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PubMed1991

Insulin-like growth factor-I concentrations in plasma of intact and castrated male and female cattle at four ages.

The influence of age, sex and castration on plasma concentrations of insulin-like growth factor-I (IGF-I) and other metabolic hormones related to growth was studied in cattle. Plasma was sampled from bulls, steers, heifers, and ovariectomized heifers at 20-min intervals for 12 hr at 5, 8, 12, and 15 mo of age. Plasma samples from each animal taken during each 12-hr period were composited for analysis of IGF-I, testosterone, total estrogens, thyroxine, triiodothyronine, insulin, and glucose. The mean plasma IGF-I concentration in all cattle increased from 61.6 to 158.6 ng/ml as the animals aged (p less than .01). Over all ages, bulls had greater concentrations of IGF-I than steers, heifers, or ovariectomized heifers (P less than .01). Bulls also had higher concentrations of testosterone (P less than .01) and total estrogens (P less than .01). Triiodothyronine concentration was greater in ovariectomized heifers than in bulls (P less than .01) or steers (P less than .05). Females had higher concentrations of thyroxine than males (P less than .01). Concentrations of triiodothyronine in the cattle were greater (P less than .01) during the winter and early spring as compared with the summer. Concentrations of insulin and glucose were not influenced by sex or castration; however, insulin increased in all cattle with age (P less than .01). The mean increase in IGF-I concentration with age within each of the four groups was associated with an increase in concentration of plasma insulin but the differences due to sex were not related to differences in insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Pathophysiology of bone loss in castrated animals.

The pathophysiology of bone loss in castrated animals is reviewed. Both male and female rats rapidly lose metaphyseal trabecular bone from the tibia and the femur due to an imbalance between bone resorption and bone formation. The aetiology of sex hormone deficiency-induced bone loss is not fully understood. It seems unlikely that the bone loss is due to changes in the circulating levels of the calciotropic hormones or to an increase in the spontaneous release from peripheral blood monocytes of the bone resorption stimulating cytokine IL-1. Changes in the sensitivity of bone of castrated rats to calciotropic hormones may play a role as well as the lack of direct stimulatory effects of gonadal oestrogens and androgens on bone cells. In addition several data indicate that prostaglandins may be involved.

Animals↗
PubMed2005

Effect of testosterone on functional recovery in a castrate male rat stroke model.

Both increased and decreased testosterone levels have been reported to correlate with poor outcome after acute ischemic stroke. The present study focused on the role of testosterone during recovery from neurological deficits in a rat focal ischemia model. Castrate male rats were subjected to behavioral tests after 90 min of middle cerebral artery occlusion (MCAO). On day 7 post-MCAO, neurological deficit-matched rats were assigned to a treatment group implanted with subcutaneous testosterone pellets or a control group implanted with sham cholesterol pellets. After 4 weeks post-MCAO, the average infarct volume was not significantly different between the two groups. Rats in the testosterone group demonstrated significantly earlier improvement in neurological deficits and shortened latency of adhesive tape removal compared with the control group as analyzed by Wilcoxon signed ranks test. Walking on parallel bars improved in both groups with a trend towards early recovery observed in the testosterone group. Biased left body swings persisted during the test period in both groups post-MCAO. Serum testosterone was within physiological levels in the treatment group but was not detectable in the control group by radioimmunoassay. GAP-43 and synaptophysin expression did not differ between groups. Less GFAP expression and reactive astrocyte hypertrophy were found around the infarct area in testosterone-treated rats compared with control rats. In conclusion, testosterone replacement post-MCAO accelerated functional recovery in castrate rats, suggesting a potential therapeutic role for testosterone replacement in stroke recovery.

Androgens↗
PubMed2006

Early postnatal castration affects thymic and thymocyte noradrenaline levels and beta-adrenoceptor-mediated influence on the thymopoiesis in adult rats.

The interactions among the nervous, endocrine and immune system were studied by examining: i) thymic and thymocyte catecholamine levels in adult rats castrated (Cx) at postnatal day 3 and ii) effects of 14-day-long propranolol (P) treatment on main thymocyte differentiational molecule expression in adult non-Cx and Cx rat. The results demonstrated that castration in early postnatal period lowers levels of both neurally- and thymocyte-derived noradrenaline in adult rats, and thereby diminishes beta-adrenoceptor-mediated fine tuning of the T-cell differentiation/maturation. In non-Cx rats P affected TCRalphabeta-dependent stages of thymocyte differentiation/maturation decreasing frequency of CD4+8+ double positive (DP) TCRalphabeta(low) cells entering selection processes and increasing relative number of positively selected DP TCRalphabeta(high) (most likely due to an increased thymocyte surface density of Thy-1 that is involved in negative control of TCRalphabeta-mediated signaling/selection thresholds) and the most mature CD4+8- TCRalphabeta(high) cells (including CD4+25+ regulatory cells). However, in Cx rats P failed to produce any significant changes in thymocyte subset composition.

Adrenergic beta-Antagonists↗
PubMed2004

Phosphorylation of p70s6 kinase is implicated in androgen-induced levator ani muscle anabolism in castrated rats.

Androgens are known to increase muscle mass, strength and muscle protein synthesis. However, the molecular mechanisms by which androgens regulate skeletal muscle development remain poorly understood. The ribosomal protein kinase p70(s6k) is a regulator of ribosome biogenesis and plays an important role in the regulation of growth-related protein synthesis. The phosphorylation of p70(s6k) has been implicated in load-induced skeletal muscle hypertrophy. In the current study, we determined the effect of DHT on the phosphorylation of p70(s6k) in the androgen-sensitive levator ani muscle of castrated rats. DHT induced a rapid increase in the phosphorylation of p70(s6k), which was detectable within 6 h after a single injection. Interestingly, DHT-induced phosphorylation of p70(s6k) occurred only in androgen-sensitive muscles, but not prostate and seminal vesicle. Co-administration of flutamide, an AR antagonist, inhibited DHT-induced p70(s6k) phosphorylation. While serum IGF-I levels were not changed by DHT treatment, IGF-I gene expression levels increased and the mRNA levels of IGFBP3 and IGFBP5 were suppressed in the LA muscle after DHT replacement in castrated rats. These results suggest that the phosphorylation of p70(s6k), likely via the IGF-I pathway, may play an important role in androgen-induced skeletal muscle hypertrophy.

Androgen Receptor Antagonists↗
PubMed2005

Evaluation of estrogenic and androgenic activity of butylated hydroxyanisole in immature female and castrated rats.

We evaluated the estrogenic and androgenic activity of butylated hydroxyanisole (BHA) using immature rat uterotrophic assay and Hershberger assay. To investigate (anti-) estrogenicity, BHA alone or with 17beta-estradiol was administered to 20-days-old immature female rats for three consecutive days. Absolute and relative uterine weights were significantly decreased by BHA (50, 100, 250, 500 mg/kg) alone and 17beta-estradiol-stimulated weights of uterine and vagina were also decreased by BHA (500 mg/kg), while uterine epithelial cell height was not affected. In Hershberger assay, BHA alone or with testosterone propionate (TP) was administered daily to 51-days-old castrated male rats for 10 days. BHA alone or with testosterone propionate (TP) caused no significant effect on androgen-dependent accessory sex organ weights; seminal vesicle/coagulative glands, glans penis, Cowper's gland, ventral prostate gland and levator ani plus bulbocarvernosus muscle. Although, the relative weight of ventral prostate gland was increased by the co-treatment of BHA 250 mg/kg with TP 0.4 mg/kg compared to that of TP alone, the relative and absolute weights of other androgen-dependent organs and absolute and formalin-fixed ventral prostate gland weight showed no changes. Our studies suggest that BHA have anti-estrogenic activity for the decrease of uterine weight in immature female rat but have negligible effect on the androgenic activity in castrated male rats.

Animals↗
PubMed2003

Use of nomograms for predicting survival in patients with castrate prostate cancer.

Given the heterogeneity of prognoses in patients with castrate metastatic prostate cancer, the ability to accurately predict survival is vital for optimal patient counseling, selection of treatments, clinical trial design, and interpretation of clinical data. Over the past 20 years, several prognostic models have been developed in an attempt to refine the clinician's predictive ability. Early models were based on patients with more advanced disease. They included variables that are no longer regularly encountered today and involved cumbersome calculations that were not practical for everyday use in the clinic. Recently, 2 point-based nomograms have been developed based on pretreatment variables measured on a routine basis. These models provide a user-friendly format in which to make sophisticated predictions of survival. These models have improved our ability to predict the outcomes of patients with castrate metastatic disease. However, further work to identify novel prognostic markers to improve the accuracy of these predictions is needed.

Adenocarcinoma↗
PubMed2003

Effects of testosterone metabolites on copulation and medial preoptic dopamine release in castrated male rats.

The medial preoptic area (MPOA) is an important integrative site for male sexual behavior. Dopamine (DA) is released in the MPOA of male rats shortly before and during copulation. The recent presence of testosterone (T) may be necessary for this precopulatory increase in release. Previously, the postcastration loss of copulatory ability mirrored the loss of the DA response to an estrous female, and the restoration of copulation with exogenous T was concurrent with the reemergence of this DA response. The present study investigated the effectiveness of the two major metabolites of T in maintaining copulation and basal and female-stimulated DA levels. Adult male rats were castrated and received daily injections of estradiol benzoate (EB), dihydrotestosterone benzoate (DHTB), EB + DHTB, testosterone propionate (TP), or oil vehicle for 3 weeks. Microdialysis samples were collected from the MPOA during baseline conditions, exposure to an estrous female behind a barrier, and copulation testing. EB + DHTB- and TP-treated animals had normal basal DA levels and showed a precopulatory DA response, and most copulated normally. EB-treated castrates had high basal DA levels, but failed to show a female-stimulated increase; most intromitted, but none ejaculated. DHTB- and oil-treated groups had low basal levels of extracellular DA that did not increase during copulation testing; most failed to mount and none ejaculated. These results suggest that E maintains normal basal levels of extracellular DA in the MPOA, which are sufficient for suboptimal copulation, but that androgen is required for the female-stimulated increase in DA release and for facilitation of ejaculation.

Analysis of Variance↗
PubMed2003

Glycosaminoglycan profile in bladder and urethra of castrated rats treated with estrogen, progestogen, and raloxifene.

OBJECTIVE: This study was undertaken to evaluate the action of conjugated equine estrogens alone, medroxyprogesterone, the combination of these estrogens with progestogens, and of raloxifene on the glycosaminoglycan profile in the bladder and urethra of adult oophorectomized rats in comparison with noncastrated rats. STUDY DESIGN: Sixty adult rats, of which 50 were submitted to bilateral oophorectomy, were studied. After 4 days, the latter were assigned to five groups of 10 animals each. For 30 consecutive days the following treatments were given: group 1, conjugated equine estrogens; group 2, conjugated equine estrogens combined with medroxyprogesterone acetate; group 3, medroxyprogesterone; group 4, raloxifene; and group 5, placebo. Thereafter the bladders and urethras of the animals were removed, processed to yield a dry powder of which the sulfated glycosaminoglycan content was determined by densitometry after agarose gel electrophoresis and that of hyaluronic acid by a fluorimetric assay. RESULTS: Glycosaminoglycans found in the bladder and urethra were dermatan sulfate, heparan sulfate, and hyaluronic acid. In the bladder, hypoestrogenism or replacement with estrogens led to a lower sulfated glycosaminoglycan content. Replacement with estrogens and/or medroxyprogesterone reverted this effect. Hypoestrogenism decreased the dermatan sulfate/heparan sulfate ratio and reduced hyaluronic acid content. Estrogen therapy reverted this alteration and medroxyprogesterone addition annulled the estrogenic effect. In the urethra, castration did not alter hyaluronic acid content and sulfated glycosaminoglycan content, but raloxifene decreased the latter. CONCLUSION: Castrated rats had a decrease in sulfated glycosaminoglycans and hyaluronic acid content in the bladder. Hormonal replacement altered the quantity and quality of glycosaminoglycans. In the urethra, raloxifene reduced sulfated glycosaminoglycans.

Analysis of Variance↗
PubMed2000

Host castration by Aphidius ervi venom proteins.

The braconid Aphidius ervi Haliday (Hymenoptera, Braconidae) is an endophagous parasitoid of the pea aphid, Acyrthosiphon pisum (Harris) (Homoptera, Aphididae). Parasitized host aphids show different degrees of castration, a response that is total when parasitoid oviposition takes place in first instar hosts. Deleterious effects on the host reproductive system are already evident by 24h following parasitization, before egg hatching. The effect of parasitoid venom on A. pisum ovaries has been studied by performing microinjections in non-parasitized host aphids and observing the cellular alterations of the apical germaria of ovarioles. Venom injection reproduced the same alterations observed in parasitized aphids, while injections of saline solution did not induce any detectable change. By 24h, the germarial cells of both venom-treated aphids and parasitized aphids showed the absence of the nucleolus and of electron-dense material around the nucleus, frequently referred to as "nuage material". By 48h more evident signs of degeneration were observed, suggesting the possible occurrence of apoptosis. The bioactive component of the venom was both heat- and protease-sensitive. The activity was found in purified fractions that were highly enriched in two proteins with an approximate molecular mass of 21kD and 36kD, respectively. These macromolecules are the most abundant components of A. ervi venom and, unlike many venom proteins of studied parasitic Hymenoptera, are not glycosylated and appear to be subunits of an oligomeric protein. The adaptive significance of host castration is discussed.

Journal Article↗
PubMed1994

Prevalence and duration of hot flushes after surgical or medical castration in men with prostatic carcinoma.

A total of 77 men with prostatic carcinoma treated with orchiectomy or a gonadotropin releasing hormone analogue before September 1987 underwent evaluation by a questionnaire regarding vasomotor symptoms. Answers were received from 84% of the patients. Of 63 patients 43 (68%) reported hot flushes during treatment, while 30 (48%) still had flushes 5 years after treatment. Of the latter 30 patients 28 (median 7.6 years after treatment) had vasomotor symptoms at the time of the study. Only 13 of 43 men with vasomotor symptoms after the start of treatment had relief 5 years later. At the time of the study 13 of 30 patients (more than 40%) still had flushes 8 years after castration. Most men reported that the flushes presently had the same frequency and duration as when they started therapy. Contrary to the general belief that the symptoms disappear with time, our study highlighted a long persistence of hot flushes after castration.

Aged↗
PubMed2002

Regulation of the expression of protein kinase C isoenzymes in rat ventral prostate: effects of age, castration and flutamide treatment.

Protein kinase C (PKC) isoenzymes are involved in cell function, growth, apoptosis and neoplastic transformation in the prostate gland. We detected by means of Western blot the expression of the classical alpha and beta1, the novel epsilon and the atypical zeta isoforms of PKC in ventral prostates from rats with different extents of plasma testosterone levels and/or androgen imprinting on the gland. The expression of the four isoforms decreased in 5-day castrated rats showing apoptotical regression of the gland and a drastic reduction of circulating testosterone. However, the expression of PKC isoenzymes (alpha, beta1, epsilon ) increased in prostates from pubertal (35-days old) rats that are characterized by relatively low but extremely bioactive testosterone plasma levels. Treatment of adult rats for 14 days with flutamide (daily s.c. injection of 15 mg/Kg B.W.) resulted in increased expression of the four isoenzymes; it occurred in the presence of increased (normal rats) or drastically reduced (rats castrated after 9 days of flutamide administration) levels of plasma testosterone conceivably through a direct effect of this nonsteroidal antiandrogen on prostate cells. Measurements of PKC(alpha) activity were in agreement with the observations on protein expression and showed that flutamide (that is extensively used in the treatment of advanced prostate cancer) elicits some impairment in the mechanisms of translocation of this isoform from the cytosol to the membrane. Thus, in addition to the possibility of direct effects of flutamide upon the rat prostate, we present evidence that the levels of circulating androgens and/or their bioactivity in the gland regulate the expression of various important PKC isoforms.

Aging↗
PubMed1997

Neonatal castration and adult responsiveness to testosterone in male rats: an interstrain comparison.

We have previously demonstrated that the spontaneously hypertensive rat (SHR) has a lower central nervous responsiveness to testosterone than its normotensive counterpart the Wistar-Kyoto rat (WKY). The adult psychoendocrine response capacity depends on a neonatal testosterone surge. On that basis, we compared the effects of neonatal endocrine manipulation on the adult responsiveness to testosterone in the SHR, WKY, and yet another breed of Wistar (Wi) male rats. Interstrain differences in testosterone-induced copulatory behavior at three different doses of testosterone propionate (TP) were investigated. Neonatal treatments were as follows: TP (0.25 mg/animal) given on postnatal days (PND) 0, 2, and 4 (SHR and Wi only) or castration PND 0, 10, or 50. Neonatal TP treatment impaired copulatory performance in the adult SHR but not in the Wi. Neonatal castration improved the responsiveness to TP in the SHR but less so in WKY, whereas no evident effects were seen in the Wi. No significant interstrain differences in plasma testosterone were observed 2, 6-12, or 24 h postpartum. The demonstrated interstrain differences suggest not only that the adult responsiveness to testosterone is established on the basis of the neonatal gonadal secretion as such but that this secretion is kept to an optimal level with respect to subsequent hormone-sensitive mechanisms.

Animals↗
PubMed1996

Effect of flutamide and flutamide plus castration on prostate size in patients with previously untreated prostate cancer.

OBJECTIVES: Transrectal ultrasonography (TRUS) was used in previously untreated men with prostate cancer undergoing hormonal therapy to provide objective observations on the decrease in prostate size and to assess the usefulness of prostate size in estimating treatment response. METHODS: In this retrospective study, 31 patients with previously untreated prostate cancer (Stage T1c to D2) who received hormonal therapy (flutamide, n = 18; flutamide plus castration, n = 13) were followed with serial estimations of prostate size by TRUS and by serum prostate-specific antigen (PSA). RESULTS: In both treatment groups, the major decreases in prostate size were noted within the first 6 months of therapy, whereas further follow-up examinations failed to show statistically significant changes. Prostate size decreased by 48% in men treated with flutamide, whereas those treated with flutamide plus castration showed a statistically significant greater decrease, mean of 56% (P < or = 0.01). Six patients (33%) in the flutamide group and 5 (38%) men in the total androgen deprivation group ultimately failed therapy as indicated by a rising PSA level. Only 55% (n = 6) of the patients who progressed showed an increase in prostate size. CONCLUSIONS: Total androgen deprivation in comparison to flutamide alone caused a larger reduction in prostate size. As a marker of hormonal failure, a rising PSA was more sensitive than an increase in prostate size.

Aged↗
PubMed2002

Modulatory activity of sildenafil on copulatory behaviour of both intact and castrated male rats.

The first experiment of the present study investigates the effects induced by sildenafil (1 or 10 mg/kg po) on the copulatory behaviour of intact male rats, categorized, on the basis of seven consecutive mating pretests, as sluggish or normal ejaculators (SE or NE, respectively). The data obtained show that sildenafil modifies both sexual arousal and the ejaculatory mechanisms of copulation, diminishing ejaculation latency in both categories and increasing copulatory efficacy in SE rats; in addition, it reduced the inter-intromission interval in both SE and NE animals and the post-ejaculatory interval only in SE animals. The second experiment, conducted on rats 3 weeks after their castration, shows that sildenafil alone (1 or 10 mg/kg) did not modify copulatory failure. However, 3 months after castration, and 24 h after the last injection of testosterone (25 microg/kg sc) given twice weekly for 4 weeks, sildenafil (1 or 10 mg/kg) ameliorated rat copulatory performance.

Animals↗
PubMed2002

Prognostic factor analysis in patients with advanced prostate cancer treated by castration plus anandron or placebo: a final update.

PURPOSE: Different outcome results have been published in trials comparing maximal androgen blockade (MAB) with chemical or surgical castration alone. The conflicting results could be explained by the fact that patients were included with different prognostic factors. In this new analysis of the Anandron European Study, independent prognostic factors have been evaluated in order to identify those which could influence the study outcome and the impact of the treatment. MATERIAL AND METHODS: 399 out of 457 patients recruited in this study were divided in a good or poor prognostic group depending on the presence of two or more poor prognostic factors, these were pain requiring treatment, >5 bone metastases, hydronephrosis, and alkaline phosphatase >2 ULN. RESULTS: When expressed as a percentage, the improvement in time to progression, overall and cancer specific survival in the Anandron treated patients was identical in both groups. In absolute terms this improvement, however, was greater in the good prognostic group. CONCLUSION: In comparison with surgical castration MAB using Anandron, in patients with metastatic prostate cancer improves the time to objective progression, overall and cancer specific survival, irrespective of certain poor prognostic factors.

Aged↗
PubMed1998

Efficacy of dicyclanil in the prevention of screwworm infestation (Cochliomyia hominivorax) in cattle castration wounds.

A field trial was carried out during summer 1996 in a commercial beef cattle farm located in the central area of Argentina (30 degrees 16'S, 60 degrees 30'W) to evaluate the efficacy of a new insect growth regulator material (dicyclanil) in the prevention of myiosis caused by screwworm (Cochliomyia hominivorax) larvae. Forty bull calves (Bos indicus x Bos taurus), 5 to 6 months old were allocated by ranked paris to a control (G.1) and a treated group (G.2) of the same number of animals. On day 0, all experimental animals were surgically castrated and calves of group 2 were treated topically with 20 ml as a single dose of a ready-to-use formulation containing 5% w/v dicyclanil. Inspections for screwworm larva infestation were carried out on days 4, 8, 12, 16, 19, 23 and 25 after castration. The incidence of egg masses on the scrotal wounds evidenced a similar challenge for all groups (P > 0.05 chi(2)). However, 16 animals of G.1 (80%) and only one of G.2 (5%) developed active myiosis, respectively. This difference was significant (P=0.003 X(2)).

Administration, Topical↗
PubMed1988

Complications of castration and ovariectomy.

This article discusses the complications of castration and ovariectomy and their treatment and prevention. These two procedures were chosen because castration is the most common surgical procedure performed by the equine practitioner and ovariectomy is associated with a high number of complications.

Animals↗