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PubMed1995

[Effects of castration on apoptosis and transforming growth factor-beta 1 mRNA in the neonatal mouse seminal vesicles].

BACKGROUND: In the adult male rat prostate, castration induces apoptosis of epithelial cells concomitant with the increase in transforming growth factor-beta 1 (TGF-beta 1). In the present study, we investigated the effects of castration on apoptosis and TGF-beta 1 mRNA in neonatal mouse seminal vesicles. METHODS: 5-day-old BALB/c mice were castrated by Pfeifer's method. We estimated the weight, 3H-thymidine uptake by whole seminal vesicles, the amount of TGF-beta 1 mRNA by RT-PCR method, and the apoptotic index of both epithelium and mesenchyme. RESULTS: The castration of 5-day-old neonatal mice resulted in much less weight of seminal vesicles and DNA synthesis estimated by 3H-thymidine uptake by whole seminal vesicles compared to intact neonatal mice, indicating that the growth of neonatal mouse seminal vesicles depends on androgens secreted by the testis. The amount of TGF-beta 1 mRNA estimated by RT-PCR method increased 4 days after castration at 5 days of age. However, the castration did not induce apoptosis in the seminal vesicles. CONCLUSION: The present study indicates that castration of neonatal mice does not induce apoptosis in the seminal vesicles, although it does a transient increase in TGF-beta 1 mRNA in the seminal vesicles.

Animals↗
PubMed1999

Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration.

Transforming growth factor (TGF)-beta1 is induced in the prostate after castration and has been implicated in apoptosis of epithelial cells during involution. TGF-beta1-mediated receptor activation induces phosphorylation of Smad2 and Smad3, which form complexes with Smad4, that translocate to the nucleus to regulate transcription of target genes. Smad6 and Smad7 antagonize the action of signal-transducing Smads. We have examined the immunohistochemical expression of different Smad molecules in the epithelium of rat ventral prostate before and after castration, in androgen-sensitive Dunning R3327 PAP prostatic tumor cells from untreated and castrated rats, and after treatment with estrogen. In the ventral prostate, a significant increase of phosphorylated Smad2 (P-Smad2) was observed after castration. In prostatic tumor cells we observed an increased expression of Smad2 and P-Smad2 after treatment. The levels of Smad3 and, in particular, Smad4 were enhanced in the normal ventral prostate, as well as in the tumors after castration. Interestingly, Smad6 and Smad7 expression was also up-regulated in cells with increased Smad2 activation. The staining for Smad2, P-Smad2, Smad3, Smad4, and Smad7 was nuclear in some cells and was present in areas with a large number of apoptotic cells identified by various morphological criteria, formation of apoptotic bodies and, in adjacent sections, by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Our results suggest that the signal transduction pathway for TGF-beta, leading to apoptosis, is activated in the normal prostate after castration and in the tumor model after castration, without or with estrogen treatment.

Animals↗
PubMed1999

Castration-induced apoptosis of androgen-dependent shionogi carcinoma is associated with increased expression of genes encoding insulin-like growth factor-binding proteins.

Insulin-like growth factor (IGF)-I has well-characterized mitogenic and antiapoptotic effects that are essential for maintenance of the normal prostate and may be important during regression of the normal prostate and/or prostate tumors induced by androgen-targeting therapies for prostate cancer. IGF-I activity is modulated by IGF-binding proteins (IGFBPs). Here we examine IGFBP expression during regression of androgen-dependent Shionogi carcinoma tumors after castration. In this model, we observe a 90% reduction in Shionogi tumors by 10 days postcastration. Northern blotting of RNA from tumors collected at various times after castration indicates a rapid induction of IGFBP-5 concomitant with apoptotic regression of tumors, as detected by Apoptag staining of tumor sections after castration. IGFBP-5 mRNA was not detectable in tumors from control animals, but levels increased 120-fold in tumors 3 days after castration. The mRNAs for IGFBP-3 and 4 were abundant in Shionogi tumors from intact mice and decreased to -33% and -20% of control, respectively. Castration had no significant effect on IGFBP-2 expression. Treatment with calcium channel blockers inhibited castration-induced apoptosis and tumor regression and also significantly inhibited up-regulation of IGFBP-5 after castration. These data provide strong evidence for a functional role of IGFBP-5 expression in mediating the apoptosis induced by androgen deprivation in androgen-dependent neoplasia.

Amlodipine↗
PubMed2000

Altered synaptic transmission in the hippocampus of the castrated male mouse is reversed by testosterone replacement.

PURPOSE: To determine the effect of castration on hippocampal function, we have investigated synaptic transmission in the castrated male mouse in vivo. We also examined whether administering testosterone can reverse the changes. MATERIALS AND METHODS: Male 12 weeks-old C57BL/6J mice were divided into three experimental groups; sham-castration (Control), the castration group (Cast), and the castration plus testosterone propionate group (Cast+TP). Field excitatory postsynaptic potentials (fEPSP) were evoked in the CA1 area of the hippocampus by stimulating the commissural fibers of the contralateral hippocampus. Field EPSPs were evoked in the granular cells of the dentate gyrus (DG) by stimulating the ipsilateral perforant path fibers. RESULTS: Laminar analysis of the fEPSPs in the hippocampal CA1 pyramidal cell layer did not differ significantly between the three experimental groups. However, paired pulse facilitation (PPF) of the fEPSP with short inter-stimulus intervals (30 to 100 msec) was significantly suppressed in Cast group. This suppression was reversed by testosterone injection (Cast+TP). Longterm potentiation (LTP) in the CA1 pyramidal neurons by high frequency stimulation (HFS) did not differ significantly between the three experimental groups, whereas potentiation evoked by primed burst stimulation (PBS) was much weaker in the Cast group compared with the Control group. Testosterone injection restored the PBS-induced potentiation to the control level. Synaptic transmission between perforant pathway and the granule cells in the dentate gyrus (DG) did not differ significantly among the three experimental groups. CONCLUSIONS: Suppression of PPF and impairment of the potentiation by PBS in CA1 hippocampal neurons was observed in castrated male mice and these changes were reversed by testosterone injection. These findings suggest that altered synaptic transmission in the castrated male mouse is caused by disturbance of inhibitory neuronal networks that are influenced by testosterone.

Animals↗
PubMedDate not supplied

Castration induces apoptosis in the male accessory sex organs of Fas-deficient lpr and Fas ligand-deficient gld mutant mice.

The role of the Fas ligand-Fas system in castration-induced apoptosis in the epithelia of the ventral prostate (VP), seminal vesicle (SV), coagulating gland (CG) and epididymis (Ep) was investigated using lpr/lpr, and gld/gld mutant mice which are deficient in Fas and Fas ligand, respectively. The degree of apoptosis in the epithelium was quantitatively estimated by an apoptotic index (a percentage of apoptotic cells). The weights (mg/10 g body weight) of the VP, SV, CG and Ep of lpr/lpr and gld/gld mice were similar to those of normal +/+ mice and castration decreased the weights of the VP, SV, CG and Ep in these three kinds of mice to similar levels. Castration also increased the apoptotic indices in these organs reaching maximum on days 2-6 after castration. There was no significant difference in the apoptotic index of these organs among +/+, lpr/lpr and gld/gld mice on days 0-8 after castration. Agarose gel electrophoresis of DNAs extracted from the VP, SV, CG and Ep of +/+, lpr/lpr and gld/gld mice on day 4 after castration showed a ladder pattern. The present results suggest that the Fas ligand-Fas system plays little role in castration-induced apoptosis in the mouse male accessory sex organs such as the VP, SV, CG and Ep.

Animals↗
PubMed2005

Costs and complications of equine castration: a UK practice-based study comparing 'standing nonsutured' and 'recumbent sutured' techniques.

REASONS FOR PERFORMING STUDY: Clinicians are often asked to guide owners and trainers over the relative advantages and disadvantages of equine castration performed in either the standing horse with an open unsutured scrotal wound with healing by second intention, or a recumbent horse under general anaesthesia in aseptic conditions, with sutured scrotal skin allowing primary wound closure. OBJECTIVES: To identify types and frequency of complications following the 2 differing approaches, and to compare the financial cost associated with each procedure, based on practice charges. METHODS: Veterinary expenses of 217 horses castrated by a Newmarket equine veterinary practice over an 18-month period were analysed. Of these, Group 1 (n = 121) were castrated standing and nonsutured by one of 2 ambulatory clinicians and Group 2 (n = 96) castrated in recumbency, in aseptic equine hospital conditions. RESULTS: Group 1 had a complication prevalence of 22% with no mortalities, and Group 2 a significantly lower complication prevalence of 6% (P = 0.001) with a mortality rate of 1%. The financial cost of Group 1, without complications, was approximately one-third of the cost of uncomplicated Group 2. However, the cost of Group 1 with complications increased to approximately two-thirds of the cost of an uncomplicated Group 2 castration. CONCLUSIONS: Even though the complication prevalence for Group 1 castrations leaving an open scrotal wound was significantly higher than for a recumbent horse with a sutured scrotal wound in a hospital, the average cost of Group 1 was still less, even taking into account the additional follow-up costs associated with treating such complications. POTENTIAL RELEVANCE: This report provides a benchmark for the outcome of 2 methods of castration based on a database obtained from particular circumstances within the practice involved. Further studies are required to corroborate and take into account future development in surgical and anaesthetic techniques.

Animals↗
PubMed2006

[Castration affects the expression of androgen receptor and epidermal growth factor in rat submaxillary salivary gland].

OBJECTIVE: To investigate the effect of castration on the quantity of androgen receptor (AR) and the epidermal growth factor (EGF) in the submaxillary salivary glands of castrated rats. METHODS: Sixty male Wistar rats, aged 30 to approximately 60 days, were randomly divided into three groups of 20 rats: castrated, sham-operated and normal control (unoperated). The submaxillary salivary glands of the castrated rats were removed one week after surgery, and so were those of the rats in the sham-operated and the normal control groups. The homogenized salivary gland was used for Western-blots. RESULTS: The quantity of AR and EGF in the submaxillary salivary glands was decreased significantly in the castrated rats compared with that in the sham-operated and the normal control ( P < 0. 05). Moreover, EGF secreted by the submaxillary salivary glands was also decreased in the castrated rats (P < 0.05). CONCLUSION: Castration affected the production of androgen receptor in the salivary gland, and also, could further affect the secretion of EGF from the salivary gland.

Animals↗
PubMed1990

The effect of neonatal castration of male rats on the level of sex-hormone receptors in the hypothalamus and hypophysis of adult animals.

The concentration of oestradiol (E2) and testosterone (T) cytosolic and nuclear receptors was studied in the pituitary and hypothalamus of adult male rats gonadectomized either on the first day after birth (long-term castrates) or in adulthood (short-term castrates). Intact male rats and short-term castrates had the same levels as each other of cytosolic and nuclear oestrogen and androgen receptors in the pituitary, mediobasal hypothalamus (MBH), and preoptic anterior hypothalamus (POAH). In neonatally castrated males the number of nuclear T-binding sites in the pituitary and both areas of the hypothalamus decreased, whereas the number of nuclear E2-receptors was reduced only in the MBH. The number of E2-receptors in the POAH of such animals increased. The number of E2- and T-binding sites in the nuclear fraction of the MBH and POAH was the same in long-term castrates whether they did not receive testosterone propionate (TP) or received it from 7 days after birth until sexual maturity. Conversely, the T-receptor concentration in the hypophysis of neonatally castrated males who received TP was higher than in such animals which did not, but still lower than the level in intact adult rats; the number of hypophyseal nuclear E2-binding sites in long-term castrates which received TP was 1.5 times higher than in all the other groups of animals. The data demonstrate that in male rats sex-hormone receptors are involved in the sexual differentiation of the brain.

Animals↗
PubMed1989

Inhibition of a transplantable pancreatic carcinoma by castration and estradiol administration in rats.

Influence of sex steroids on the growth of an azaserine-induced transplantable rat pancreatic carcinoma, DSL-2, was studied. This established transplantable tumor has been maintained in syngeneic rats. Inbred male Lewis rats were pretreated with castration and s.c. implantation of 1.0-mg 17 beta-estradiol (CAS: 50-28-2; estradiol) pellets at 7 weeks of age. Tumor cells were inoculated s.c. on the back of intact male, castrated male, or 17 beta-estradiol-treated castrated male rats. Additional male rats served as non-tumor-bearing controls. There was no difference in the body weight between tumor-bearing and non-tumor-bearing male rats. A distinct difference in the tumor growth was observed in variously conditioned recipients. In castrated male hosts, the serum testosterone levels and the epididymis weights were significantly decreased, and the tumor weights were significantly less as compared to intact control hosts. Additional pretreatment with 17 beta-estradiol caused a markedly slower growth of tumors and increases of the serum 17 beta-estradiol levels and the pituitary weights in castrated male recipients. The remarkable response of tumor growth to castration was also observed in a fast-growing tumor derived from DSL-2. Moreover, close positive relationships between tumor weights and the activities of both serum amylase and lipase were observed. Results showed that the pretreatment with castration alone or in combination with 17 beta-estradiol treatment was able to inhibit the growth of the transplantable tumor. In addition, tumor cells had an ability to produce amylase and lipase, and the amount of enzymic activity was related to the tumor volume. Thus, these data indicate that the transplantable rat pancreatic carcinoma retains physiological function. Our previous study has shown the modulation by sex steroids of azaserine-induced preneoplastic lesions of pancreas in rats. Therefore, androgens and estrogens may play key roles as promoters and inhibitors during the process of pancreatic carcinogenesis.

Amylases↗
PubMed1993

Redox capacity of the pineal gland in rats. Effect of castration.

The day/night cycle-induced effects, and the effect of castration on pineal oxidative potential in rats, were studied herein. Experiments were made in adult and castrated Wistar rats kept under normal light conditions during winter (on December and January). Castration was performed 72 hrs before sacrification. Groups of 6 intact or castrated animals were sacrificed at 4 hr-intervals during 24 hrs (the day/night cycle). Blood and pineal were then taken. Peroxides and total pineal antioxidants in plasma and pineal homogenate were assessed by chemiluminescence. The results obtained prove that photoperiod is involved in the organism oxidative potential, and that pineal is involved in the diurnal rhythm of this potential. Pineal peroxide and antioxidative concentrations show circadian variations with minimum and maximal values during the day or the night, which are also reflected at the plasma level. In the first half of the morning are registered increased peroxide and decreased antioxidative levels while at night the diagrams are reversed. As compared to the intact group, in the castrated one antioxidants and peroxides maintain their biorhythms but their concentrations are significantly changed. The diagram of pineal peroxides in the castrated group is situated above that of the intact one, with statistically significant differences only at midday (12:00). Taking into account the antioxidative characteristics of melatonin, one can suppose that maximum pineal antioxidative levels during the night might be due to maximum concentrations of nocturnal melatonin. The significant increase in peroxide concentration and the decrease in antioxidants after castration would partly explain the physiologic status of the elderly with decreased melatonin production and increased oxidative processes.

Animals↗
PubMed1994

Relationships between local circulatory changes in the tibia and kidney of male and female rats after castration and administration of estradiol or testosterone.

The effects of castration and of the four weeks' administration of estradiol or testosterone on the blood circulation in the tibia and the kidney (expressed as the 85Sr-microsphere uptake values, which are not influenced by simultaneous changes in cardiac output) were studied in four experiments on a total of 147 rats (68 females, 79 males), relative weights being noted at the same time. 85Sr-microsphere uptake in the tibia rose markedly after castration in both males and females, fell after estradiol benzoate in intact females and intact and orchidectomized males and also fell after testosterone in intact and oophorectomized females and orchidectomized males. 85Sr-microsphere uptake in the kidney rose after castration only in males in experiments B; it fell after estradiol in orchidectomized males and fell after testosterone in intact females and males and in orchidectomized males. Relative tibial weight fell in castrated females, but in castrated males only in experiment D; after estradiol it rose only in males (intact and orchidectomized) and rose after testosterone in intact and oophorectomized females and orchidectomized males. Relative kidney weight fell after castration in both males and females, rose after estradiol in intact females and intact and orchidectomized males and rose after testosterone in intact and castrated males and females. In all four experiments there was a demonstrable statistically significant correlation between the 85Sr-microsphere uptake values in the tibia and the kidney. The relative weights displayed a similar correlation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Endometriosis persisting after castration: clinical characteristics and results of surgical management.

OBJECTIVE: To identify the clinical characteristics and response to surgical treatment of endometriosis-associated pain in castrated women. METHODS: In a prospective, longitudinal observational study, 75 patients with previous castration had biopsy-proven endometriosis excised surgically. Anatomical characteristics of disease were studied using pelvic mapping and compared to the findings in non-castrated women with endometriosis. Preoperative and postoperative verbal analogue pain scales were used to gauge the response to excision of endometriosis. RESULTS: Patients treated surgically for endometriosis following castration were significantly older (37.8 +/- 8.1 versus 31.3 +/- 6.9 years, mean +/- standard deviation; 95% confidence interval [CI] 4.9-8.1) and slightly more likely to have intestinal involvement (risk ratio 1.3, 95% CI 0.94-1.8) than non-castrated endometriosis patients. Most had marked alleviation of pain after excision of endometriosis. CONCLUSIONS: Endometriosis can remain symptomatic after castration, with or without estrogen therapy. In such patients, there is a 33% frequency of intestinal involvement. At castration, consideration should be given to removal of invasive peritoneal and intestinal disease. Symptom improvement occurs in most patients after excision of endometriosis.

Adult↗
PubMed1997

Expression of glutathione-peroxidase (GSH-PO) in the rat ventral prostate--effect of castration and administration of testosterone.

Immunolocalization of glutathione-peroxidase (GSH-PO), apoptosis and bcl-2 protein in the rat ventral prostate was investigated in the presence or absence of androgen. Male Sprague-Dawley rats were divided into four experimental groups. Group 1 consisted of intact controls. In group 2, rats were sacrificed two days after castration. In groups 3 and 4, rats were administered subcutaneously 1 mg/animal of testosterone-propionate daily for three or seven days at two days after castration. The intensity of GSH-PO staining in the glandular epithelial cells of the ventral prostate was remarkably decreased after castration (Group 2), and it clearly recovered when testosterone was administered (Groups 3 and 4) to the castrated rats. The prostatic GSH-PO mRNA levels were diminished in the castrated rat ventral prostate but greatly increased by testosterone (Groups 3 and 4). Furthermore, castration (Group 2) induced apoptosis in the prostatic glandular epithelial calls and the apoptosis was reduced by testosterone-administration (Groups 3 and 4) to the castrated rats. In groups 3 and 4, expression of bcl-2 protein was clearly detected in the glandular epithelial cells of the ventral prostate. These findings strongly suggested that expression of GSH-PO and bcl-2 protein in the glandular epithelial cells of the rat ventral prostate is testosterone-dependent.

Animals↗
PubMed1984

The relationship of epithelial cell types in the ventral prostate glands of castrated mice treated with testosterone.

The purpose of this study was to determine the relationship of epithelial cell types in the ventral prostate glands of castrated mice treated with testosterone during the period of maximum DNA synthesis, mitosis, and restitution of the epithelium. Of 33 adult mice, ten were used as normal controls, six were used as castrated controls at day zero of treatment, and 17 castrates were treated with testosterone for 1 through 8 days. Selected normals, castrates, and treated mice were injected with 3H-thymidine prior to their sacrifice. Tissue samples from each mouse were processed for electron microscopy and autoradiography. The epithelium of the ventral prostate glands after testosterone treatment had four cell types: basal, intermediate, mitotic, and columnar. Intermediate and mitotic cells were most frequent during the second, third, and fourth day of androgen treatments. Basal and columnar cells were observed in normal, castrates, and androgen-treated mice. The restitution of the epithelium included an initial phase of cell growth which was essentially complete by the fifth day of hormone treatment. During the growth phase many basal and columnar cells synthesized DNA and became mitotic. Columnar cells increased their cell height and showed variable amounts of organelles and inclusions. The growth phase was followed by the secretory phase in which columnar cells contained abundant supranuclear organelles and inclusions and appeared as secretory cells much as those observed in normal prostate. The restitution process of the prostate glands of castrates was completed by the eighth day of hormone treatment.

Animals↗
PubMed1982

Sexual imprinting in male Japanese quail: the effects of castration at hatching.

This study investigated whether gonadal hormones are required for sexual imprinting in male Japanese quail during the period of exposure to the imprinting stimulus. Brown males were either castrated or laparotomized on the day of hatching. Between Days 10 and 30 of age castrated males (N = 15) and intact laparotomized males (N = 10) were exposed individually to white females. A 2nd group of intact laparotomized males (N = 13) were exposed to brown females. When adult (Day 54), 7 of the castrated males were treated with testosterone propionate (TP): the remaining 8 castrated males and intact groups received saline. All males were given choices between novel white and novel brown females starting on Day 62. The TP-treated castrated males behaved like intact white-exposed males, preferring to approach and copulate with white females significantly more readily than did intact brown-exposed males. The untreated castrated males showed no sexual behavior. The results indicate that gonadal hormones are not required during the period of exposure to an imprinting stimulus in male Japanese quail.

Animals↗
PubMed2005

Castration triggers growth of previously static androgen-independent lesions in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

BACKGROUND: Androgen-deprivation remains the standard of care for metastatic prostate cancer, yet its total impact on the course of disease is incompletely established. METHODS: We have examined the long-term effects of castration upon the progression of established cancer in the TRAMP transgenic mouse model of prostate cancer. Mice castrated at 15-weeks of age, as well as intact littermates, were followed until spontaneous death from cancer. RESULTS: Statistical analyses of age-at-death versus primary tumor mass revealed that mice segregate into two categories of response to androgen-deprivation. In Category One, the act of castration paradoxically triggers the growth of microscopic androgen-independent lesions, as evidenced by a statistical synchronization of primary tumor growth. Delaying castration until 20-weeks of age delays the synchronized growth of these tumors, as well as the deaths of the host mice. In Category Two, castration eliminates or substantially delays primary tumor growth, but fails to eliminate metastases. so that castration is found to impart no long-term survival advantage. CONCLUSIONS: We propose a two-step model for the alteration of androgen signaling in prostate cancer capable of explaining the above paradoxical results, which is based upon the dualistic role of androgens as both survival and differentiation factors. This model makes specific predictions for clinical intervention that are discussed in light of published studies.

Androgens↗
PubMed1996

Effects of 8-OH-DPAT on sexual behavior of male rats castrated at different ages.

The effects of the 5-hydroxytryptamine (5-HT) 1A receptor agonist, 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), on the sexual behavior of male rats castrated at adulthood or during the early postnatal critical period for brain differentiation are presented. In adult castrated males, two distinct groups of animals, divided according to their copulatory activity impairment following castration, were identified: animals that reached a low intromission frequency around Day 60 after testes removal (early reduction group) and males that retained the behavior until approximately Postcastration Day 180 (late reduction group). 8-OH-DPAT (0.10 mg/kg) increased intromission frequency in both groups, but the effect was more pronounced in rats that had a late reduction of mating behavior after castration. In males castrated at 6 hr or 12 days after birth, an increase in intromission frequency, but not in ejaculatory behavior, was also detected following the injection of 8-OH-DPAT (0.10 or 0.25 mg/kg) at adulthood. In conclusion, 8-OH-DPAT was able to enhance intromission behavior, bypassing the lack of testosterone either at the neonatal critical period or at adult age. The 5-HT1A system would exert a parallel modulatory action, in addition to testosterone, on male sexual behavior. Alternatively, since neonatal castrated males showed no ejaculatory behavior after 8-OH-DPAT injection, 5-HT and testosterone would act in an interactive way for the full expression of copulatory behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1980

Effects of castration on the bone structure of male rats: a model of osteoporosis.

Forty young (23-day-old) and thirty old (1-year-old) male rats were castrated and sacrificed with controls at intervals up to 18 months of age. No differences were observed between femurs or mandibles of rats castrated at 23 days and those of controls. Year-old castrate rats developed femoral osteoporosis after 2 months, which became more pronounced 4 months after castration. This was characterized by reductions in femoral density, dry weight, dry weight per unit length, and ash weight, and by the appearance of resorption cavities in diaphyseal walls and a sparsity of trabeculae in metaphyses and epiphyses of castrate femurs. These results indicate that the year-old castrate male rat may be a valuable experimental model for studies of the treatment of osteoporosis.

Animals↗