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PubMed1982

Effects of cranial cervical ganglionectomy and castration of male lambs. III. Hormonal responses following administration to gonadotrophin releasing hormone (GnRH).

Entire and castrate male lambs, which were cranial cervical ganglionectomized (GX) or untreated, were utilized in a study of responses to intravenous GnRH; 24 animals were treated at both 101 and 277 days of age. GX caused a reduction in basal LH concentrations of both wethers and rams at the first sampling, but increased pre-injection levels of this hormone in 277 day old wethers. Basal LH levels of castrates were substantially higher than those of entires, but GX had no significant influence on pretreatment testosterone secretion in rams. GnRH treatment elevated plasma LH levels in all animals, while in entires increases in testosterone concentrations also occurred. Castration significantly increased peak LH levels together with total LH output. At neither age were the LH or testosterone reponses influenced significantly by GX, nor was the interaction of castration and GX significant for LH response data. The major effect of age at GnRH treatment was that markedly higher testosterone responses were recorded from the older rams.

Journal Article↗
PubMed1993

Estradiol modulation of PMA--and ionomycin-stimulated LH secretion from pituitaries of castrated rats.

Quartered pituitaries from castrated (72 h) +/- estradiol (E2)-treated (24 h) rats were used in a perifusion system to investigate estradiol modulation of ionomycin and ionomycin + PMA stimulated LH secretion. Estradiol enhanced the LH responses to GnRH (1 nM) and ionomycin (10 microM), and was necessary for the manifestation of PMA-stimulated (1 microM) LH secretion. Cycloheximide (5 microM) inhibited the E2-enhanced responses to GnRH, ionomycin and PMA. The protein synthesis inhibitor also partially suppressed the GnRH response from pituitaries of castrates, but was totally ineffective against the ionomycin-induced LH secretion. Protein synthesis-dependent, synergistic interactions between PMA and ionomycin were evident from pituitaries of castrates (even though PMA alone was an ineffective secretagogue). Synergistic interactions were not apparent from pituitaries of castrated + E2-treated rats. These results indicate that: (i) estradiol enhances the responsiveness of male gonadotropes to ionomycin and PMA by protein synthesis-dependent mechanisms which appear to mask their synergistic interactions; and (ii) increases in cytoplasmic Ca2+ might be a prerequisite for an expression of the involvement of PKC as a mediator of LH secretion in the absence of high concentrations of estradiol.

Animals↗
PubMed1991

Differential effects of neonatal castration on the development of sexually dimorphic brain areas in the gerbil.

We compared the effects of neonatal castration within 6 h of birth in the Mongolian gerbil on the development of the sexually dimorphic area pars compacta (SDApc) and supraschiasmatic nucleus (SCN). Development of these brain areas was also related to a masculine courtship ultrasonic vocalization, the frequency-modulated upsweep. Castration immediately after birth resulted in differential effects with complete or partial reduction of SCN and SDApc volumes, respectively, as compared to male values. The rates of ultrasonic calling of males castrated as neonates were also decreased to female levels. In sham-operated males, calling rates were positively correlated with the volume of the left SDApc, but not the right. Both the left and the right SDApc volumes were correlated with calling rates in males castrated as neonates. The asymmetric relationship between vocal behavior and area volume was specific to the SDApc. We suggest that in the neonate (a) the sensitivity of the SDApc to the differentiating effects of androgens differs from the SCN and (b) the asymmetric link between brain structure and vocal behavior depends on the effects of androgen within 6 h of birth.

Aging↗
PubMed1986

Effects of a long-acting LHRH agonist preparation on plasma gonadotropin and prolactin levels in castrated male rats and on the release of prolactin from ectopic pituitaries.

We have examined the effects of a single subcutaneous injection of an LHRH agonist, D-Trp-6-LHRH, in biodegradable microcapsules of poly(DL-lactide-co-glycolide) on plasma gonadotropin and prolactin (PRL) levels in castrated and in castrated-hypophysectomized-pituitary grafted (CAST-APX-GRAFT) male rats. The results were compared to the effects of daily injections of the same LHRH agonist dissolved in saline. In castrated rats, there were no significant alterations in plasma LH or PRL levels during the 10 days following the injection of LHRH agonist microcapsules, while FSH levels were generally reduced. In castrated males given daily injections of 6 micrograms of LHRH agonist in saline, plasma LH levels were significantly reduced while plasma PRL levels were not changed. In CAST-APX-GRAFT rats, both D-Trp-6-LHRH microcapsules and daily LHRH agonist injections appeared to increase plasma PRL levels. The pattern of changes in PRL release in both groups was similar, with levels on day 6 being significantly higher than those measured on days 1, 3 and 10 after onset of treatment. As expected, LH and FSH levels in these animals were extremely low. Immunoreactive D-Trp-6-LHRH was consistently detectable in the plasma of CAST-APX-GRAFT animals after microcapsule administration, whereas in animals given daily injections of this agonist in saline, its plasma concentrations were often below the detectability limit of the employed assay. These findings suggest that the LHRH agonist, D-Trp-6-LHRH, is capable of causing a short term stimulation of PRL release from ectopic pituitaries. Elevation of plasma LH levels is apparently not required for this effect.

Animals↗
PubMed1991

Diabetes-related renal growth and IGF-I accumulation in castrated rats.

The effects of castration on diabetes-related renal growth and IGF-I regulation were studied. In the rat, prepubertal castration is associated with a normal or increased surge in plasma insulin-like growth factor I (IGF-I) at the time of 'puberty'. In order to determine the role of sex steroids in the development of diabetes-related kidney growth and IGF-I regulation, Sprague-Dawley rats were castrated at the age of 4 weeks and streptozotocin diabetes was induced at the age of 13 weeks. The development of renal enlargement and kidney IGF-I levels was studied over the following 7 days. Kidney weight in diabetic animals was significantly greater than in controls, and by day 7, had increased by 27% (1.20 +/- 0.03 vs 0.94 +/- 0.03 g, P less than 0.001). Kidney IGF-I content was significantly elevated in diabetic rats, peaking on day 1 (diabetic, 1159 +/- 302 ng/g vs control, 237 +/- 53 ng/g, P less than 0.001) and remaining higher than control levels throughout the 7 days of the experiment. The pattern of diabetes-related kidney growth and IGF-I regulation in castrated rats resembles that of age matched intact postpubertal controls, suggesting that sex steroids do not have a direct role in these phenomena.

Aging↗
PubMedDate not supplied

Selective effect of castration on the anterior pituitary VIP receptor of male rats.

We investigated the effect of surgical castration of male rats on the binding of [Tyr(125I)10]VIP to receptors on the anterior pituitary gland, superior mesenteric artery, brain, liver, and prostate gland. In anterior pituitary membranes the maximum number of VIP binding sites was increased whereas binding affinity was decreased 24 hours following castration. In particular, the high affinity equilibrium dissociation constant (KD) increased from 0.13 +/- 0.02 nM (mean +/- SEM) to 0.67 +/- 0.07 nM and the maximum number of high affinity binding sites (Bmax) increased from 71 +/- 9 to 470 +/- 112 fmol/mg protein. No significant change was observed in the other tissues. Anesthesia or sham operation did not alter the anterior pituitary VIP receptor binding parameters. The changes in the VIP receptor 24 hours after castration were prevented by prior injection of testosterone. These findings demonstrate tissue-selective alterations to the anterior pituitary VIP receptor by castration that are likely mediated by withdrawal of testosterone.

Animals↗
PubMed1989

Greater inhibitory effects for testosterone than castration in rat thyroid tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine.

The effects of testosterone and castration on thyroid tumorigenesis subsequent to initiation by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were investigated in male Wistar rats. Following 2 weekly i.p. injections of DHPN at the dose of 210 mg/100 g body weight, testosterone was administered in the diet at concentrations of 0.15% or 0.03% for 28 weeks. Castration was performed on a separate group of animals 1 week after the final injection of DHPN. The incidence of thyroid adenomas and carcinomas were 69% (9/13) and 15% (2/13), respectively, in rats treated with DHPN alone, 0% (0/15) and 6% (1/15) in rats treated with DHPN and 0.15% testosterone, 13% (2/15) and 13% (2/15) in rats treated with DHPN and 0.03% testosterone and 33% (5/15) and 33% (5/15) in the castrated animals initiated by DHPN. The reduction in adenoma development associated with testosterone treatment was significant at both concentrations. In contrast, only a tendency for decrease of thyroid tumor incidence was observed in rats castrated.

Animals↗
PubMed1995

Efficacy of injectable doramectin in the protection of castrated cattle against field infestations of Cochliomyia hominivorax.

Three studies were conducted in Latin America--one in Venezuela, one in Argentina and one in Brazil--using a common protocol to investigate the efficacy of a single subcutaneous injection of doramectin in the prevention and control of Cochliomyia hominivorax infestations in castrated cattle. In each study, two groups of 20-28 animals each were allocated to a treated (T1) or to a control (T2) group on the basis of body weights. Animals of T1 received doramectin at 200 micrograms kg-1 (1 ml per 50 kg) and animals of T2 received saline solution at 1 ml per 50 kg of live weight. After treatment all cattle were castrated surgically. Animals were examined on treatment day and at 2, 4, 6 and 12 days post-treatment. At each observation day, the presence of C. hominivorax infestations was recorded. Doramectin was 100% effective in the prevention and control of screwworm strikes in castrated cattle exposed to continuous field infestations of C. hominivorax in tropical and subtropical areas of Latin America. Over the 12 day duration of the studies, 85%, 60% and 65% of animals in the control groups had infested wounds in Venezuela, Argentina and Brazil, respectively. Affected animals required repeated therapeutic treatment, whereas none of the doramectin-treated cattle were infested (P < 0.0001). A high proportion of the castration wounds in doramectin-treated cattle had the presence of characteristic C. hominivorax eggs but none developed into larvae. There were no clinical signs of adverse reactions to treatment in any of the three studies.

Animals↗
PubMed1990

The effects of testosterone or insulin treatment on contractile responses of the rat vas deferens following castration or streptozotocin-induced diabetes mellitus.

1. Castration and streptozotocin-induced diabetes produce significant decreases in serum testosterone levels accompanied by decreased vas deferens weights, a decreased responsiveness to nerve stimulation, and altered contractile responses to carbachol and phenylephrine. 2. Treatment of castrated rats with testosterone for 8 weeks prevented the decreased vas deferens weights and contractile changes associated with castration. 3. Treatment of diabetic rats with testosterone for 8 weeks prevented the decreased vas deferens weights and the supersensitivity to contractile agonists associated with diabetes. Testosterone treatment only partially prevented the decreased response to nerve stimulation. 4. Treatment of diabetic rats with testosterone plus insulin for 8 weeks prevented the decreased vas deferens weights and decreased the sensitivity to carbachol and phenylephrine compared to controls. Testosterone plus insulin treatment prevented the decreased response to nerve stimulation. 5. There were no differences in the IC50 values for nitrendipine among any of the groups studied, suggesting that the contractile changes observed in vasa deferentia following castration or diabetes are not the result of changes in calcium movements. 6. The results suggest that decreased testosterone levels are at least partially responsible for the changes in contractility of the vas deferens of streptozotocin-diabetic rats.

Animals↗
PubMed1987

The effects of castration, testosterone replacement and photoperiod upon hypothalamic beta-endorphin levels in the male Syrian hamster.

Syrian hamsters kept in long day-lengths have active gonads and high circulating levels of gonadal steroids. Under the influence of the pineal gland, animals exposed to short photoperiods undergo testicular regression, have low circulating levels of testosterone and gonadotrophins and elevated levels of beta-endorphin within the hypothalamus. This paper describes the interaction between testosterone and photoperiod in the regulation of beta-endorphin levels in three regions of the hypothalamus. Hypothalamic beta-endorphin levels were measured by a combination of high-performance liquid chromatography and radioimmunoassay techniques that allows separation of the beta-endorphin (1-31) peptide from its metabolites and precursors. All of the beta-endorphin-like immunoreactivity in the hypothalamus of the male hamster, in both photoinhibited and photostimulated conditions, was found to represent the 31-amino-acid peptide. In photostimulated hamsters, chronic castration was associated with a significant increase of beta-endorphin levels in the anterior hypothalamus and mediobasal hypothalamus, which was reversed by treatment with exogenous testosterone. Castration prevented the ability of naloxone, an opiate receptor antagonist, to release luteinizing hormone, and this effect was also reversed by exogenous steroid. In photoinhibited hamsters, however, castration had no effect upon beta-endorphin levels in the preoptic area or mediobasal hypothalamus, and there was only a small increment in the anterior hypothalamus. Significantly, beta-endorphin levels in all areas of the hypothalamus of photoinhibited castrates were not decreased by testosterone treatment. In addition, administration of exogenous testosterone did not restore sensitivity to naloxone in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Dissociation of the effects of castration and testosterone replacement on sexual behavior and neural metabolism of dopamine in the male rat.

Sexually experienced, adult male rats were either castrated, castrated and implanted SC with a Silastic capsule containing testosterone (T), or sham operated. Coital performance of castrates gradually declined such that 4 weeks after surgery no males in this group ejaculated whereas 89% and 100%, respectively, of the rats in the castrated, T-treated and the sham-operated groups displayed ejaculation. Males in all three groups were decapitated 33-34 days post-operatively after 10 min exposure either to the behavioral test chamber, with an estrous female restrained in one corner behind a wire mesh screen, or to a home cage. Brains were quickly removed and the caudate-putamen, nucleus accumbens, septum, and preoptic area/anterior hypothalamus were frozen and saved for later estimation of dopamine (DA) and two neural metabolites of DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The concentrations of DA, DOPAC, and HVA, as well as the ratio of DOPAC/DA, did not differ significantly in any of the 4 brain regions assayed among males in the three endocrine groups, regardless of whether they were killed after exposure to an estrous female or a home cage. The results fail to support the hypothesis that T-induced alterations in neurotransmission in nigro-striatal, mesolimbic, or incertohypothalamic DA pathways mediate the activational effect of this steroid on masculine sexual behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Neurokinin A levels in the hypothalamus of rats and mice: effects of castration, gonadal steroids and expression of heterologous growth hormone genes.

Neurokinin A is a decapeptide with pharmacological activities and localizations similar to those of substance P. In this report we describe the effects of castration and administration of testosterone, dihydrotestosterone and estradiol, on neurokinin A levels in the hypothalamus of male rats. The effects of estradiol and testosterone on hypothalamic neurokinin A were also examined in normal mice and in transgenic mice carrying the genes for human or bovine growth hormone (hGH, bGH, respectively). Either acute or prolonged castration was followed by a decrease of neurokinin A concentrations in the hypothalamus of male rats. The substitutive administration of testosterone propionate or estradiol benzoate for 14 days resulted in an increase of hypothalamic neurokinin A levels above the values found in intact animals. A lower dose of testosterone propionate or dihydrotestosterone also increased hypothalamic neurokinin A levels in the hypothalamus of castrated rats. In normal intact male mice a single injection of estradiol benzoate significantly increased hypothalamic neurokinin A levels. A similar effect was observed in transgenic mice carrying the bGH gene with phosphoenolpyruvate carboxykinase (PEPCK) promoter, while mice carrying the hGH gene failed to show any response to estradiol. In castrated male mice, either normal or transgenic, carrying the bGH gene with metallothionein promoter, a single injection of testosterone propionate significantly increased neurokinin A levels in the hypothalamus. It is concluded that sex steroids may regulate the levels of neurokinin A in the hypothalamus of rats and mice.

Animals↗
PubMed2005

Failure to achieve castration levels in patients using leuprolide acetate in locally advanced prostate cancer.

OBJECTIVE: In a cross-sectional, retrospective, non-randomised study to investigate the possibility that some patients treated with luteinizing hormone releasing hormone analogues (LHRH analogues) fail to reach castration levels of serum testosterone. METHODS: 40 patients treated with a 3-monthly formulation of leuprolide acetate and continuous use of an oral antiandrogen ("Leu group") and 25 patients treated with a 3-monthly formulation of goserelin acetate and an oral antiandrogen for one month ("Gos group") were identified from our hospital's registry. Serum testosterone was measured during treatment with the respective LHRH-analogue and compared between the two groups. In the Leu group, serum testosterone was measured during week 11 or 12 of treatment. In the Gos group, serum testosterone was assessed during week 23 or 24. RESULTS: Four patients (10%) treated with leuprolide acetate failed to reach the castration level of serum testosterone after treatment with one injection of a three-monthly formulation of leuprolide acetate. All patients treated with goserelin acetate achieved the castration level. CONCLUSION: Although the overwhelming majority of prostate cancer patients during treatment of LHRH analogue achieve serum testosterone values within the castration range, individual patients may fail to reach this therapeutic goal, probably more often during treatment with leuprolide acetate than with goserelin acetate.

Aged↗
PubMed2005

The magnitude of early castration-induced primary tumour regression in prostate cancer does not predict clinical outcome.

INTRODUCTION: This study was designed to test whether early castration-induced short-term cellular changes in primary prostate tumours could predict clinical outcome in advanced disease. PATIENTS AND METHODS: Biopsies from 83 patients obtained before and within two weeks after surgical castration were investigated. Tumour epithelial cell apoptosis, proliferation, and prostate specific antigen (PSA) levels were quantified using immunohistochemistry, laser capture micro-dissection, and real time RT-PCR. Cellular effects were related to changes in serum PSA levels and clinical outcome. RESULTS: Decreased proliferation and PSA mRNA levels, and increased apoptosis were observed in most tumours. These early cellular responses were not correlated to each other and did not predict serum PSA response or cancer-specific survival. A nadir PSA level below 1 ng/ml predicted a longer cancer-specific survival after castration therapy. CONCLUSION: Castration therapy causes primary tumour regression in most patients with advanced prostate cancer, but these primary tumour effects are not predictive for systemic disease control. Studies of early changes in metastases during hormonal therapy will probably give more predictive information for clinical outcome than further studies in primary tumours.

Aged↗
PubMed2007

The impact of prior radical prostatectomy in men with metastatic castration recurrent prostate cancer: a pooled analysis of 9 Cancer and Leukemia Group B Trials.

PURPOSE: A prior report suggested that radical prostatectomy may confer a survival advantage to patients with metastatic castration recurrent prostate cancer. Therefore, a pooled analysis of 9 trials performed by Cancer and Leukemia Group B was done to determine if men with metastatic castration recurrent prostate cancer who underwent prior prostatectomy had improved clinical outcomes, such as overall, prostate specific, progression-free and PSA progression-free survival, than men who did not undergo prior prostatectomy. MATERIALS AND METHODS: Data from 9 multi-institutional trials performed by Cancer and Leukemia Group B were combined. Eligible patients had progressive prostate cancer during androgen deprivation therapy, Eastern Cooperative Oncology Group performance status 0-2, and adequate hematological, renal and hepatic functions. The proportional hazards model was used to assess the prognostic importance of radical prostatectomy for predicting clinical outcomes. RESULTS: Of 1,238 men 310 (25%) underwent prostatectomy. Median survival was 14.7 (95% CI 12.9-16.7) and 14.5 months (95% CI 13.5-15.7) in men who did and did not undergo prostatectomy, respectively. The HR for death was 1.03 (95% CI 0.90-1.19, p = 0.65) in men with vs without prostatectomy. CONCLUSIONS: Prior prostatectomy in men with metastatic castration recurrent prostate cancer who were subsequently enrolled on clinical trials for cancer treatment had similar survival compared to men who did not undergo prior prostatectomy. These data do not support another report suggesting that prior prostatectomy confers a subsequent survival advantage in men with castration recurrent prostate cancer.

Aged↗
PubMed2004

One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men.

The results of several recent studies suggest that estrogen and testosterone play an important role in the modulation of mood and cognitive function in women, and preliminary evidence indicates that these hormones may also modulate the levels of beta-amyloid (Abeta), a 4 Kilo Dalton peptide that is likely to be involved in the pathogenesis of Alzheimer's disease. However, the physiological and clinical effects of reversible castration remain unclear and no systematic data is currently available for men. We designed the present study to investigate the effects of reversible chemical castration on the mood and cognitive performance of men treated for prostate cancer, as well as its impact on the levels of plasma Abeta. Forty men with prostate cancer were clinically treated with androgen blockade therapy (flutamide and leuprolide) for 36 weeks and subsequently followed up for another 18 weeks after treatment was discontinued. All subjects received a comprehensive clinical, neuropsychological and biochemical evaluation that included the use of the Beck Depression (BDI) and Anxiety Inventories (BAI), several subtests of the Wechsler Memory and Intelligence Scales (Word Lists-WL, Verbal Paired Associates-VPA, Visual Reproduction-VR and Block Design-BD), and biochemical monitoring of changes in estrogen, testosterone and Abeta levels. Chemical castration was associated with a rapid and marked decline in the levels of testosterone and estradiol, and significant increase in plasma Abeta levels. Treatment was associated with increased BDI (p = 0.004) and BAI scores (p < 0.001), although such changes were of questionable clinical significance (i.e., few subjects had scores > or = 13). CAMCOG (p = 0.046) and WL recall total scores (p < 0.001) improved significantly after androgen blockade treatment was discontinued, but visuospatial abilities, as assessed by BD, was not influenced by the introduction or discontinuation of treatment. There was a significant negative correlation between changes in Abeta levels and subjects' WL total score change between weeks 36 and 54 (r = -0.452, p = 0.012). The results of this naturalistic study indicate that chemical castration is associated with a significant rise in the plasma levels of Abeta and, clinically, with increased depression and anxiety scores. The discontinuation of treatment is associated with better cognitive performance, most noticeably of verbal memory. The performance of subjects on the WL test was negatively correlated with plasma levels of Abeta, but the clinical significance of this finding remains to be determined.

Adult↗
PubMed2005

Current practice relating to equine castration in the UK.

This study aimed to characterise current practice relating to equine castration in the UK. A questionnaire was posted to all 655 veterinary practices specified to provide veterinary care for horses, or classified as specialist equine practices. Respondents were asked to cite the number of equine castrations performed annually by the practice, describe techniques used for castration, outline anaesthetic/sedative/analgesic drug protocols used and provide details of post-operative medication. There was a 43% response rate to the questionnaire. Considerable variation in techniques and analgesia provision was identified, with the majority of respondents using a number of sedation/anaesthetic protocols rather than a single technique. This characterisation of current practice provides a useful platform from which subsequent investigations into welfare implications of current equine castration techniques can be directed.

Analgesics↗
PubMed2005

Effect of local anaesthesia on short- and long-term pain induced by two bloodless castration methods in calves.

Behavioural and cortisol responses of calves were used as indicators of pain to assess short- and long-term effects of bloodless castration methods with and without local anaesthesia. Seventy calves, aged 21-28 days, were control handled (20) or castrated using the Burdizzo (25) or rubber ring technique (25). Either 10 mL lidocaine or NaCl were distributed in both spermatic cords and the scrotal neck. The plasma cortisol response was recorded for 72 h, and behavioural and clinical traits monitored over a three month period. Local anaesthesia reduced the level of indicators of acute pain after both the Burdizzo and rubber ring techniques. It did not, however, result in a totally painless castration. As there was evidence of chronic pain lasting for several weeks after rubber ring castration, the Burdizzo method is judged to be preferable to the rubber ring technique.

Anesthesia, Local↗