment (total test time 115 min) although sexual interactions had virtually ceased during this period. Females' preference for castrated males seemed largely the consequence of aversion to genital stimulation received during intromissions by intact animals: (a) when intromissions were prevented through vaginal occlusion, intact males became by far the preferred partners for the whole 2-hr period of testing while sexual behavior continued to occur throughout the test; (b) when choice was allowed between a testosterone-treated ovariectomized female and an intact male, sexual interaction occurred with both tethered incentive rats but the female became the preferred animal. The results suggest that two opposite tendencies play a role in sexual motivation of estrous female rats: attraction resulting from the action of ovarian hormones on the central nervous system and rejection resulting from genital sensory stimulation through the male's genitalia.

Animals↗

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↗

Androstenedione therapy reinstates normal, not supernormal, song structure in castrated adult male zebra finches.

In previous studies, androstenedione (AE) replacement therapy restored the highest levels and intensities of courtship song displays in castrated male zebra finches of any hormone tested. Furthermore, female zebra finches responded strongly to AE-treated males and preferred intact males given small AE implants to unsupplemented males. In this study, we asked whether AE treatment might alter song structure, since male song is an important cue in mate choice by female zebra finches. Songs of adult males were recorded. The males were then castrated and given AE therapy and recorded again. No differences were found between the courtship or undirected songs males sang before castration and after AE treatment. As in previous studies, the structure of a male's courtship song differed significantly from his undirected song, and the structural differences between these two song types were not altered by AE treatment.

Androstenedione↗

Food conditioning, castration, testosterone administration and sexual behavior in the male rat.

Chronically food-deprived male rats, when paired with a female rat in heat, were rewarded by receiving a food pellet following each intromission. Following castration there was a rapid decline in all aspects of male sexual behavior: after 3 weeks all sex behavior had stopped. There were no differences between the conditioned males and their yoked controls. Substitution with two doses of testosterone (through silastic implants) restored sexual behavior, but equally so in the conditioned and the control animals. Removal of the testosterone implant again caused a very rapid decline in sexual behavior, no differences between experimental and yoked control males. These results suggest that food, as a non-sexual stimulus, does not cause hungry male rats to continue to copulate for prolonged periods following castration. Furthermore, the combination of chronic food deprivation plus castration do summate with each other in the very rapid decline and cessation of male sexual performance.

Animals↗

Restoration of the copulatory pelvic thrusting pattern in castrated male rats by the intracerebral implantation of androgen.

The characteristics of duration, vigour, frequency and rhythmicity of pelvic thrusting during copulation were studied by an accelerometric technique in 25 male rats before castration and following restoration of sexual behavior by local implants of testosterone propionate (TP) in the medial preoptic area (mPOA). Twenty-one Ss displayed the complete copulatory pattern during the control tests. Implantation of TP in the mPOA restored mounting activity after castration in 14 out of 21 Ss and only six of them "ejaculated." Spinal cord structures involved in pelvic thrusting of castrated Ss implanted with TP were presumably not exposed to circulating androgen since the sexual accessories were atrophic; in spite of this, only modest differences were found in the characteristics of pelvic thrusting, i.e., an increase in the duration of the mounting trains of the TP implanted Ss. Present data suggest that activation of mPOA-anterior hypothalamic neurons would not only affect limbic and cortical areas related to sexual arousal through their ascending connections but would also modulate through descending pathways, the activity of lower spinal structures involved in copulation.

Animals↗

Castration alters susceptibility of male rats to specific seizures.

Studies in female rats indicate that estrogen reduction has both pro- and anticonvulsant effects on seizures, but that the respective effects are limited to specific types of seizures at selected doses of picrotoxin. This study was conducted to see if testosterone reduction had parallel effects on seizure susceptibility in males. Male rats were given castration or sham operations and allowed 3 weeks to recover. The latencies to myoclonic, focal, akinetic, and generalized tonic-clonic (GTC) seizures were scored in independent groups of sham-operated or castrated males after injection with picrotoxin (3.5-7.5 mg/kg). The results showed that castrated males had significantly shorter latencies to GTC seizures than sham-operated males at the 3.5 mg/kg and 5.5 mg/kg doses of picrotoxin. There were no significant differences in the latencies to myoclonic, focal, or akinetic seizures between the two surgical groups. The findings suggest that, unlike endogenous estrogen, endogenous testosterone exerts only an anticonvulsant effect and that the effect is limited to GTC seizures.

Animals↗

Sexual and aggressive behaviour of adult male marmosets (Callithrix jacchus) castrated neonatally, prepubertally, or in adulthood.

During early postnatal development, males of some primate species exhibit higher levels of plasma testosterone than females. The possible significance of this for behavioural development was examined in male marmosets castrated neonatally (NC), prepubertally (PC), or in adulthood (AC) and reared in their natal groups. Age-matched intact (AI) adult males served as controls. All males were removed from their natal groups as adults for pair testing with unfamiliar conspecific males and females. NC males did not mount, but were frequently aggressive during tests with females. NC males also elicited aggression from females but rarely from intact males. PC and AC males attempted copulation during the majority of tests with females; less aggression occurred but more so in tests with PC males than between females and AC males. Aggression between PC or AC males and intact males was much more frequent than when NC males met intacts in paired encounters. Results show that secretion of testicular hormones during infancy in male marmosets has important effects upon the development of sexual and aggressive behaviour. Castration in infancy has measurably different effects upon behavioural development than castration performed later in life (prepubertally or in adulthood).

Aggression↗

Anabolic-androgenic steroids and aggression in castrated male rats.

The resident-intruder paradigm of aggression was utilized to evaluate the aggression-inducing properties of two anabolic-androgenic steroid (AAS) compounds, methyltestosterone and stanozolol, in castrated male rats. Three weekly tests were conducted. On test week three, castrated males treated with methyltestosterone displayed levels of aggression equivalent to the levels displayed by castrated males treated with testosterone propionate on most of the behavioral indices assessed. In contrast, treatment with stanozolol at the dose used in this study was completely ineffective in eliciting aggressive behavior. AAS effects on aggression were mirrored by their ability to stimulate seminal vesicle growth. There were no effects of AAS treatments on the levels of locomotor activity. These findings highlight the heterogeneity of AAS effects on the nervous system and behavior and indicate that the psychological effects reported by human AAS abusers may depend upon the distinct chemical structures of the abused steroids.

Aggression↗

Changes in plasma cortisol concentration in lambs of three ages after three methods of castration and tail docking.

Lambs were handled only or castrated and tail docked at five, 21 and 42 days of age by either surgery, rubber ring or rubber ring and Burdizzo. Plasma cortisol was measured in blood samples taken before and at 12, 24, 36, 48, 60, 72, 84, 96, 138 and 180 minutes after castration and docking. Pre-treatment and peak cortisol values were highest in five-day-old lambs. The peak cortisol values, at each age, were similar for surgery and rubber ring groups. However, the peak occurred earlier after surgery and rubber ring Burdizzo than after rubber ring only treatment. The cortisol peak was 28 nmol litre-1 lower after rubber ring Burdizzo than surgery or rubber ring only. Plasma cortisol returned to pretreatment values within 84 minutes after rubber ring Burdizzo, 96 to 138 minutes after rubber ring only but not within 180 minutes after surgery. The changes in plasma cortisol together with the changes in behaviour suggest that the rubber ring Burdizzo method of castration and docking of lambs at all ages, was probably the least painful of the methods tested.

Aging↗