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PubMed1999

Castration does not inhibit aggressive behavior in adult male prairie voles (Microtus ochrogaster).

The relationship between castration and reduced male aggression is well established. However, anecdotal observations of male prairie voles (Microtus ochrogaster) suggest that castration does not reduce aggressive behavior. To investigate the role of testicular androgens on aggressive behavior, castrated or gonadally intact male prairie voles were paired in a neutral arena with a gonadally intact vole. Castration did not reduce the frequency of intermale aggression. In Experiment 2, aggressive behavior was examined further using resident-intruder, grouped aggression, and aggression against a lactating female models. Again, castration did not affect the frequency of aggression in male prairie voles. Taken together, the results of this study suggest that aggressive behavior may be independent of gonadal steroid hormones in adult male prairie voles.

Aggression↗

PubMed1996

Protein-bound and unbound forms of plasma cortisol in piglets after castration at seven or 14 days of age.

Male piglets from seven litters were used to evaluate the long-term effects of castration and age at castration on the concentrations of cortisol and its distribution in peripheral plasma. The piglets were allotted to one of three groups of 12 animals according to whether they had been castrated at seven or 14 days old or left intact. The animals were weighed and blood samples were collected from the anterior vena cava at three, seven, 10, 14, 17, 21, 28, 35 and 42 days of age. The plasma concentrations of albumin, total protein, cortisol, and the percentage distribution of cortisol among corticosteroid binding globulin-bound (CBG-bound), albumin-bound and unbound forms, were determined. Castration at seven or 14 days of age had no effect on any of the parameters measured. In all the piglets, the percentage of unbound cortisol decreased (P < 0.001) from 24.5 to 11.6 per cent over the period of sampling. The percentage of CBG-bound cortisol increased (P < 0.001) from 19 per cent on day 17 to 47 per cent on day 21, and albumin-bound cortisol declined from 61 to 37 per cent over the same period. These results agree with previous findings of age-related changes in the percentage distribution of cortisol in the piglet and demonstrate that these patterns are unaffected by castration.

Age Factors↗

PubMedDate not supplied

Influence of age, castration, and testosterone on T cell subsets in healthy and leukemia grafted mice.

The distribution of T cell subsets in pubertal (2 months) and post-pubertal (10 months) mice showed a significant decrease in the percentage of CD4+ splenocytes and peripheral blood lymphocytes (PBL) with age, unlike the percentage of CD8+ cells in PBL, which remained unchanged. The change in the distribution of T cell subsets in the spleen and blood occurred in 2 months old castrated mice, as in 10 months old animals. P388 tumor grew better in post-pubertal and in castrated mice than in young mice. The intact mice survived longer than the castrated ones. The relative number of CD4+, CD8+ and CD2+ splenocytes was lower in transplanted intact mice than that in controls. The CD8+ and CD2+ subsets in the blood of 2 months transplanted mice were higher than those in controls, whereas in PBL, in 10 months old and castrated mice, the T lymphocyte subsets remain unchanged. Depo-testosterone (DT) injection strongly reduced weight and tumor growth in all the intact and castrated animals. A significant correlation is observed between the tumor weight and testosterone level in the plasma of the 2 months old DT treated mice. Moreover, DT injection induced a significant increase in the percentage of blood CD8+ cells in all the batches. These data indicate that physiologically, androgens affect the age-related distribution of lymphocyte T subsets and suggest that they slow down tumor growth, besides causing a direct effect, through an immunological process.

Age Factors↗

PubMed2002

Canine prostate carcinoma: epidemiological evidence of an increased risk in castrated dogs.

The present retrospective study investigated the frequency of prostate carcinoma (PCA) among prostate abnormalities in dogs and determined whether castration influences the incidence of PCA in dogs. During the years 1993-1998, 15,363 male dogs were admitted to the Utrecht University Clinic of Companion Animals, and of these dogs 225 were diagnosed with prostatic disease. In addition, another 206 male dogs were diagnosed as having prostatic disease based on cytologic examination of aspiration biopsies submitted by referring veterinarians. Benign prostatic hyperplasia was diagnosed in 246 dogs (57.1%), prostatitis in 83 dogs (19.3%), and PCA in 56 dogs (13%). Dogs with PCA were significantly older (mean age=9.9 years) than dogs with other prostatic diseases (mean age=8.4 years). The Bouvier des Flandres breed had an increased risk (odds ratio (OR)=8.44; 95% CI 4.38-16.1) of having PCA. Castration (26/56) increased the risk (OR=4.34; 95% CI 2.48-7.62) of PCA. The mean age at diagnosis of PCA in castrated dogs and in intact male dogs was not significantly different. The interval between castration and onset of prostatic problems was highly variable, suggesting that castration does not initiate the development of PCA in the dog, but it does favour tumor progression.

Age Factors↗

PubMed1998

Comparison of methods for the reduction of acute pain produced by rubber ring castration or tail docking of week-old lambs.

Behavioural and plasma cortisol changes were recorded for groups of eight Suffolk x Greyface lambs subjected to castration or tail docking using rubber rings with and without local anaesthetic treatment. Immediately after application of the rubber ring, local anaesthetic (2 x 0.2 ml 2% lignocaine) was administered either by needle and syringe or by high-pressure needleless injection into each side of the neck of the scrotum or tail at the site of the ring, or by high pressure needleless injection into the testes before ring application. In other groups, the innervation to the scrotum or tail was disabled by crushing with a powered bloodless castrator just proximal to the ring. Measurements were recorded in groups of control (handled) lambs, with and without local anaesthetic treatment. Application of local anaesthetic by high pressure needleless injection had little effect on either plasma cortisol values or behaviour of control lambs. For castration, application of the bloodless castrator and/or local anaesthetic at the ring site reduced the peak plasma cortisol concentration by 50% (P < or = 0.01), the incidence of active behavioural responses by 80 and 64% (P < or = 0.01) respectively, and the time spent in abnormal postures by 68 and 59% (P < or = 0.01) respectively. Both methods were effective in reducing pain for tail docking [active behavioural responses reduced by more than 80% (P < or = 0.01) and abnormal postures by 56% (P < or = 0.01)], although local anaesthetic was more effective, reducing the peak cortisol by 60% (P < or = 0.01) [crushing by 44% (P > 0.05)]. Injection of local anaesthetic into the testes was less effective than injection into the neck of the scrotum at the site of the ring [reduction in abnormal lying postures (P < or = 0.05), 45 vs 71%, respectively]. The rapid action, effectiveness, and ease of application of these experimental methods may provide the basis for commercially viable methods for reducing the acute pain produced by rubber ring castration and tail docking of lambs.

Anesthetics, Local↗

PubMed2003

[Delegation of castration of calves and lambs to the livestock owner: internet survey of members of the Swiss Association for Ruminant Medicine].

According to the Swiss Federal law on animal protection and welfare, painful manipulations in animals have to be performed by a veterinarian under local or general anaesthesia, except for some specifically listed surgical interventions (article 65 of the by-law on animal protection). On September 1, 2001, castration of calves and lambs has been deleted from this list of exceptions. Since then, several pressure groups have requested these interventions to be delegated to the producers for economical reasons. The current article describes the results of a web-based survey on this subject, conducted among the members of the Swiss Association of ruminant practitioners (SARP). Two separate questionnaires--one focused on calves and one on lambs--were made available to the members of the SARP for a duration of 3 months as pdf-files on the homepage of the SARP (www.svwasmr.ch). On December 31, 2002, the deadline for submission of the completed questionnaires, the membership of the SARP was constituted of 360 practicing veterinarians. The response rate was 25%. Close to a hundred percents of the responding veterinarians expressed the expectation that the SARP publish guidelines on the castration of calves and lambs. An overwhelming majority refused the delegation of castrations to the producers, and further stated that they were not ready to accept any responsibility for interventions performed by the producers. However, a third of the responding veterinarians judged the expected workload for the castration of lambs to presumably exceed their current capacity. It is concluded from the results of this survey that the board of the SARP should urgently elaborate, discuss, and propose novel and innovative concepts to solve the issue of castration of calves and lambs.

Animal Welfare↗

PubMed1998

Short-term cellular effects induced by castration therapy in relation to clinical outcome in prostate cancer.

To explore the relationship between short-term effects of castration therapy and clinical response, biopsies obtained before and a week after castration therapy from 15 responding and 13 non-responding patients with prostate cancer were investigated. The biopsies were assessed for regressive morphology, apoptotic index by morphological criteria, nuclear area, and immunoreactivity (IR) for Ki-67, p53, bcl-2, bax and Fas. The index was defined as the percentage of immunoreactive cells in a tumour. Regressive morphology was observed in 14 out of 15 responding tumours after therapy, compared with 4 out of 13 non-responders (P < 0.001). Median tumour epithelial cell nuclear area and Ki-67 index decreased equally in both groups. The median apoptotic index increased from 2.6 to 3.5 after castration among responders (P < 0.05), whereas it remained at 2.8 among non-responders. p53 IR was present in three tumours before castration; after therapy p53 reactivity was seen in three additional tumours belonging to the responding group. Median bcl-2 index increased in responders from 1.5 to 10.0 (P < 0.05), and in non-responders from 0.08 to 2.7 (P < 0.05). Bax IR and Fas IR were present in all tumours before therapy and unchanged after therapy. Thus, regressive morphology and an increase in apoptotic index were related to a favourable clinical response. These data suggest that it might be possible to predict the effect of castration therapy by examining tumour biopsies shortly after treatment.

Aged↗

PubMed2002

Effect of castration on endothelin receptors.

Endothelin (ET) plays a pivotal role in the pathogenesis of cell growth disorders such as cancer. Atrasentan (ABT-627), a selective antagonist for the ET receptor A (ET(A)), has shown benefit in controlling disease progression in men with hormone refractory prostate cancer who have undergone aggressive hormone ablation therapy. It is not known how hormone ablation affects ET-binding sites, although ET-1 and ET(A) expression are found to be elevated in prostate cancer patients. In this study, we examined the effect of castration on ET receptor binding in male beagle dogs. Three dogs were surgically castrated and another three sham-operated. The animals were sacrificed 1 week after operation and membranes were prepared from the prostate, heart, brain, kidney, liver and lung for ET-1, ET-3 and angiotensin II (A-II, as a control) binding studies. No significant difference in A-II binding was observed between castrated and sham-operated animals. However, ET-1 and ET-3 binding to prostate and brain membranes were altered significantly. From saturation binding studies using ET-1 in the prostate, the K(d) and B(max) values increased from 0.043 nM and 0.094 pmol/mg respectively in sham-operated dogs to 0.104 nM and 0.311 pmol/mg respectively in castrated animals. These results indicate that surgical castration in dogs produces a change in the ET receptor density in the prostate and brain, and may have implications for the effect of hormone ablation therapy on ET receptor expression in prostate cancer patients.

Angiotensin II↗

PubMed2003

Changes in the EEG during castration in horses and ponies anaesthetized with halothane.

OBJECTIVE: To identify changes in the amplitude spectrum of the electroencephalogram (EEG) during a standardized surgical model of nociception in horses. ANIMALS: Thirteen entire male horses and ponies referred to Division of Clinical Veterinary Science, Bristol (n = 9) and Department of Clinical Veterinary Medicine (n = 4) for castration. MATERIALS AND METHODS: Following pre-anaesthetic medication with acepromazine, anaesthesia was induced with guaiphenesin and thiopental and maintained with halothane in oxygen. The EEG was recorded continuously using subcutaneous needle electrodes. Additional monitoring comprised ECG, arterial blood pressure, blood gas analysis, airway gases, and body temperature. All animals were castrated using a closed technique. The raw EEG was analysed after completion of each investigation and the EEG variables median frequency (F50), spectral edge frequency (SEF) 95% and total amplitude were derived from the spectra using standard techniques. The mean values of EEG variables recorded during a baseline time period (recorded before the start of surgery) and castration of each testicle were compared using analysis of variance for repeated measures. RESULTS: Total amplitude (Atot) decreased and F50 increased during castration of each testicle compared to the baseline time period [(89.0 +/- 7.8% testicle 1, 87.0 +/- 7.8% testicle 2) and (110.0 +/- 15.0% testicle 1, 109.0 +/- 15.0% testicle 2), respectively]. Changes in SEF 95% were not significant. CONCLUSIONS: De-synchronization was identified in the EEG during the nociceptive stimulus of castration. The results suggest that an increase in F50 may be a specific marker for nociception in the horse. CLINICAL RELEVANCE: Studies investigating the efficacy of analgesic agents in horses are limited by difficulties in peri-operative pain assessment. This model, using EEG changes associated with nociceptive stimulation, can be used to investigate the anti-nociceptive efficacy of different anaesthetic agents in the horse.

Anesthetics, Inhalation↗

PubMed2001

Novel male mice show gradual decline in the capacity to disrupt early pregnancy and in urinary excretion of testosterone and 17 beta-estradiol during the weeks immediately following castration.

Novel male mice can disrupt intrauterine implantation of fertilized ova in inseminated females. Evidence indicates mediation by androgen-dependent excretions. This study was designed to examine the time course of males' ability to disrupt pregnancy following castration and relate this to their urinary excretion of testosterone and 17 beta-estradiol. During days 1-5 of pregnancy, previously inseminated females were housed underneath castrated novel males at various intervals after the surgery. Castrated males generally continued to disrupt pregnancy during the initial weeks after surgery. Progressively, the probability of retention of pregnancy increased as a linear function of time since castration. There was an apparent asymptote, where the majority of females remained pregnant, beginning at about 6 weeks following surgery. Males' excretion of testosterone and 17 beta-estradiol in urine, measured via ELISA procedures, diminished gradually during the weeks after castration.

Animals↗

PubMed2007

The effect of chronic nicotine administration on bone mineral content and bone strength in normal and castrated male rats.

Tobacco, containing nicotine as the principal pharmacologically active chemical, has been identified as being a risk factor for the development of osteoporosis. Thirty-two male Wistar rats of two months of age were castrated or sham operated to evaluate the effects of long-term administration (four months) of nicotine in drinking water (9.0 mg/kg/day). The presence of cotinine in urine confirmed successful delivery of nicotine. The bones were tested mechanically by a three point bending test in a Mini Bionix (MTA) testing system. The bones from castrated rats were characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone (9%) and femoral cortical thickness. When intact rats were treated with a high dose of nicotine, nicotine had negative effect on tibial bone density as well as ash, calcium, phosphate content and significantly altered the mechanical properties of bone (12%) and femoral cortical thickness compared to intact animals. Nicotine itself does not exert any anti-androgenic effect and does not produce changes in the weight of seminal vesicles. Nicotine-induced bone loss is associated with high bone turnover in the male rats as expressed by increased TrACP and B-ALP. When castrated rats were treated with the high dose of nicotine the changes in bone density resulting from castration were not further potentiated. These results document the efficacy of nicotine at high doses to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of nicotine as a risk factor for osteoporosis.

Alkaline Phosphatase↗

PubMed1986

Response of pre-pubertally castrated rams and ewes to artificial photoperiod--changes in plasma LH and prolactin.

Castrate rams and ovariectomized ewes were maintained in the presence of entire rams and ewes and subjected to successive periods of alternating 6 h light:18 h darkness ('short' days) and 18 h light:6 h darkness ('long' days) preceded by a period of 12 h light:12 h darkness ('constant' light days). Plasma concentrations of LH and prolactin were measured in the castrate animals in order to determine how LH and prolactin secretion responded to the artificial light regime and corresponding periods of elevated or depressed testicular and ovarian activity in the entire rams and ewes. There was no variation in mean plasma LH concentrations or LH pulse frequency with either the changes in photoperiod or the phases of gonadal activity in the entire animals. However, there was a highly significant (P less than 0.001) relationship between prolactin secretion and the artificial photoperiod in both castrate groups with high and low levels coinciding with long and short days respectively. In addition, there was a marginally significant (P less than 0.1) relationship between prolactin secretion in the castrate ram and the stage of testicular activity in the entire rams with elevated levels associated with regressed activity. Prolactin secretion in the ovariectomized ewes was significantly (P less than 0.05) related to the phase of ovarian development with high levels associated with acyclic activity. It is concluded that LH secretion and pituitary responsiveness to exogenous GnRH were not modified by the artificial light regime. However, the changing light pattern was physiologically 'perceived' by the castrate animals as indicted by a concomitant variation in plasma prolactin concentrations.

Animals↗

PubMed1996

Behavioural and cortisol responses of lambs to castration and tailing using different methods.

Lambs at 4-5 weeks of age were studied during the first 4 hours after castration and/or tailing using three methods in various commonly used combinations. The methods were: cutting with a knife, application of constricting rubber rings and using a heated docking iron (tailing only). Behaviour was monitored by quantifying the incidences of restlessness (during the first hour only), normal and abnormal standing/walking, and normal and abnormal lying. Plasma cortisol concentrations were also measured in samples taken at intervals during the 4 hours after treatment. With the knife, abnormal standing/walking predominated throughout the fist 4 hours and beyond, and restlessness was virtually absent. Plasma cortisol concentrations in knife-treated lambs remained above pretreatment values for at least 4 hours. With rings, high restlessness was invariably present during the first 30-45 minutes, and much of the associated standing/walking and lying was abnormal, but all behaviours had returned to control values within 4 hours of treatment, as had the plasma cortisol concentrations. There were no correlations between the incidences of abnormal behaviours and the plasma cortisol concentrations during the first 4 hour after any treatment, except that when abnormal behaviour was present the cortisol concentrations were greater than pretreatment values, and vice versa. Thus, the presence/absence of the abnormal behaviours reported here allowed an assessment of the duration of distress after castration and/or tailing. However, as the behavioural responses to castration and/or tailing were broadly procedure-specific, so that the responses to the knife and rings were not apparently part of the one behavioural continuum, it is argued that the relative intensities of distress caused by the two procedures cannot be assessed from behaviour alone. Rather, reference must also be made to established physiological indices of distress such as plasma cortisol concentration. On that basis, the knife treatments apparently caused greater and more protracted distress responses than did the ring or docking iron treatments, and should therefore be avoided. However, ring-treated lambs, especially those castrated or castrated and tailed apparently experienced distress, so that more benign alternatives to the use of rings should also be sought.

Journal Article↗

PubMed1990

Inhibition of experimentally induced mouse prostatic hyperplasia by castration or steroid antagonist administration.

Mouse prostatic hyperplasia has been induced experimentally by implanting fetal urogenital sinus tissue into the prostate gland of syngeneic mice. We compared the effects of castration and steroid antagonist administration on the growth of the prostate gland during both the early (15 days) and late (30 days) phases of prostatic enlargement. Castration at the time of induction of prostatic hyperplasia is by far the most effective method of inhibiting prostatic overgrowth. A comparison of castration for 7 days with the short-term (7 days) administration of steroid antagonists showed that during the early phase of prostatic enlargement castration is more effective than antiandrogen, which is more effective than 5 alpha-reductase inhibitors. In the late phase of mouse prostatic enlargement, castration for 7 days is less effective than treatment with either antiandrogen or a 5 alpha-reductase inhibitor. Our data indicate that treatment with a combination of an antiestrogen (keoxifene) with a 5 alpha-reductase inhibitor (in particular, 6-methylene progesterone) is the most effective combination for reducing prostatic overgrowth. The antiestrogen (keoxifene) treatment alone was ineffective in both the early and late phases of prostatic overgrowth.

5-alpha Reductase Inhibitors↗

PubMed1993

Differential gonadotropin responses to N-methyl-D,L-aspartate in intact and castrated male rats.

Peripheral administration of N-methyl-D,L-aspartate (NMA), a neuroexcitatory amino acid agonist, probably stimulates LH release through an increase in endogenous LHRH secretion. In the present study, NMA and a potent LHRH antagonist were used to determine the degree to which release of FSH is similarly dependent upon the acute secretion of LHRH. A second aim was to compare responsiveness of LHRH neurons to NMA in castrated and intact male rats. Adult male rats were castrated (n = 10) or sham castrated (n = 11) on the morning of Day 0. After 8 days, rats were fitted with atrial catheters between 0900 and 1200 h; at 2100 h they received s.c. either oil vehicle or 100 micrograms of an LHRH antagonist. Starting at 0900 h on Day 9, 0.5-ml blood samples were collected every 10 min for 3 h. After 1 h of sampling each animal received i.v. 5 mg of NMA in 0.5 ml 0.9% saline. An hour later each rat received i.v. 500 ng of LHRH in 0.5 ml saline. Plasma LH, FSH, and prolactin (PRL) levels were determined by RIA. In the oil-treated sham castrates, mean plasma LH levels were increased by 110% (p < 0.01) within 10 min and remained elevated for 30 min after the injection of NMA. The profile of this LH secretory response was similar to or slightly more robust than endogenous LH pulses observed previously. The NMA-induced LH release was completely blocked by pretreatment with LHRH antagonist. In both oil- and antagonist-treated sham-castrated rats, NMA administration failed to elicit a concomitant increase in plasma FSH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effects of castration and androgen replacement on the hemodynamics of penile erection in the rat.

Previous studies from this laboratory have demonstrated that penile erection in the rat is androgen dependent: 1 wk after castration, there was a significant decline in the magnitude of the intracavernosal pressure (CCP) response during erection induced by stimulation of the autonomic ganglion controlling penile blood flow. The response was altered by vasoactive drugs and appeared to involve nitric oxide synthesis. These earlier studies, however, did not identify the site of androgenic action or the mechanism by which the androgens act. The findings reported here show that even in long-term-castrated animals (up to 7 wk), there remains a rise in CCP in response to ganglionic stimulation, demonstrating that there is an androgen-independent as well as an androgen-dependent portion of the erectile response. Other results show a linear relationship between systemic blood pressure and CCP during erection, although in castrated animals without androgen replacement, the CCP responds less to changes in the systemic pressure than in intact or testosterone-treated animals. This finding could signify a reduced blood inflow and/or an increased blood outflow during erection in the castrated rats. Further studies partially explained the lower erectile pressure by demonstrating that the rate of outflow from the cavernosal spaces was greater in castrated rats than in animals with normal androgen levels. Taken together, these findings show that androgens act to maintain both the inflow and the outflow of blood from the cavernous spaces during erection.

Animals↗

PubMed2000

Failure to achieve castrate levels of testosterone during luteinizing hormone releasing hormone agonist therapy: the case for monitoring serum testosterone and a treatment decision algorithm.

PURPOSE: We report the failure to achieve a castrate level of testosterone associated with 3-month depot luteinizing hormone releasing hormone (LH-RH) agonist therapy, which to our knowledge is a previously unrecognized outcome. MATERIALS AND METHODS: We prospectively enrolled in our study 38 men with prostate cancer on 3-month depot LH-RH agonist therapy. We monitored total serum testosterone and prostate specific antigen every 28 days beginning 90 days after the last depot LH-RH agonist injection. Data were analyzed with castrate testosterone defined as less than 50 and 20 ng./dl. or less. RESULTS: Using the 50 and 20 ng./dl. definitions of castrate testosterone 2 (5%) and 5 (13%) of the 38 men, respectively, failed to achieve castrate testosterone. A patient with a nadir testosterone of 70 ng./dl. subsequently underwent orchiectomy and testosterone decreased to 10 ng./dl. thereafter. CONCLUSIONS: A small but potentially important subgroup of men on depot LH-RH agonist therapy fail to achieve a castrate level of testosterone. Our findings support monitoring testicular response when LH-RH agonist therapy is initiated.

Aged↗

PubMed1992

Castration-resistant secretion in the hamster seminal vesicle does not depend on androgens.

The secretory activity of seminal vesicles (SV) in the castrated hamster was studied by stereological analysis and biochemical approaches following treatment with cyproterone acetate (CPA) and adrenalectomy in order to investigate whether extra-testicular androgens are responsible for castration-resistant protein secretion. Treatment of castrated animals with CPA decreased the size of secretory granules and increased the number of apical granules, though neither the absolute nor the relative volume of all the components analysed was changed. In addition, CPA-treatment increased the amount of protein exocytosed by SV in castrated animals, though total protein synthesis remained unchanged. Adrenalectomy neither suppressed secretion nor induced any further ultrastructural changes in the SV epithelium. Our results demonstrate that secretory activity of the hamster SV following castration is not controlled by extra-testicular androgens and suggest that SV secretory proteins, which are heterogeneous with regard to their sensitivity to androgen withdrawal, might be regulated differentially by androgens.

Adrenalectomy↗