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Self-emasculation and self-castration: immediate surgical management and ultimate psychological adjustment.

Self-emasculation and self-castration most often occur in individuals with known psychiatric disease. In the 3 patients presented 2 performed self-castration apparently while suffering the effects of drugs or alcohol. In both instances apparent psychological adjustment was satisfactory after appropriate psychological care. In the third patient total self-emasculation occurred against the background of known schizophrenia. Immediate surgical management of each patient is presented.

Adult↗

The effects of castration on adrenal testosterone secretion in men with prostatic carcinoma.

Selective adrenal vein catheterization was done on intact and castrated men with prostatic carcinoma. Adrenal to peripheral venous testosterone gradients were observed in all patients, indicating adrenal production of this hormone. No compensatory adrenal production of testosterone was noted during a 17-month period after orchiectomy. The data suggest that the human adrenal in castrates produces testosterone, which may explain why adrenal ablation can offer palliation in some patients with prostatic carcinoma.

Adrenal Glands↗

Castration and pregnancy of rural pigs significantly increase the prevalence of naturally acquired Taenia solium cysticercosis.

Cuentepec is a rural village of central Mexico, where 1300 pigs were bred at the time of the study in conditions that favor Taenia solium transmission. The tongues of 1087 (84%) of these pigs were visually examined and 33% were found to be cysticercotic. Castration of male pigs increased prevalence from 23 to 50% (P < 0.001) and pregnancy in sows also increased their prevalence from 28 to 59% (P < 0.001). Thus, endocrinological conditions characterized by low levels of androgens or high levels of female hormones probably influence the susceptibility of pigs to T. solium cysticercosis as observed in mice infected with Taenia crassiceps. Delaying castration of male pigs and confinement of sows during pregnancy might significantly decrease the prevalence of pig-cysticercosis and help curb transmission without much cost or difficulty.

Animal Husbandry↗

Spontaneous myelofibrosis in castrated and ovariectomized NMRI mice.

The histopathological appearance of myelofibrosis of the bone marrow is described in aged castrated males, ovariectomized females and in male and female control NMRI mice. The highest incidence of the lesion was observed in ovariectomized and female control mice where more than 90% of the animals were affected. The presence of myelofibrosis in the bone marrow of ovariectomized females and castrated males indicates that estrogens may not play a major role in the development of the lesion and other hormonal disturbances must also be considered.

Age Factors↗

Comparison of the effects of stanozolol, oxymetholone, and testosterone cypionate on the sexual behavior of castrated male rats.

In 3 experiments, adult male Long-Evans rats were castrated and treated daily with an anabolic-androgenic steroid (AAS) compound (either stanozolol, oxymetholone, or testosterone cypionate) for 6 weeks. Subjects were assigned to 5 groups that received injections of a high, medium, or low dose of the AAS, testosterone propionate, or the oil vehicle. Stanozolol failed to maintain ejaculation at any dose tested. Although some subjects receiving the low dose of oxymetholone ejaculated, oxymetholone generally failed to stimulate ejaculation above the levels of the oil group. Testosterone cypionate sustained ejaculation at all doses tested. The relative potency of the medium dose of each AAS in the sex accessory tissues was (from most potent to least potent): testosterone cypionate > stanozolol = oxymetholone = oil. Thus, these 3 AAS compounds produced a range of behavioral and endocrine responses in castrated male rats.

Anabolic Agents↗

Castration reduces the effect of serotonin-1A receptor stimulation on prepulse inhibition in rats.

This study examined the interaction between hormones and serotonin-1A (5-HT1A) receptor modulation of prepulse inhibition (PPI) of the acoustic startle response. Male and female rats were gonadectomized; some castrated rats received testosterone- or estrogen-filled implants. Rats were randomly injected with saline or 0.02 or 0.50 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist. All rats showed a dose-dependent disruption of PPI in response to 8-OH-DPAT. In untreated castrated rats, this disruption was significantly reduced (33% compared with 78% in sham-operated rats). Testosterone treatment reversed this reduction, but estrogen was less effective. Ovariectomized and sham-operated rats showed similar PPI in response to 8-OH-DPAT. These data suggest that the effect of 8-OH-DPAT on PPI in male rats depends on circulating hormone levels, particularly testosterone.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

The effects of castration on the induction of experimental gliomas in male rats.

Pellets of 3,4-benzopyrene were implanted into the brain of equal numbers of normal and castrated male rats. The position of the implant was carefully controlled so that it impinged on the mitotically active sub-ependymal plate.A high proportion of glial tumours (77.8%) were induced in normal male rats. The effects of castration were to reduce the incidence of tumoures (50%) and to increase the time interval between implantation and death from cerebral tumour.The implications from these results, as to the possible roles of testosterone, are discussed.

Animals↗

Improving the outcome of patients with castration-resistant prostate cancer through rational drug development.

Castration-resistant prostate cancer (CRPC) is now the second most common cause of male cancer-related mortality. Although docetaxel has recently been shown to extend the survival of patients with CRPC in two large randomised phase III studies, subsequent treatment options remain limited for these patients. A greater understanding of the molecular causes of castration resistance is allowing a more rational approach to the development of new drugs and many new agents are now in clinical development. Therapeutic targets include the adrenal steroid synthesis pathway, androgen receptor signalling, the epidermal growth factor receptor family, insulin growth factor-1 receptor, histone deacetylase, heat shock protein 90 and the tumour vasculature. Drugs against these targets are giving an insight into the molecular pathogenesis of this disease and promise to improve patient quality of life and survival. Finally, the recent discovery of chromosomal translocations resulting in the upregulation of one of at least 3 ETS genes (ERG, ETV1, ETV4) may lead to novel agents for the treatment of this disease.

Antineoplastic Agents↗

The effect of castration on the ribonucleic acid metabolism of an experimental prostatic tumour.

1. The incorporation of [(14)C]phenylalanine into the protein of microsomes obtained from an androgen-dependent transplantable prostatic tumour has been investigated. 2. The incorporation of [(14)C]ATP into the RNA of the nuclei from the same tumour has also been examined. 3. The castration of the host animal depresses the incorporation of both labelled compounds on subsequent incubation in vitro. 4. The uptake of phenylalanine can be markedly stimulated by polyuridylic acid only in tumours obtained from castrated host animals. 5. The tumour RNA-polymerase activity appears to be dependent on the concentrations of androgens in the host animal.

Adenosine Triphosphate↗

The effects of diethylstilboestrol and castration on the nucleic acid and protein metabolism of rat prostate gland.

1. Implantation of diethylstilboestrol pellets into adult male rats brings about similar biochemical changes in the nucleic acid and protein metabolism to castration. 2. The avidity of the prostate for labelled diethylstilboestrol was greater than that of the other organs examined. 3. Uptake of labelled diethylstilboestrol and testosterone into the nuclei of the rat prostate is greater in castrated rats than in controls. 4. Diethylstilboestrol appeared to be associated with the protein and not with the DNA fraction of the nucleus.

Animals↗

Effects of alpha-difluoromethylornithine, an enzyme-activated irreversible inhibitor or ornithine decarboxylase, on testosterone-induced regeneration of prostate and seminal vesicle in castrated rats.

1. Castration of adult rats markedly decreases the amounts of polyamines (putrescine, spermidine and spermine) and of RNA and DNA in the ventral prostate and the seminal vesicle. 2. Daily injections of testosterone propionate to rats castrated 7 days previously increase polyamine and nucleic acid contents more rapidly in the seminal vesicle than in the ventral prostate. 3. After 7 days of androgen treatment, polyamine and nucleic acid contents of the seminal vesicle are significantly higher than those of intact animals. Nucleic acid, but not polyamine, contents return to normal values during the next 4 days of continued treatment. In the prostate, androgen treatment increases polyamine and nucleic acid contents to, but not above, normal values. 4. Repeated doses of alpha-difluoromethylornithine, a potent enzyme-activated irreversible inhibitor of ornithine decarboxylase, totally blocked the testosterone-induced increase of putrescine and spermidine in the ventral prostate and of putrescine in the seminal vesicle. They slowed significantly the accumulation of spermine in the ventral prostate and of spermidine in the seminal vesicle. alpha-Difluoromethylornithine also retarded the testosterone-induced accumulation of RNA in the ventral prostate. However, no clear correlation was apparent between accumulation of polyamines and of nucleic acids in the two organs. 5. alpha-Difluoromethylornithine markedly slows the testosterone-induced weight gain of the prostate, but not of the seminal vesicle. Cytological studies suggest that this effect on the prostate is due to inhibition of the androgen-induced restoration of the secretion content of prostatic acini.

Animals↗

Differential effects of 2-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) on the testosterone-induced growth of ventral prostate and seminal vesicles of castrated rats.

2-Difluoromethylornithine totally prevented any increases in putrescine and spermidine concentrations in the ventral prostate of castrated rats during a 6-day testosterone treatment. Prostatic ornithine decarboxylase activity was inhibited by 80%, whereas S-adenosylmethionine decarboxylase was stimulated by more than 9-fold. In seminal vesicle, the inhibition of putrescine and spermidine accumulation, as well as of ornithine decarboxylase activity, was only minimal, and no stimulation of S-adenosylmethionine decarboxylase was observed. Administration of methylglyoxal bis(guanylhydrazone) to castrated androgen-treated rats resulted in a marked increase in concentrations of all prostatic polyamines. Prostatic ornithine decarboxylase activity was nearly 2 times and adenosylmethionine decarboxylase activity 9 times higher than that of the testosterone-treated animals. In contrast with ventral prostate, methylglyoxal bis(guanylhydrazone) treatment inhibited moderately the accumulation of spermidine and spermine in seminal vesicle, although both ornithine decarboxylase and S-adenosylmethionine decarboxylase activities were stimulated. Difluoromethylornithine inhibited significantly the weight gain of ventral prostate, but methylglyoxal bis(guanylhydrazone) produced a substantial increase in prostatic weight. These changes were largely due to the fact that the volume of prostatic secretion was greatly decreased by difluoromethylornithine, whereas methylglyoxal bis(guanylhydrazone) increased the amount of secretion. Treatment with difluoromethylornithine strikingly increased the methylglyoxal bis(guanylhydrazone) content of both ventral prostate and seminal vesicle, but even under these conditions the drug concentration remained low in comparison with other tissues. The results indicate that a combined use of these two polyamine anti-metabolites does not necessarily result in a synergistic growth inhibition of the androgen-induced growth of male accessory sexual glands.

Animals↗

Brain aromatase in control versus castrated Norway Brown, Sprague-Dawley and Wistar adult rats.

Brain aromatase cytochrome P450 converts androgens to estrogens that play a critical role in the development of sexually dimorphic neural structures, the modulation of neuroendocrine function(s), and the regulation of sexual behavior. We characterized the influence of surgical castration on brain aromatase in Norway Brown and Wistar adult rats and compared their responses to Sprague-Dawley rats that were surgically or biochemically castrated (with flutamide, a known androgen receptor blocker). Aromata enzyme activity was measured by the tritiated water release assay in the medial basal hypothalmus/preoptic area (MBH/POA) and amygdala brain regions. The present results demonstrate that independent of the rat strain examined, MBH/POA aromatase is regulated by androgens (in Sprague-Dawley, Norway Brown and Wistar males). However, intact Wistar animals displayed significantly higher MBH/POA aromatase levels compared to Sprague-Dawley control values. Conversely, in the amygdala region, there was an apparent lack of androgen hormone action upon aromatase enzyme activity in some of the rat strains tested. The importance of brain aromatase regulating estrogen biosynthesis and influencing brain development and function is covered.

Amygdala↗

The effect of castration and androgen treatment on glomerular volume in mice.

The mouse kidney is specially responsive to the withdrawal or administration of androgens. Castration markedly reduces renal weight in male mice, whereas androgen treatment restores normal kidney size. The present study demonstrates that these changes in whole kidney size are accompanied by parallel changes in total glomerular volume. The results indicate that the individual glomeruli change their volume during the experiments. The observed changes in the kidney weight and total volume of glomeruli after castration did not affect the plasma level of creatinine. Smaller kidney with less total volume of glomeruli can preserve internal environment.

Androgens↗

Relationship between release of LH and incorporation of tritiated thymidine in the anterior pituitary gland of the castrated female rat.

Castration of female rats during diestrus increases the concentration of circulating LH from days 3 and the incorporation of 3H thymidine into pituitary DNA from day 5. Both effects are completely abolished by the administration of dihydrotestosterone. Although the i.v. injection of LHRH markedly enhances the concentration of LH in serum, it does not modify the incorporation of 3H thymidine into pituitary DNA. Castration might produce a maximal stimulation in 3H thymidine incorporation and a further stimulation of LH release with LHRH is unable to enhance the incorporation of the radioactive precursor. The results suggest a relationship between LH secretion and DNA synthesis in the pituitary gland of the rat.

Animals↗

Further data on the androgenic dependency of the skeletal musculature: the effect of prepubertal castration on the structural development of the skeletal muscles.

The effect of prepubertal castration was investigated in the soleus, semimembranosus and levator ani muscles of rat, using light and electronmicroscopic morphometric methods. After castration the semimembranosus and the levator ani muscles showed significant morphometrical alterations. The weight of the muscles diminished, the diameter of the white fibers decreased. The ultrastructure of these muscles showed a well expressed myofibrillar atrophy. The changes in the semimembranosus muscle were less severe. The slow oxidative soleus muscle did not show any similar alterations. The changes in the levator ani and semimembranosus muscles could be prevented or moderated by testosterone substitution.

Animals↗

Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: role of vascular endothelial growth factor.

The sequence of events that leads to tumor vessel regression and the functional characteristics of these vessels during hormone-ablation therapy are not known. This is because of the lack of an appropriate animal model and monitoring technology. By using in vivo microscopy and in situ molecular analysis of the androgen-dependent Shionogi carcinoma grown in severe combined immunodeficient mice, we show that castration of these mice leads to tumor regression and a concomitant decrease in vascular endothelial growth factor (VEGF) expression. Androgen withdrawal is known to induce apoptosis in Shionogi tumor cells. Surprisingly, tumor endothelial cells begin to undergo apoptosis before neoplastic cells, and rarefaction of tumor vessels precedes the decrease in tumor size. The regressing vessels begin to exhibit normal phenotype, i.e., lower diameter, tortuosity, vascular permeability, and leukocyte adhesion. Two weeks after castration, a second wave of angiogenesis and tumor growth begins with a concomitant increase in VEGF expression. Because human tumors often relapse following hormone-ablation therapy, our data suggest that these patients may benefit from combined anti-VEGF therapy.

Androgens↗

Effects of zinc on intact and castrated cockerels.

1. Fourteen-week-old intact and castrated cockerels (White Leghorn) were injected intramuscularly with zinc (100 micrograms/kg body weight) as zinc ammonium sulphate solution once daily for 4 weeks and the effects on testes, pituitary and adrenal glands investigated histologically. 2. In intact cocks zinc decreased testes weight significantly, inhibited spermatogenesis and disturbed testicular hormone production. There was an increase in pituitary gonadotrophic cell activity, perhaps an indication of feed-back response to low concentration of testicular hormone. Cortical and medullary cells of the adrenal glands showed signs of activation. 3. No discernible effects of zinc injection on pituitary and adrenal cells of castrates were observed. This may reflect a decrease in pituitary and adrenal responsiveness to repeated stimulation with zinc. 4. The results indicate that the effectiveness of a given dose of zinc was dependent on the physiological condition of the cockerels and the effective site of zinc action was centred in the testes.

Adrenal Glands↗