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PubMed1994

Prostatic tumor regrowth after initially successful castration therapy may be related to a decreased apoptotic cell death rate.

Castration of rats transplanted with the androgen-sensitive Dunning R3327-PAP prostatic tumor results initially in a reduction of tumor growth, but after some time, some of the tumors start to grow again. The relapsed, androgen-insensitive PAP tumor shows a dedifferentiated morphology. In the present study, we examined whether this androgen-independent tumor regrowth was due to an increased cell proliferation rate or to a reduction of the number of tumor cells dying by apoptosis. Nine rats (with 18 tumors) were castrated and followed for 16 to 20 weeks. Six of the tumors increased their volume markedly (relapsed), while 12 remained relatively stable (nonrelapsed). The mitotic index and apoptotic index for epithelial cells were examined by light microscopy. Tumor growth rate correlated negatively both to the apoptotic index identified by morphological criteria (RS = -0.82; P < 0.0001) and to the apoptotic index identified by in situ end labeling (RS = -0.83; P < 0.0001). The tumor growth rate percentage did not correlate to the mitotic index, and it was negatively correlated (RS = -0.62; P < 0.01) to the number of cells immunostained for proliferating cell nuclear antigen. It is suggested that one initial event during the androgen-independent prostatic tumor regrowth in the PAP relapse model might be a reduction of the number of tumor cells being depleted by apoptosis, rather than an increase of cell proliferation rate.

Animals↗

PubMed1993

Autoradiography of pituitary cells stimulated by castration or methimazole feeding.

It has been argued that the increase in size of the pituitary of castrated cockerels is due to hypertrophy of gonadotropic cells, some of which have been converted from other pituitary basophils. A counter argument could maintain that new gonadotropes are recruited from chromophobes that are replaced by mitotic division of undifferentiated cells. Since mitosis requires thymine for DNA replication, labelled thymine (H3-thymidine) incorporated in DNA identifies new cell formation. On this basis, the chicken pituitary does not produce enough new cells to account for the size differences associated with castration or methimazole treatment.

Adrenocorticotropic Hormone↗

PubMed1993

Polychlorinated biphenyl-induced immune suppression: castration, but not adrenalectomy or RU 38486 treatment, partially restores the suppressed cytotoxic T lymphocyte response to alloantigen.

The cytotoxic T lymphocyte (CTL) response to allogeneic P815 tumor in C57bl/6 mice is dose-dependently suppressed after treatment with 3,3',4,4',5,5'-hexachlorobiphenyl (HxCB). Elevation of plasma corticosterone (CS) is also observed coincident with CTL suppression. Because immune suppression is inducible by glucocorticoid administration, the role of elevated CS was investigated as an indirect mechanism of HxCB-induced immunotoxicity. In multiple experiments, HxCB treatment (10 mg/kg b.w.) consistently reduced CTL activity by 70 to 85% in male mice. Adrenalectomy failed to alter the suppression of CTL activity by HxCB. However, the mortality rate was high (> or = 70%) in these experiments and plasma CS elevation persisted in HxCB-treated adrenalectomy survivors. Therefore, the use of adrenalectomized mice was inadequate to determine whether CS elevation leads to CTL suppression after HxCB treatment. Daily administration of the glucocorticoid receptor antagonist 17-beta-hydroxy-11-beta-(4-dimethylaminophenyl)-17-alpha-(propanyl )-estra- 4,9-dien-3-one (RU 38486) (150 mg/kg b.w., p.o.) also failed to alter the suppression of CTL activity in HxCB-treated mice; however, spleen cellularity was significantly increased, suggesting functional GCR antagonism. Male mice were more sensitive to HxCB-induced CTL suppression than female mice, and HxCB-induced plasma CS elevation was greater in male mice. Castration failed to reduce the elevation of plasma CS in HxCB-treated male mice. However, castration partially alleviated CTL suppression in HxCB-treated male mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1993

Functional ectopic interstitial cell tumor in a castrated male cat.

A 12-year-old male cat that had been castrated at 6 months of age was examined to determine the cause of urine spraying of 2 years' duration. The cat had acquired physical characteristics of a sexually intact male, and its serum testosterone concentration was greater than values expected for a castrated cat. Administration of a variety of medications did not halt urine spraying. At necropsy, an interstitial cell tumor was found in a remnant of a spermatic cord.

Animals↗

PubMed1993

Acquired arteriovenous fistula secondary to castration in a dog.

A 6-year-old castrated male Basset Hound was examined because of a 1-year history of a pulsating mass in the right inguinal region. The pulsatile mass was diagnosed as an arteriovenous fistula by physical examination and angiography. Surgical exploration revealed that the right testicular artery and vein, the artery of the ductus deferens, and the cremasteric artery were involved in the fistula. The fistula was believed to have developed secondary to castration performed at 6 months of age. The mass and associated vessels were completely excised and signs of recurrence were not observed 13 months after surgery.

Animals↗

PubMed1995

Thymic weight changes and endocrine relationships during maturation in cattle: effects of age, sex, and castration.

Elucidation of cause and effect relationships between gonadal and thymic function can be particularly challenging due to the complexity of interactions among various hormones on thymic function, many of which are largely unknown. To monitor gonadal-thymic interaction with the endocrine changes associated with maturity, bulls, steers, heifers, and ovariectomized heifers were slaughtered at 4, 6, 10, 12, or 14 months of age (n = 5-7/sex/age). Steers and ovariectomized heifers were castrated before 1 week of age. Thymic weights were increased in castrated animals as early as 4 months of age (p < 0.01), and differences were more pronounced in males. Thymic secretory peptide, thymosin beta4, increased up to six months of age in all groups (p < 0.05) and then decreased with age, similar to the pattern of growth hormone. Prepuberal testosterone concentrations increased to 10-12 months of age and then decreased in both bulls and heifers (p < 0.05), coordinate with decreases of thymosin beta4 at 10 months of age. Growth hormone concentrations increased up to 6 months of age in all groups (p < 0.01) and then declined. Concentrations of prolactin peaked at 10 months of age (p < 0.01) but were not different between groups. Relationships of luteinizing hormone (LH) were highly related to thymosin beta4 changes in heifers during maturation. Changes of thymosin beta4 and LH were coordinate in ovary-intact heifers and inversely related in ovariectomized heifers. Gonadal effects on thymic weight were evident as early as 4 months of age, and no abrupt declines in thymic weight were detected at puberty.

Age Factors↗

PubMed1995

The Little Mermaid: an icon of woman's condition in patriarchy, and the human condition of castration.

Hans Christian Andersen's story 'The Little Mermaid' is read as a creation myth and a metaphor for woman's condition in patriarchy, broadly conceptualised within a Lacanian framework. In the first part, the psychoanalytic concept of castration (broadly conceptualised as containing any existential severance which forms the basis for sexual difference and subjectivity) is utilised to argue that the myth is about a construction of (mostly female) subjectivity through a series of separations or splits: (1) birth, (2) growing up, (3) desire and (4) death. Birth and death are read as representing real separations. Growing up is read as structured around a symbolic castration of tongue and voice, while desire is read as structured around lack. In the second part the ideological implications of Disney's adaptation of the original for its symbolic status are explored. It is argued that by simplifying and externalising internal complex conflicts in the Andersen story, Disney's version reduces the myth to a fairy tale, and reproduces the ideology of romantic love.

Fantasy↗

PubMed1996

Laparoscopic methods for castration of equids.

OBJECTIVE: To evaluate 2 laparoscopic techniques for castration of horses. DESIGN: Prospective, randomized trial. ANIMALS: 6 sexually intact male ponies. PROCEDURE: Ponies were anesthetized and placed in dorsal recumbency. By means of restricted randomization, 1 testis in each pony was selected to undergo in situ destruction (i.e., vascular cauterization and ligation with the testis left in situ); the other testis was pulled back into the abdomen and removed. Baseline and stimulated testosterone concentrations were determined preoperatively and postoperatively. After euthanasia, the in situ testes were examined histologically. RESULTS: There were no surgical complications. In all ponies, postoperative baseline and stimulated testosterone concentrations were consistent with castration. The testicular parenchyma of the testes that had been left in situ underwent coagulative necrosis. CLINICAL IMPLICATIONS: In ponies and juvenile stallions, normally descended testes can be removed laparoscopically. Nonpalpable inguinal testes can be left in situ after laparoscopically ligating and transecting the testicular artery and vein. Additional experience with these approaches is necessary before their use can be recommended in mature stallions.

Animals↗

PubMedDate not supplied

[Sexual behavior and alpha-2 adrenoreceptors in the neocortex of male rats after castration and testosterone administration].

Castration of male rats inhibited their sexual behaviour and increased the density of the alpha-2 adrenergic receptors in the brain cortex. Treatment of castrated or intact males with testosterone activated their sexual behaviour and decreased the receptor density in the brain cortex. The obtained evidence testify to the involvement of the brain alpha-2 adrenergic receptors in the effect of testosterone on male sexual behaviour.

Animals↗

PubMed1997

Effect of stanozolol on body composition, nitrogen balance, and food consumption in castrated dogs with chronic renal failure.

OBJECTIVE: To determine the effect of stanozolol on body composition, nitrogen balance, and food consumption in castrated dogs with chronic renal failure. DESIGN: Blinded crossover trial. ANIMALS: 22 castrated Beagles with experimentally induced chronic renal failure. PROCEDURE: Dogs were divided into 2 groups of 11 dogs each. During each of two 6-week treatment periods, dogs in 1 group received stanozolol, and those in the other group received a control agent. Nitrogen balance, body composition, and food consumption were determined. RESULTS: During administration of stanozolol, the amount of food consumed per dog, lean body mass, and nitrogen balance increased. Stanozolol did not have a significant effect on body fat, bone mineral content, or food consumption per kilogram of body weight. CLINICAL IMPLICATIONS: For dogs with mild-to-moderate, nonuremic, experimentally induced, chronic renal failure, stanozolol had positive effects on nitrogen balance and lean body mass.

Anabolic Agents↗

PubMed2026

Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study.

INTRODUCTION: Homologous Recombination Repair (HRR) genes alterations are a resistance mechanism to therapies by taxanes or Androgen Receptor Signalling inhibitors in Metastatic Castration Resistant Prostate Cancer (mCRPC). BRCA-mutated mCRPC patients are eligible to poly adenosine diphosphateribose polymerase inhibitors (PARPi). Therefore, assessing the population-specific prevalence of HRR-related genes alterations is of public healthcare importance. METHODS: This retrospective, non-interventional, multicentric study was conducted across 6 reference French centers in a "real-life" setting. 788 paraffin-embedded mCRPC patient-samples were included and submitted to testing for BRCA1/2 in six different centers; additionally, non-BRCA HRR-related genes were investigated in two different centers. RESULTS: Among the samples, n=602 (76.4%) were contributive for molecular testing. In multivariate analysis by logistic regression and sensitivity analysis, only sample age (P<0.01), sample surface area (P=0.02) and institution (P=0.018) remained statistically significant. BRCA alterations were detected in n=39/602 (6.5%) of contributive samples, with n=35 and n=4 alterations of BRCA2 and BRCA1 respectively. Non-BRCA HRR-related genes alterations were detected in n=12/157 (7.6%) of contributive samples, with alterations of mainly ATM (n=6, 3.8%), CDK12 (n=4, 2.5%) and CHEK2 (n=2, 1.3%). DISCUSSION: In this study, testing contributivity was similar or higher that of other studies in the literature, and observed mutations prevalences were similar to that of other screenings of western populations. Harmonising per-centres protocols and enhancing molecular testing contributivity with the screening of circulating DNA samples and expanding its range by including non-BRCA HRR-related genes in all reference centres will enable more patients to be accurately treated by targeted therapies. LEVEL OF EVIDENCE: 3 (grade C).

Male↗

PubMed2026

Expression patterns of potential targets for antibody-directed therapy in metastatic castration-resistant prostate cancer patients.

INTRODUCTION: Survival in metastatic castration-resistant prostate cancer (mCRPC) patients remains limited and treatment is complicated by tumor heterogeneity. As antibody-based therapeutics emerge, identifying actionable antigen targets and patient subgroups most likely to benefit is essential. MATERIALS & METHODS: Gene expression of 62 antibody-targetable proteins was analyzed in 296 mCRPC biopsies. These genes encode proteins targeted by approved or investigational antibody-based cancer therapeutics. Associations between target expression with genomic classifications and transcriptomic subtypes were evaluated. Target expression was also assessed in tumors with low expression of established mCRPC targets. Subgroup-specific targets were validated in an independent cohort and single-cell transcriptomics. RESULTS: Established targets KLK2, FOLH1 (PSMA) and STEAP1 showed the highest median expression across the cohort. Target expression did not correlate with genomic classifications, including homologous recombination deficiency, microsatellite instability, CDK12, TP53, PTEN or AR alterations Target expression did associate with transcriptomic subtypes: CRPC-AR (driven by androgen receptor-signaling) and CRPC-SCL (stem cell-like features, AP-1/YAP/TAZ-driven), displayed the highest expression of multiple targets, including KLK2, FOLH1, and SLC44A4. CRPC-NE (neuroendocrine phenotype) showed heterogeneous expression, with high CD46 expression, whereas CRPC-WNT (Wnt-signaling driven) generally showed low target expression. Notably, CD46 was highly expressed in tumors with low KLK2, FOLH1, and STEAP1 expression, a subgroup associated with poor prognosis. CONCLUSIONS: Although several antibody targets showed broad expression in mCRPC-tumors, expression varied by transcriptomic subtype. Subgroups such as CRPC-WNT expressed fewer targets, suggesting the need for alternative therapeutic strategies. CD46 emerged as a promising target, with wide expression across multiple subtypes, including clinically challenging CRPC-NE and mCRPC tumors lacking expression of established targets.

Humans↗

PubMed2026

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1 year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1 year occurred in 44% of the MDT group vs 75% in the OBS group (P = 0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4 months) compared to the OBS arm (2.9 months, P = 0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans↗

PubMed1996

Effect of aromatase inhibitor, TZA-2209, on the prostate of androstenedione-treated castrated dogs: changes in prostate volume and histopathological findings.

To determine whether the inhibition of estrogen-related effect in the prostate would be of value in the management of benign prostate hyperplasia (BPH), we examined the effect of TZA-2209, a new steroidal aromatase inhibitor, on the prostate in three of six castrated beagles that received 75 mg/week androstenedione. The three other animals served as controls. Sequential measurements of prostate volume by transrectal ultrasonography showed that the volume in TZA-treated dogs was significantly decreased compared with that in the controls. Prostatic aromatase activity was suppressed by TZA administration. Histopathologically, the stromal component was increased and glands were atrophied by androstenedione treatment. TZA administration increased the volume of the glands. Immunohistochemical detection of estramustine-binding protein showed more positive staining of the protein in the glands that were increased in volume by TZA administration. We concluded that the aromatase inhibitor effectively antagonized the estrogen-related stromal changes, however, this action was accompanied by stimulation of the glandular component due to the accumulation of androgens, the substrate of the aromatase. In the light of these findings, we suggest the simultaneous treatment for the androgen-glandular component route in the prostate is necessary for the effective management of BPH.

Androstenedione↗

PubMed1980

Pulmonary lymphangiomyomatosis: treatment with castration.

Pulmonary lymphangiomyomatosis (PLM) is a rare disease of smooth muscle proliferation that generally leads to an early death due to respiratory insufficiency. The disease only affects women. Exacerbations with pregnancy and after hormonal manipulation have been documented. There is presently no successful treatment of the disease. Castration as a means of early therapy has been associated with a stable respiratory picture in our patient. Peritoneal-jugular shunt can benefit women with significant ascities.

Castration↗

PubMed1982

Testosterone action on the ventral prostate lobe of the castrated rat as assessed with a stereologic morphometric method.

The effects of testosterone (1 mg testosterone propionate/100 g body weight for 30 days) on the ventral prostates of rats castrated 30 days prior to the onset of hormone treatment was investigated with a stereologic morphometric method. Testosterone induced rapid growth of the prostate, which was reflected by a 29-fold increase in acinar parenchyma but only a 2.6-fold increase in interacinar tissue. There was a 23-fold increase in the total amount of glandular epithelium and a 36-fold increase in total luminal amount. Various volumetric fractions, total surface area, total tubule length, height of the epithelium, mean diameter of the tubules, and mean distance between the tubules and between the glandular centers were calculated. Growth of the acinar parenchyma, especially of the glandular lumen, was the dominant pattern. We could not demonstrate any remarkable responses in the interacinar tissue during any phase of testosterone treatment.

Animals↗

PubMed1979

The differential absorptive activity of epithelial cells of the rat epididymus before and after castration.

Horseradish peroxidase introduced into the lumen of the rat epididymis was taken up by the columnar cells of the epithelium by five minutes and more so after longer periods. The apical cells and particularly the clear cells in the caput and cauda epididymis, respectively, showed significantly greater endocytotic activity than the principal cell in both locations. Within 14 days after castration, however, such differences in absorptive activity among the various cell types were essentially obscured because of increased endocytosis by the androgen-deficient principal cells. The results are discussed briefly in terms of the function of different epithelial cell types and secretory/absorptive activity in the epididymis.

Absorption↗

PubMed1983

Light and scanning electron microscopic study of testosterone-restored penile papillae in castrated rats.

Structural changes in various penile tissue from rats with differing circulating androgen levels were analyzed with light and scanning electron microscopy. Adult males were castrated and daily injected for 6 weeks with one of four physiologic amounts of testosterone propionate (TP). Results indicated that epithelium, subepithelial connective tissue, and the papillae protruding from the surface of the glans penis responded, more or less, in a dose-dependent fashion to the steroid. The least androgen-sensitive penile tissue was the epidermal stratum corneum, more sensitive was the maligiphian layer, and more sensitive still was the subepithelium. The penile papillae and their follicles were the most androgen-sensitive tissue. Specifically, the high testosterone, 400 micrograms and 800 micrograms TP, males experienced papillae that were thicker, taller, more densely arranged, and more highly keratinized than the lower testosterone, 100 micrograms and 200 micrograms TP, males. The function of the papillae may be to provide the female with the mechanical stimulation necessary to ensure a proper hormonal milieu for successful impregnation.

Animals↗