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Strange-male-induced pregnancy disruption in mice: potentiation by administration of 17 beta-estradiol to castrated males.

Previous evidence suggests that androgen activity is necessary for strange males to disrupt early pregnancy in mice. Inseminated females were housed below castrated males, separated by a wire-mesh grid. Castrated males did not disrupt pregnancy, whereas those given daily injections of 27 or 81 micrograms of 17 beta-estradiol did so. In conjunction with previous evidence, these data suggest a similarity between the hormones involved in the capacity of males to disrupt pregnancy and the hormones directly implicated in the females' vulnerability to pregnancy disruption.

Animals↗

Castration affects the emission of an ultrasonic vocalization in a nocturnal primate, the grey mouse lemur (Microcebus murinus).

Male primates have evolved particular displays to advertise male fitness. In nocturnal prosimians it was assumed that such displays (vocal advertisement, marking behaviour) are hormonally dependent and influenced by olfactory cues of a receptive female. To test this assumption mouse lemur males of different gonadal status (males castrated as adults, normal males), or of varying olfactory input (males vomeronasalectomized or bulbectomized as adults) were paired with intact "stimulus" preoestrous females and vocalization, vocal rates, and marking behaviours were monitored. The vocal rate of only one particular vocalization, the "trill" advertisement call, was sexually dimorphic and changed depending on gonadal status. Vocalization rate declined significantly in sexually experienced, castrated males as did their marking behaviour. There was however no significant correlation between either calling rate or marking behaviour and plasma testosterone levels in gonadally intact males. Neither vomeronasalectomy nor bulbectomy had a significant effect on trill calling rate or marking behaviour. Results imply that testicular hormones have a greater impact on advertisement calling and marking motivation than olfactory information of preoestrous females. In contrast to rodents, ultrasonic calling rate seems to be not only dependent on gonadal status, but also on social experience.

Animals↗

Behavioural responses of lambs of three ages in the first three hours after three methods of castration and tail docking.

The behavioural responses of groups of seven lambs were compared with control groups after castration and tail docking by rubber rings, application of a Burdizzo clamp in addition to a rubber ring and after surgical castration at five, 21 and 42 days. All methods at all ages produced changes in behaviour which were interpreted as indicative of considerable pain. The rubber ring groups showed most changes in behaviour at all ages. The rubber ring with Burdizzo groups showed least changes and some lambs in these groups showed much less response than others. The surgical groups showed some behavioural responses which were different, both qualitatively and quantitatively to those in other groups. It is concluded that indices used for recognition and assessment of acute pain received conditional support, that modification of the rubber ring with Burdizzo may provide the least painful method without local anaesthesia and that age had little effect on the responses.

Animals↗

The 5 alpha-reductase activity of the subcortical white matter, the cerebral cortex, and the hypothalamus of the rat and of the mouse: possible sex differences and effect of castration.

Previous studies have shown that the central nervous system is able to convert testosterone into 17-beta-hydroxy-5-alpha-androstan-3-one (DHT), by the action of the enzyme 5-alpha-reductase. The data here presented show that, in the brain of the rat and the mouse of both sexes, the 5-alpha-reductase activity is more concentrated in the subcortical white matter than in the hypothalamus and in the cerebral cortex. The enzymatic activity is apparently higher in the rat than in the mouse brain. The formation of DHT in the subcortical white matter, in the hypothalamus and in the cerebral cortex of both rats and mice does not show any sexual difference. Moreover, in the rat no effect of short- or long-term castration or neonatal castration or testosterone replacement could be observed on the formation of DHT in the three brain structures considered (even in the subcortical white matter, the cerebral tissue more active in converting testosterone into DHT). The present data support the view that the 5-alpha-reductase present in the brain is not under androgenic control.

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

Structural requirements for the induction of "immunological castration" by linear monomeric LHRH-lys-MDP administered in saline.

It was previously shown that "castration" could be obtained in male mice by immunizing them in saline with a conjugate referred to as LHRH-Lys-MDP and containing the decapeptide hypothalamic hormone LHRH covalently linked to the adjuvant glycopeptide MDP-Lys. Since coupling was made using carbodiimide, it could have produced oligomers or isomers as well as monomers. In the present investigation male and female mice were immunized in saline with a linear monomeric MDP linked LHRH molecule obtained by total synthesis. Histological studies showed gonadal alterations in both male and female mice. The study of analogs provided a correlation between the "castrative" activity of LHRH-Lys-MDP and its chemical and antigenic structures. However, because LHRH antibody levels were not very high, mechanisms other than antibody response are discussed. Such totally synthesized molecules including a safe adjuvant could make a clinical use of LHRH immunization possible in endocrine-dependent cancers.

Acetylmuramyl-Alanyl-Isoglutamine↗

Sexual behavior in castrated male rats treated with monoamine synthesis inhibitors and testosterone.

Castrated male rats treated daily with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA, 20 mg/kg) started to display mounts, intromissions and ejaculations more rapidly in response to daily treatment with testosterone propionate (TP, 0.15 mg/kg) than NaCl-treated rats. Daily treatment with the catecholamine (CA) synthesis inhibitor alpha-methyl-p-tyrosine (alpha-MT, 20 mg/kg) had no effect on the behavioral response to subsequent TP treatment. The acceleration of TP-induced sexual behavior by PCPA pretreatment was inhibited by pretreatment with DL-5-HTP (20 mg/kg) but not with L-DOPA (12.5 mg/kg). Analyses of brain monoamines showed that the PCPA treatment reduced brain 5-HT levels and produced a marked inhibition of the 5-HT synthesis. The 5-HTP treatment restored brain 5-HT levels to normal. Daily treatment with PCPA also reduced brain CA levels and inhibited the CA synthesis but these biochemical effects were not related to the effects of PCPA on sexual behavior. Daily treatment with PCPA (40 mg/kg for 12 days) or treatment with 126 mg/kg PCPA for 3 days induced the complete pattern of sexual behavior in 5 of 9 and 19 of 30 castrated rats respectively without concurrent TP treatment. It is suggested that 5-HT exerts a modulating influence on sexual behavior in male rats.

Animals↗

Behavioral effects of long-term administration of an anabolic steroid in intact and castrated male Wistar rats.

Once a week, intact and castrated male Wistar rats were intramuscularly injected with a 0.2 ml suspension of either 0, 10, or 50 mg nandrolone decanoate in cottonseed oil, for 8 consecutive weeks. After the sixth injection, locomotor activity was measured in an open-field and the acquisition of lever press behavior was assessed in an autoshaping procedure. Subsequently, all subjects were exposed to four sessions of continuous reinforcement prior to one session in which the effects of steroid administration on extinction were assessed. Locomotor activity decreased for all groups of rats with continued exposure to the open-field, differences between groups were not observed. Rats treated with the highest dose of nandrolone decanoate spent more time in the margin of the open-field. There were no significant differences between groups on any of the learning measures. Long-term, high-dose steroid administration in conjunction with mild food deprivation inhibited growth in intact and castrated rats, while low dose administration affected body weight in intact rats only. Steroid administration resulted in heavier and enlarged kidneys and lighter testes as well. These results suggest that the administration of anabolic steroids not only produces observable physiological changes, but that it may also affect spontaneous behavior. The failure to find differences in learning indices may have been a function of the particular paradigms used in the present experiment.

Anabolic Agents↗

Influence of unilateral castration and increased plane of nutrition on sexual development of Holstein bulls. I. Growth and sperm production.

Sixty-five Holstein bull calves were used to study the effects of unilateral castration (UC) and increased plane of nutrition on the growth and development of the reproductive system. Bulls were slaughtered at 1 wk., 2, 4, 8 and 16 months. Half of each slaughter group above one week was unilaterally castrated at 7 days of age. Half of the bulls remaining at 6 months of age received 90% of their recommended daily TDN allowance while the remainder received 120%. Compensatory hypertrophy was evident as early as 2 months and the degree of compensation increased for the duration of the experiment (Age x UC, P<.01). By 16 months of age the remaining testis of UC animals was 73% heavier than the average testis weight of intact bulls. While epididymal weight was significantly increased by UC, seminal vesicle weight was not. UC bulls produced significantly more sperm per testis than intact bulls both from the onset of puberty to slaughter and for the 16 week period prior to slaughter. Testis sperm concentration was similar in UC and intact bulls. UC at one weel of age caused greater testis growth and greater sperm production per testis, but did not promote earlier puberty.

Journal Article↗

Testosterone, luteinizing hormone, follicle stimulating hormone, and prolactin response to unilateral castration in prepubertal Holstein bulls.

Hemicastration of Holstein bulls at 3 months of age resulted in increased (P<0.005) testicular weitht and testis sperm cell content at 330 days after treatment, but did not alter sperm cell concentration in the remaining hypertrophied testis. Radioimmuroassay of blood hormones at 1, 6, 12, and 24 weeks after treatment revealed that unilateral castration did not alter (P>0.1) basal levels or GnRH response profiles of either LH or testosterone compared to intact bulls. Hemicastration caused FSH to be elevated (P<0.01) compared to intact bulls at all sampling periods in both unstimulated and GnRH stimulated bulls. Prolactin varied with season and was greater (P<0.001) in hemicastrated bulls than in intact bulls at 1 and 6 weeks after treatment. Results indicate that unilateral castration at 3 months of age caused testicular hypertrophy of both steroidogenic and gametogenic function and this phenomena may be triggered by increased FSH or prolactin secretion, or both. Further, results indicate different testicular regulation mechanisms exist for pituitary LH and FSH release in bulls.

Journal Article↗

Serum follicle stimulating hormone, luteinizing hormone, and testosterone in sexually stimulated intact and unilaterally castrated rams.

Ten two-year-old intact (IN) and unilaterally castrated (UC) Targhee rams were exposed to an estrogenized ewe each week from June to October. Each week the rams were subjectively evaluated for libido (10 for high interest and 1 for no interest). Semen was collected from all cooperating rams and evaluated for volume, concentration, and motility. Every 2 wk, blood samples were obtained at -30 and 0 min before and 30 and 60 min after ewe access. Serum was harvested; follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were quantified by radioimmunoassay (RIA). Week 5 of ewe access was assigned as Week 1. Libido scores rose from a low on Week 1, with eight rams ejaculating, to a high on Week 12, with all rams ejaculating (Week 1, 5.0 +/- 1.0; Week 12, 10.0 +/- 0.0). The product of testis length and width was significantly greater in UC compared with IN rams (88.4 +/- 1.4 versus 73.2 +/- 1.0 cm(2), respectively). Serum FSH concentrations (ng/ml) were greater (P < 0.05) in UC than IN rams and dropped over the experimental period. Serum LH concentrations (ng/ml) were significantly greater in UC compared with IN rams. This difference was more pronounced in Weeks 1 and 3 compared with Weeks 11 and 13. Serum testosterone concentrations (ng/ml) were similar in UC and IN rams throughout the experiment. In conclusion, serum testosterone was not altered in UC rams; however, serum FSH and LH concentrations were increased in UC rams. Unilateral castration did not enhance the normal changes in semen quantity and quality in the rams from July to October.

Journal Article↗

Studies of pituitary-adrenal-testis interaction in sheep. III. The effects of repeated injections of adrenocorticotrophic hormone in recently castrated rams.

Twice daily for 5.5 d, 0.5 ug of long-acting adrenocorticotrophic hormone (ACTH, Synacthen-Depot) was administered to four rams castrated 17 d earlier. There was a progressive diminution in basal plasma follicle stimulating hormone (FSH) during and after treatment. ACTH also suppressed basal plasma luteinizing hormone (LH) concentrations and the maximum LH values reached and the quantity of LH released in response to the injection of 5 ug of gonadotrophin releasing hormone (GnRH). There was, however, evidence that the LH concentrations returned to pretreatment levels after ACTH treatment ceased. This experiment demonstrated that the effects of ACTH on LH are modulated by castration, but throughout this series of experiments ACTH always depressed LH activity. In contrast, FSH is affected by ACTH in different ways, depending on the season and the presence or absence of a testis.

Journal Article↗

Assessment of xylazine hydrochloride epidural analgesia for open castration of rams.

Epidural xylazine injected at the sacrococcygeal site 40 to 150 min prior to surgery (at a dose of 0.05 to 0.10 mg/kg) provided good analgesia during scrotal skin incision in all 20 experimental rams but in only 10 rams (50%) at incision and separation of tunica vaginalis, and 6 rams (30%) during ligation of the spermatic cord. There was a significant correlation between the decrease in heart rate and the dosage of epidural xylazine. Heart rate increased significantly during incision of the tunics and spermatic cord ligation but was not significantly correlated to the clinical assessment of analgesia. There was no significant correlation between the presence of surgical analgesia and the dosage of epidural xylazine: Pelvic limb ataxia was still evident in 12 rams (60%) at 8 h after epidural xylazine injection. Epidural xylazine provided good somatic analgesia during open castration of 20 rams but visceral analgesia was unpredictable. Factors in addition to the dosage of sacrococcygeal epidural xylazine affects the degree of surgical analgesia obtained for open castration of rams.

Journal Article↗

Studies of the slow releasing of testosterone from radiation-polymerized testicular prostheses implanted subcutaneously in the back of castrated rabbits.

A controlled release testicular prosthesis containing testosterone, which was previously dissolved in 2-hydroxyethyl methacrylate (HEMA) at a temperature of 80 degrees C, was prepared by radiation-induced polymerization in the supercooled state at a low temperature. The daily dose of testosterone released in vitro from the poly(HEMA) testicular prosthesis was kept constant at a rate of 5.5 +/- 1.5 mg/d throughout an experimental period of 900 d. In the in vivo experiments, the poly(HEMA) testicular prosthesis was implanted subcutaneously in the back of castrated rabbits over a maximum period of 11 mnth. The cumulative amounts of testosterone released in vitro and in vivo from the poly(HEMA) testicular prosthesis for a period of 11 mnth were found to be 2.1 g (30.0 wt% of initial drug) and 0.9 g (12.8 wt% of initial drug), respectively. The serum testosterone level in castrated rabbits with a poly(HEMA) testicular prosthesis rapidly decreased for periods up to 2 mnth (after increasing during the first 2 wk), then showed a moderate decrease for a few months, and finally held constant at a level of 10 ng/ml throughout the experimental period. It was concluded that a slight amount of testosterone is continuously released in vivo from the radiation-polymerized poly(HEMA) testicular prosthesis over a long period analogous with that in vitro.

Animals↗

Influence of castration and testosterone treatment on the vasoactive intestinal peptide receptor/effector system in rat prostatic epithelial cells.

The interaction of vasoactive intestinal peptide (VIP) with prostatic epithelial cells was studied after castration and testosterone replacement in pubertal and mature rats. The number of VIP receptors (but not the affinity) decreased 2 days after castration and returned to normal when subsequently treated with testosterone for 4 days. However, the stimulatory effect of VIP upon cyclic AMP accumulation was unaffected by the androgen withdrawal elicited by the surgical procedure. The results suggest the importance of androgens in the biosynthesis of VIP receptors and also in their coupling to adenylate cyclase by affecting the membrane fluidity.

Age Factors↗

Tyrosine hydroxylase and POMC mRNA in the arcuate region are increased by castration and hyperprolactinemia.

We have examined the changes which occur in neuronal expression of tyrosine hydroxylase (TH) and proopiomelanocortin (POMC) mRNA in response to castration and hyperprolactinemia (HP) in male rats. Steady-state mRNA levels were determined by quantitative in situ hybridization histochemistry (ISHH) using 35S-labeled synthetic 48-base oligodeoxynucleotide probes. Castration produced a 27% increase in TH mRNA in the periventricular and arcuate nuclei. PRL-exposed rats exhibited a further 27% increase in the level of TH mRNA and a striking 48% increase in POMC mRNA in periarcuate region cell bodies. These results indicate that gonadal steroids and PRL are involved, either directly or indirectly, in regulating the biosynthesis of TH and POMC in the hypothalamus.

Analysis of Variance↗

Daily changes in melatonin binding sites and the effect of castration.

The effect of castration and/or neonatal administration of testosterone propionate (TP) on 125I-melatonin binding and its daily changes was studied in rat anterior pituitary (AP) and in pars tuberalis/median eminence (PT/ME). In animals kept on a light/dark cycle of 12:12 h there was a marked increase in binding site density (Bmax) in the evening as compared to the morning, while there were no differences in the affinity (Kd). On a light/dark cycle of 8:16 h the daily rhythm in Bmax was abolished and the values were intermediate. Neonatal TP administration which increases the sensitivity of the reproductive axis to melatonin and photoperiodic regulations had no effect on the binding parameters in AP and in PT/ME. Castration, however, increased binding site density in AP by 85% while it had no effect on the affinity of the binding site (Kd).

Animals↗

Lack of tumorigenic response in the prostate gland of castrated F344 rats by 3,2'-dimethyl-4-aminobiphenyl given with methyltestosterone.

In an attempt to induce a high incidence of prostate carcinoma, 3,2'-dimethyl-4-aminobiphenyl (DMAB), a prostatic carcinogen, was given during the period of cell proliferation of the prostate gland induced by the administration of methyltestosterone (MT) to castrated F344 rats. Three weeks after the surgical castration, rats were given diet containing 300 ppm of MT for 2 weeks and basal for 2 weeks alternately 12 times. During each treatment with MT, one (group 1) or two (group 2) subcutaneous injections of 50 mg/kg body wt. of DMAB was given. After the last treatment of MT, a pellet of testosterone propionate (TP) was implanted in the subcutis of all animals until the end of the experiment (week 60). No carcinomas developed in the prostate gland of any of the rats. Atypical hyperplasia of the ventral lobe of prostate was found in 4 of 22 rats in group 1 and 2 of 20 rats in group 2. The incidences of atypical hyperplasia of the seminal vesicles in groups 1 and 2 were 64% and 75%, respectively. No pathological lesions in the prostate were observed in 32 rats given DMAB without MT treatment.

9,10-Dimethyl-1,2-benzanthracene↗

Growth hormone parameters at four ages in intact and castrated male and female cattle.

Plasma Growth hormone (GH) profiles, secretion rates (SR), metabolic clearance rates (MCR) of intravenously infused GH, and response to 0.0165, 0.067, and 0.267 microgram of growth hormone-releasing factor (GHRF)/kg body weight (bwt) were studied in intact and castrated male and female cattle (4 of each) at 5, 8, 12, and 15 mo of age. As cattle aged, overall GH levels in the plasma decreased (P less than .01), GH baseline concentrations declined (P less than .05), SR decreased (P less than .01), half-life of GH decreased (P less than .01), and the GH response to intravenous injections of GHRF declined (P less than .05). Bulls had elevated overall and baseline GH concentrations (P less than .05), greater amplitude and number of GH secretory periods (P less than .01), and greater SR (P less than .05) than steers, heifers, or ovariectomized heifers. Males had more frequent GH spikes and secretory periods of higher amplitudes, greater SR, and greater GH responses to 0.0165 microgram GHRF kg bwt (P less than .05) than females. Castration had no impact on the GH status of heifers. It is suggested that testosterone or its metabolites enhanced GH secretion in bulls.

Aging↗