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Afferent activity in the superior spermatic nerve of lambs--the effects of application of rubber castration rings.

Electrophysiological techniques were used to record afferent activity in the superior spermatic nerves of young lambs under general anaesthesia. Receptive fields were identified in the pampiniform plexus and the deep tissue of the testis in response to mechanical stimulation. Application of a standard rubber castration ring to the scrotal neck evoked vigorous afferent activity, including some from formerly silent units with receptive fields particularly in the pampiniform plexus. Some of this multi-unit discharge adapted rapidly within 10 s of the application of the ring and was followed by a discharge pattern which decayed exponentially over 90 min. The rate of decay of this discharge showed more than one exponent (time constant) with inflections at approximately 90 s and 16 min. After the application of the castration ring, quantitatively controlled scrotal compression continued to excite receptors, though a declining frequency was recorded over the period of observation. It was concluded that: (a) rubber castration rings initiated afferent activity which persisted for periods in excess of 90 min, a time course which is similar to the behavioural and humoral changes in the conscious animal; (b) both standard and small rubber castration rings were ineffective in rapidly producing neuronal pressure block of the slowly conducting afferent fibres in the superior spermatic nerve; (c) intra-testicular injection of local anaesthetic rapidly blocked afferent fibres running in the superior spermatic nerve.

Animals↗

Effect of steroid hormones and antihormones on hypothalamic beta-endorphin concentrations in intact and castrated female rats.

The aim of the present study was to evaluate the effects of estrogens and androgens on hypothalamic beta-endorphin (beta-EP) concentrations. Intact or castrated female rats were chronically (2 weeks) treated with estrogen (estradiol benzoate) and/or antiestrogens (clomiphene, cyclophenil or epimestrol), and with androgens (dihydrotestosterone or dehydroepiandrosterone sulphate) and/or antiandrogen (cyproterone acetate). A group of rats treated with vehicle were studied as comparison. The beta-EP concentrations were measured by radioimmunoassay on acidic extracts of rat hypothalami. The administration of clomiphene and cyclophenil significantly reduced hypothalamic beta-EP concentrations in intact rats, while both drugs or estradiol benzoate increased the peptide concentration in castrated rats. Both intact and castrated rats treated with epimestrol showed hypothalamic beta-EP concentrations higher than vehicle treated rats. The estradiol-induced increase of beta-EP was not changed by the concomitant administration of antiestrogens. The administration of dihydrotestosterone significantly decreased beta-EP concentrations in both intact and castrated female rats, while the treatment with dehydroepiandrosterone sulphate only slightly decreased beta-EP levels in intact female rats. The cyproterone acetate-chronically treated rats showed higher beta-EP concentrations than vehicle-treated rats and these changes were reversed by the concomitant addition of dihydrotestosterone or dehydroepiandrosterone sulphate. These results showed that estrogens play a positive role while androgens negatively influence the hypothalamic beta-EP concentrations in female rats, supporting the view that central beta-EP might be a target of gonadal steroid feedback signals.

Androgen Antagonists↗

The non-steroidal antiandrogen, bicalutamide ('Casodex'), may preserve bone mineral density as compared with castration: results of a preliminary study.

The impact of bicalutamide (Casodex) monotherapy on bone mineral density (BMD) was investigated in patients with locally advanced prostate cancer. BMD was assessed after treatment with bicalutamide 150 mg daily ( n=21) or by medical castration (goserelin acetate 3.6 mg every 28 days) ( n=8) for a median of 287 weeks. In 38% of castration compared with 17% of bicalutamide patients, femoral neck Z-scores were < or =-1 SD of the reference value (accepted as a two to three times increased risk of fracture) and T-scores were < or =-2.5 SD (World Health Organization definition of osteoporosis in white females). Total hip Z-scores were < or =-1 in 43% of castration patients and 13% of bicalutamide patients. In 38% of patients, lumbar spine BMD was affected by degenerative disease. These preliminary data suggest that there may be an advantage in terms of BMD in using bicalutamide monotherapy compared with castration; a benefit confirmed in a recent prospective randomised study.

Aged↗

Castration increases [125I]MK801 binding in the hippocampus of male rats.

This study examines the effect of castration and androgen replacement on [125I]MK801 binding in the hippocampus. In castrated male rats, [125I]MK801 binding was significantly increased in both the stratum oriens and radiatum and the pyramidal cell layer of CA1. In contrast, no increase in [125I]MK801 binding was observed in the stratum oriens and radiatum of CA1 of castrated rats that were treated with dihydrotestosterone. No change in [125I]MK801 binding was observed in the CA3 region or dentate gyrus after castration. The observed increase in [125I]MK801 binding in pyramidal cell neurons within CA1 suggests that androgens may potentially affect hippocampal function by modulating pyramidal cell NMDA receptors.

Androgens↗

Age and castration modulate the inhibitory action of neuropeptide Y on neurotransmission in the rat vas deferens.

The potency of neuropeptide Y (NPY) to inhibit the electrically induced contractions of the epididymal half of the vas deferens diminishes markedly with age, being at least 20 times lower in the adult than in the 26-day-old rat. Castration sensitizes the epididymal segment to NPY in a testosterone-reversible manner. [Pro34]NPY was 3 times less potent than NPY in prepubertal rats and inactive in castrated adults, while NPY-(13-36) had no effect in either group. In the prostatic half, NPY and its analogs were active in rats from all ages studied; the order of potency being NPY greater than [Pro34]NPY greater than NPY-(13-36). The sensitivity of the prostatic segment from adult rats to NPY was unchanged by castration or testosterone replacement therapy. The NPY content of the ductus increases during development being higher in the prostatic than in the epididymal half at all ages studied. Castration decreases the peptide content in the two segments and the effect is prevented by testosterone administration. The present investigation demonstrated that the effect of NPY on vas deferens neurotransmission is subject to regulation by sex steroids, which affects differently the response of the two segments of the ductus.

Aging↗

Effects of castration on volumes of the preoptic nucleus and the amygdala and on immunoreactivity of LH-RH fibers in the brain of the toad, Bufo japonicus.

We examined the influence of castration on the volumes of sexually dimorphic nuclei, the amygdala pars medialis (Am) and lateralis (Al), and the anterior part of the preoptic nucleus, and on the immunoreactivity of luteinizing hormone-releasing hormone (LH-RH) in brains of Japanese toads captured in spring and autumn. Animals were castrated (GnX) and half were implanted with testosterone (T) (GnX + T) and then killed and dissected after 1 month. Compared with sham-operated (Sham) toads, plasma androgen levels in autumn toads were significantly decreased by the castration, and those in both spring and autumn GnX toads were significantly elevated by the T implantation. The volume of Am in autumn toads was significantly reduced by GnX. Although not significant, changes in the volumes of the other nuclei, except for Al in spring toads, showed the following tendency 30 days after the operation: GnX + T greater than Sham greater than GnX. GnX did not alter LH-RH immunoreactivity in the median eminence. However, dense immunoreactive LH-RH fibers were found in the mesencephalic tegmental region in spring GnX toads but not in the other operation groups in both spring and autumn. LH-RH immunoreactivity was not altered in autumn toads. In spring GnX toads, thumb pads degenerated and evoked release calling was infrequent. These results suggest that (i) the volumes of sexually dimorphic nuclei, especially Am in the autumn toad, are androgen-dependent, and (ii) castration can modulate activity of the extrahypothalamic LH-RH-ergic projection in toad brain.

Amygdala↗

Absence of an effect of naloxone, an opioid antagonist, on luteinizing hormone release in vivo and luteinizing hormone-releasing hormone I release in vitro in intact, castrated, and food restricted cockerels.

The possibility that the tonic secretion of luteinizing hormone (LH) and chicken luteinizing hormone-releasing hormone I (LHRH-I) is regulated by an inhibitory action of endogenous opioid peptides was investigated in cockerels using the opiate receptor antagonist, naloxone. Baseline concentrations of plasma LH in the experimental cockerels were increased by surgical castration or reduced by limiting food intake. Baseline and K(+)-induced releases of LHRH-I from perifused mediobasal-preoptic hypothalami from castrated cockerels were higher than those from hypothalami from intact cockerels. Similarly, baseline and K(+)-induced releases of LHRH-I from perifused mediobasal hypothalami from fully fed cockerels were higher than those from the hypothalami from fasting cockerels. Intravenous injections of 0.1, 1, or 10 mg naloxone/kg body weight failed to increase the concentration of plasma LH in castrated, intact, fully fed, or fasted cockerels. Perifusion of mediobasal-preoptic hypothalami from castrated or intact cockerels with 200 microM naloxone or mediobasal hypothalami from fully fed or fasted cockerels with 10 microM naloxone failed to stimulate the release of LHRH-I. These observations suggest in the cockerel that endogenous opioid peptides may not play an obligatory role in the inhibitory control of the tonic secretion of luteinizing hormone.

Animals↗

Induction of copulatory behavior in castrated female and male Arctic foxes.

The aim of the study was to test if it is possible to induce complete copulatory behavior in castrated Arctic foxes (Alopex lagopus) of both sexes for the purpose of other experiments. Two groups of castrated, sexually experienced Arctic foxes, four pairs in Experiment 1 (a pilot study) and eight pairs in Experiment 2, were treated with different regimes of hormone (estrogens and progesterone in females, testosterone in males). The animals were than tested for copulatory behavior. Nine out of 12 castrated bitches and 10 out of 12 castrated males displayed copulatory behavior during the season of reproductive quiescence for intact Arctic foxes. All the treatments induced complete copulatory behavior (i.e., copulation leading to locking) at least in some animals of both sexes. Examination of results for individual animals suggested that copulatory performance was influenced by preference for specific partners. Also the occurrence of copulation in an early test facilitated its reoccurrence on a later test in the same day with a different partner.

Animals↗

Erectile function and bulbospongiosus EMG activity in estrogen-maintained castrated rats vary with behavioral context.

Electromyographic (EMG) activity in the bulbospongiosus muscles (BS) was recorded to monitor potential castration-induced alterations in muscle activity during copulation and reflexive erections. EMG recordings were made from intact male rats and from castrated rats maintained from 7 to 50 days on estradiol benzoate (300 micrograms/day) or testosterone (200 micrograms/day). Despite a 40-50% postcastration reduction in the weight of the BS and accessory sexual glands in estrogen-treated rats, the pattern of EMG activity during copulation was similar across groups. In estradiol-treated males, the EMG burst frequency during mounts and burst duration during intromissions exceeded the parameters of intact males and of castrated males maintained on testosterone. Between intromissions, and following ejaculatory patterns, estrogen-treated males displayed spontaneous muscle bursts accompanied by visually confirmed erection of the glans penis, but these males quickly lost the capacity for reflexive erections. These data demonstrate that despite castration-induced atrophy of the penile muscles and, presumably, their spinal motor nuclei, the motor output to these muscles is maintained following androgen removal. The capacity for substantial penile erection is retained during copulation long after reflexive erections have diminished.

Androgens↗

Influence of castration and androgen treatment on the synthesis of prostatic binding protein and the concentration of its mRNA in the rat ventral prostate.

The regulation by androgens of the synthesis of prostatic binding protein (PBP), an abundant secretory protein of the rat ventral prostate, was studied by measuring the rate of incorporation of [3H]leucine into total protein and into PBP by prostatic tissue in vitro. PBP-specific synthesis dropped to 30% of the intact level after 3 days and to 5.5% after 7 days. Administration of androgens to 7 day-castrated rats reversed these changes: 36% of the control value was reached after 3 days of treatment and 70% after 5 days. The mRNAs of PBP were measured under similar conditions by means of dot hybridization, using C1-, C2- and C3-specific cDNA-clones. The 3 mRNAs followed a parallel course. They decreased to about 18% on the third day after castration and to about 2% after 7 days. Androgen treatment of 7-day castrated rats produced a small increase of these levels after 1 day. After 3 days 15% of the intact level was reached. The general similarity of the time course of PBP synthesis and PBP mRNA levels in castrated and androgen treated rats supports a transcriptional regulation mechanism, although there also is some evidence for an influence on protein synthesis in general.

Androgen-Binding Protein↗

Studies on the effects of dehydroepiandrosterone and its metabolites on attack by castrated mice on lactating intruders.

Triads of castrated male mice (residents) were injected each day for 2 weeks with oil vehicle or 280 nmol of dehydroepiandrosterone (D). They were tested for their attack on a lactating female (intruder) introduced in their home-cage 2,24 or 48 hr after their last injection. D significantly reduced male aggressive behavior for at least 24 hr. Other groups of castrated males were injected each day with vehicle or 280 nmol of D, dehydroepiandrosterone sulfate (DS) or androstenediol (ADIOL). D, but neither DS nor ADIOL, significantly reduced their aggressive responses to intruders. Neural levels of D, DS and testosterone (T) were measured in intact males injected with vehicle or D. The concentration of D in brain was unchanged by castration and was increased about 20 fold in D injected males. The concentration of neural T was 10 nmol/g of tissue in intact males, was almost undetectable in castrated males, and was slightly increased in D injected males. Further work will be needed to identify the steroid molecule(s) responsible for this behavioral effect of D.

Aggression↗

Sexual interactions between estrous female rats and castrated male rats treated with testosterone propionate or estradiol benzoate.

Estrous female rats display 'precopulatory behaviors' such as ear wiggling and hopping/darting when castrated males treated with testosterone propionate (TP) are placed in their vicinity and before copulatory interactions have taken place. Castrated males treated with estradiol benzoate (EB) do not elicit these precopulatory behaviors in advance of copulatory interactions. It therefore seemed of interest to study females' sexual behavior with castrated males treated with TP or EB when males or females had primary control over the temporal patterning of the behavior. Unrestrained sexual behavior (= male control) with EB-treated males was characterized by large numbers of intromissions and long periods of time preceding ejaculation, as compared with interactions with TP-treated males. The temporal pattern of sexual behavior did not change importantly when the males were tethered (= sexual behavior controlled by females). When given a choice between two sexually active castrated and tethered males, one treated with TP and the other with EB, estrous females 'preferred' EB-treated animals in various respects. Fewer interactions occurred with, and less time was spent in the vicinity of, TP-treated males over prolonged observation periods (115-135 min). The preference for EB-treated males disappeared, and TP- and EB-treated animals became equally attractive, when the vaginal opening of the female animals was covered with adhesive tape to prevent the occurrence of penile intromissions during mounting. It is concluded that female control over copulatory behavior does not necessarily change the females' sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dissociation of androgen-dependent sociosexual behaviors in response to castration in Long-Evans rats.

Copulatory behavior and associated social behaviors such as ultrasonic vocalizations and scent marking are reduced in frequency following castration and are restored by exogenous administration of androgens. In the present study, we report the behavior of a subgroup of male Long-Evans rats in which there was a dissociation between the responses of androgen-dependent behaviors to castration. Five weeks after castration, 52% of the males tested (13 of 25) had higher 50 kHz vocalization frequencies than during precastration tests. This group continued to emit vocalizations after castration and actually increased their number of vocalizations over postcastration tests (pretest: 34.5 +/- 4.8 to week 15: 62.8 +/- 10.9/10 min test). The remaining males (n = 12) exhibited a decline in vocalizations (pretest: 29.7 +/- 5.1 to week 15: 6.5 +/- 2.7) that we typically observe in our laboratory. Both groups showed the expected decline in scent-marking frequency over the postcastration tests and were impaired in performance of copulatory behavior. Seminal vesicle and adrenal gland weights did not differ between the two groups. The 25 males were of the same genetic strain as previous animals in our laboratory except that they were born and raised in a different location prior to shipment to our laboratory. Androgens, therefore, may be only one of the possible influences mediating ultrasonic vocalizations.

Androgens↗

Twenty-four hour felinine [corrected] excretion patterns in entire and castrated cats.

The purpose of this study was to determine the 24 h urinary excretion of a sulphur containing amino acid called felinine in entire and castrated cats of both sexes. Entire male cats excreted (mean +/- SEM) 122 +/- 23.6 mmol of felinine per kg bodyweight per day with castrated males, entire females and spayed females excreting 41 +/- 8.4, 36 +/- 7.3 and 20 +/- 3.8 mmol, respectively. There was an overall significant difference between groups in the amounts of felinine excreted in 24 h [F(3, 24) = 11.8, p < 0.0001] with there being significant differences between entire males and castrated males (p < 0.001) and castrated males and spayed females (p < 0.05). There was no difference in excretion between entire and spayed females. Urine volumes were not significantly different for the 24 h period. The differences in excretion levels were caused by different concentrations of felinine in the urine with entire male cats excreting (mean +/- SEM) 2.0 +/- 0.55 g of felinine per litre of urine. The data obtained in the present study support the concept that felinine, which has been found in Felidae species only, may be testosterone dependent. Felinine may be involved in territorial marking.

Amino Acids, Sulfur↗

Testosterone 5 alpha-reductase in discrete hypothalamic nuclear areas in the rat: effect of castration.

The conversion of testosterone into 5 alpha-dihydrotestosterone (DHT) has been studied in different hypothalamic nuclear areas and in the superficial layers of the cerebral cortex of normal and castrated male rats. The tissue fragments utilized in each incubation have been punched from frozen brain sections utilizing calibrated needles. Castration has been performed 12 (short term) and 180 (long term) days before sacrifice. The nuclear areas studied include: the medial preoptic nucleus (MPN), the lateral preoptic nucleus (LPN), the anterior hypothalamic nucleus (AHN), the lateral hypothalamic nucleus (LHN), the posterior hypothalamic nucleus (PHN), the nucleus ventromedialis (HVM), the arcuate nucleus (AR), the median eminence (ME), the nucleus paraventricularis (HPV), the supraoptic nucleus (SO) and the suprachiasmatic nucleus (SC). The possible effect of castration on the 5 alpha-reductase, were assessed in the MPN,LPN,AHN,LHN,PHN and in the cerebral cortex. The results indicate that, in the male rat: 1) the lateral preoptic(LPN) and the lateral hypothalamic nuclei(LHN) possess a 5 alpha-reductase activity higher than that present in the cerebral cortex and in the other hypothalamic nuclei considered; 2)the suprachiasmatic nucleus (SC) apparently possesses a testosterone metabolizing activity lower than that found in any other nervous structures studied so far; 3) castration does not seem to influence the 5 alpha-reductase activity either in the hypothalamic nuclear structures considered or in the cerebral cortex.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Synergistic effect of testosterone and of a luteinizing hormone-releasing hormone agonist on androgen receptor content in the ventral prostate of castrated rats.

The aim of the present experiment was that of studying the effect of an LHRH agonist analog on the prostatic content of cytosol and nuclear salt-extractable and salt-resistant androgen receptors (AR). Castrated rats were treated for six days with the LHRH agonist WY 40972 (A), with testosterone enanthate (T) or with A plus T. Intact adult male rats and castrated rats treated with the vehicle served as controls. The animals were sacrificed 18 h after the last subcutaneous injection. The ventral prostates were quickly removed and submitted to subcellular fractionation for the determination of cytosol and nuclear AR content. In addition, the weights of the prostates and of the seminal vesicles were recorded, and serum levels of LH and FSH were evaluated by radioimmunoassay. The dissociation constants (Kd) of cytosol and nuclear AR, on the order of 1 x 10(-9) M, were not affected by the various treatments. Conversely, the combined treatment with T and A induced a significant increase of nuclear AR in the prostatic tissue, when compared to the levels found in castrated rats treated with T alone and in intact rats. The treatment with T was able to restore the reproductive organs to their normal weights. The treatment with A inhibited the hypersecretion of gonadotropins induced by castration. The results show that, under the conditions of the present experiment, A exhibits a synergistic effect with T on nuclear AR content in the rat ventral prostate. The results also suggest that A acts directly on this androgen-dependent structure.

Animals↗

Systemic or intracranial apomorphine increases copulation in long-term castrated male rats.

Testosterone or its estrogenic metabolite is thought to be necessary to activate male rat sexual behavior. However, systemic injections of dopamine agonists, alone or in combination with exogenous testosterone, can partially restore copulatory behavior during the prolonged period of its postcastration decline. The present experiments tested the ability of the dopamine agonist apomorphine, injected systemically or into the medial preoptic area (MPOA), to restore copulation in long-term castrates that had failed to copulate on two successive weekly tests. In Experiment 1, systemic injections of apomorphine increased the number of mounts and intromissions in castrated males, compared to vehicle. In castrates given subthreshold testosterone propionate (TP), apomorphine increased the number of mounts. In Experiment 2, microinjections of apomorphine into the MPOA increased the number of mounts in animals without TP. Subthreshold TP had no significant effects in either experiment, either alone or interacting with apomorphine. These results suggest that stimulation of dopamine receptors can partially restore copulation, even after its virtual elimination. Furthermore, dopamine receptors in the MPOA may contribute to sexual arousal in long-term castrates.

Animals↗

L-dopa reverses castration-induced disruption of dishabituation responses to female chemical cues in male rats.

In the present experiment, habituation/dishabituation behavioral tests were conducted to measure discriminatory olfactory recognition responses to chemical cues among control, castrated, and castrated+L-3,4-dihydroxyphenylalanine (L-DOPA)-treated male rats. Castration produced a disruption of dishabituation responses to female urine, and this effect was reversed by treatment with L-DOPA. In the posterior olfactory bulb, 3,4-dihydroxyphenlacetic acid (DOPAC) levels were significantly increased in L-DOPA-treated animals compared with the vehicle-treated control and castrated groups. No significant differences in olfactory bulb norepinephrine or dopamine concentrations among the three treatment groups were obtained. The restoration of behavioral dishabituation responses following L-DOPA treatment suggests that the catecholaminergic system of the olfactory bulb may play a critical role in the recognition and possibly attractions for or preferences to female chemical cues.

3,4-Dihydroxyphenylacetic Acid↗