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PubMed2004

Effect of nonsteroidal antiandrogen monotherapy versus castration therapy on neuroendocrine differentiation in prostate carcinoma.

OBJECTIVES: To determine whether the administration of the nonsteroidal antiandrogen bicalutamide reduces the risk of an increase in chromogranin A (CgA) levels in patients with prostate cancer who experienced biochemical failure after radical retropubic prostatectomy (RRP) compared with pharmacologic castration therapy. It has been hypothesized that continuous androgen suppression for the treatment of prostate cancer results in hyperactivation of neuroendocrine cells and an increase in CgA levels. METHODS: Forty-eight patients with pT3pN0M0 prostate cancer and biochemical (prostate-specific antigen) progression after RRP were randomized to bicalutamide monotherapy or pharmacologic castration. The serum levels of CgA and prostate-specific antigen were measured at 1, 3, 6, 12, 18, and 24 months of therapy. The changes in serum CgA levels were compared for patients who successfully responded to the first 24 months of therapy. RESULTS: In both treatment groups, a statistically significant trend was noted for CgA levels to increase from baseline to 24 months. This trend was lower in the bicalutamide group (slope = 0.60, 95% confidence interval 0.28 to 0.92; P = 0.004) than in the castration group (slope = 0.29, 95% confidence interval 0.08 to 0.50; P = 0.01). CONCLUSIONS: The results of this study provide the first evidence to show that in patients with prostate cancer undergoing hormonal therapy, nonsteroidal antiandrogen monotherapy produces a significantly lower increase in serum CgA compared with castration.

Adenocarcinoma↗
PubMed1998

Comparative effects of neonatal and prepubertal castration on craniofacial growth in rats.

The role of endogenous testosterone in the craniofacial growth of the young male rat was investigated. First, the effect of neonatal surgical castration was examined in a randomized, cross-sectional study in which male Wistar rats were allocated to be either castrated or sham-operated 4 h after birth. Then, the effect of prepubertal chemical castration was analysed in a second, randomized longitudinal study in which male Wistar rats were randomly allocated either to a control group or to two experimental groups, one injected with triptorelin at day 25 and the other injected on day 25 and on day 45. Every tenth day between 20 and 70 days of age for the first study, and between 30 and 110 days of age for the second, body length and weight were measured, cephalometric X-rays taken, and blood samples obtained. Neonatal and prepubertal castration resulted in decreased plasma concentrations of testosterone and in delayed growth of somatic and craniofacial components. The initiation, duration and magnitude of the effect was dependent on individual bones (cranial base, skull roof) and on the lower incisor, and related to the testosterone concentrations. These results suggest that testosterone effects participate in the process of normal craniofacial growth, particularly during puberty.

Aging↗
PubMed2002

Long-term castration effects motoneuron size but not number in the spinal nucleus of the bulbocavernosus in the adult male Mongolian gerbil.

The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic group of motoneurons in Rexed's Lamina X of the lumbosacral spinal cord of the Mongolian gerbil. The SNB innervates the perineal musculature, the bulbocavernosus (BC), levator ani (LA), and external anal sphincter (EAS). Recent studies demonstrated a peripubertal component to the masculinization of the gerbil SNB with an apparent increase in both motoneuron size and number after puberty as measured with a Nissl stain. However, these studies could not determine if the apparent change in motoneuron number were due to the long-term castration involved in the methodology or due to a loss of motoneuron size beyond the point of being recognizable as motoneurons. Therefore, the current study was undertaken to examine this possibility by repeating the experimental protocol from previous peripubertal studies, on adult male gerbils with the addition of retrograde tract-tracing. Adult male gerbils were castrated at postnatal day (PND) 150 and given subcutaneous implants of testosterone proprionate (TP), dihydrotestosterone (DHT), estradiol benzoate (EB), EB and DHT, no steroid, or left intact. At PND215, the animals were injected with fluorogold (FG), a retrograde tract-tracer. At PND220, the animals were aldehyde perfused transcardially. The spinal cords were sectioned and alternate sections processed for either thionin-stain or FG visualization. Results indicated that long-term castration had no effect on SNB motoneuron number but did decrease SNB motoneuron size. TP, and to a lesser extent DHT, treatment could prevent the reduction in motoneuron size, however, EB could not. This study indicates that the maintenance of the adult male gerbil SNB-BC system is androgen, not estrogen, dependent and that long-term castration does not reduce motoneuron size to the point where they can no longer be distinguished.

Animals↗
PubMed1998

Parasitic castration of Pseudaletia separata by Cotesia kariyai and its association with polydnavirus gene expression.

Parasitization by the endoparasitoid Cotesia kariyai caused the inhibition of spermatogenesis of Pseudaletia separata. This phenomenon is called parasitic castration. The degree of castration was dependent on the host stage parasitized. Host parasitized on day 1 of the 4th stadium (the time of primary spermatocyte accumulation), had testicular cells with abnormal chromosomes appearing two days after parasitization, and spermiogenesis was completely inhibited. However, when hosts were parasitized on day 0 of the 6th (final) stadium, the degree of castration was less severe, and elongated cells appeared similar to those found in nonparasitized larvae. Results of this study involving injection of C. kariyai polydnavirus (CkPV) and venom suggested that these wasp components caused the appearance of abnormal chromosomes in specific germ cells, which were in mitotic or meiotic prophases. The amount of CkPV gene expression in host testes increased immediately after parasitization and reached a maximum 12h later. The early-expressed CkPV gene(s) may be related to the parasitic castration phenomenon.

Journal Article↗
PubMed1990

Proteins of the rat prostate. III. Effect of testosterone on protein synthesis by the ventral prostate of castrated rats.

Protein synthetic activities in the ventral prostate were assessed by two-dimensional electrophoresis in either four-day or seven-day castrated rats at different intervals following subcutaneous implantation of testosterone-filled silastic tubings for a period of up to four days. Prostatic tissues were cut into one to two mm. pieces and incubated in tissue culture medium containing S35-methionine (100 microCi/ml.) at 37C under 95% oxygen and 5% carbon dioxide for four hours. The incubated tissues were subjected to two-dimensional electrophoresis and radiofluorography. Analysis of protein spots detected in the fluorograms by computer-assisted densitometry revealed temporal changes in the synthesis of individual proteins by the ventral prostate of castrated rats following androgen treatment. Changes in two groups of proteins were evaluated: castration-induced proteins and androgen-dependent proteins. The level of synthesis of three castration-induced proteins (spots G, H, and I) declined rapidly upon testosterone treatment and reached a non-detectable level for spots G and H and a low level of synthesis for spot I by three days following androgen treatment. Synthesis of androgen-dependent proteins (spots D, E, and F) was activated by testosterone treatment. However, the time interval required to activate the synthesis of these proteins is different. Synthesis of protein spot D (prostatic binding protein) was detected as soon as half hour after the treatment. Synthesis of spots E and F, on the other hand, was not activated until 24 and 48 hours after the treatment, respectively. These changes in patterns of protein synthesis represent the characteristics of cellular responses to testosterone stimulation by the regressed prostate.

Animals↗
PubMed1998

Effects of castration on the lymphocytes of the thymus, spleen and lymph nodes.

It is well known that the thymus plays an important role in the development and maintenance of a competent immune system. The thymus atrophies with age, a process that is accelerated after puberty when there is elevation of serum sex steroid levels. We have used a panel of commercial monoclonal antibodies against various T and B cell surface markers to investigate the post-castration histological alterations in the thymus, spleen and lymph nodes of male Sprague-Dawley rats. Castration of 5-week-old male rats produced a significant increase in thymic weight (P < 0.05) compared to age-matched intact animals. The major observations from the immunohistochemical studies were post-castration elevations in staining for total T cells (MRC OX 19 and W 3/13), CD8 cells (MRC OX 8), B cells (MRC OX 12 and MARK-1) and cells bearing activation markers such as IL-2 receptor (MRC OX 39), transferrin receptor (MRC OX 26) and major histocompatibility class II antigen (MRC OX 6). These data suggest that following castration there is an increase in the ability of lymphocytes to respond to activation. As a result, there are elevated numbers of immature thymocytes within the thymus that undergo differentiation/maturation and consequently produce an increase in peripheral T and B cells.

Animals↗
PubMed1999

Early castration reduces prostatic carcinogenesis in transgenic mice.

OBJECTIVES: To test the hypothesis that transgenic mouse models of prostate cancer could be useful for testing chemoprevention strategies by evaluating the effects of early castration on prostate carcinogenesis in TRAMP mice. Human prostate cancer, unlike other cancers, requires androgens for oncogenesis yet acquires partial androgen independence in the castrated milieu. This paradigm is the basis for an ongoing clinical trial using selective androgen deprivation for prostate cancer chemoprevention. However, preclinical correlates for hormonal prevention or other chemoprevention strategies of prostate cancer have not previously been demonstrated in autochthonous models of prostate carcinogenesis. METHODS: Magnetic resonance imaging was used to longitudinally measure prostate growth in castrated and noncastrated TRAMP mice, and mice were prospectively examined for the onset of advanced, palpable prostate cancer. Modulation of androgen-responsive oncogene expression, as well as oncogene expression in refractory cancers, was evaluated by Western blot. RESULTS: Early castration significantly reduced prostate tumor growth as measured by magnetic resonance imaging and improved cancer-free survival. Prevention of prostate cancer development in these mice was associated with durable suppression of androgen-responsive oncogene expression (T-antigen expression not detectable by Western blot); prostate cancers refractory to the hormonal prevention strategy demonstrated androgen-independent oncogene expression. CONCLUSIONS: These findings suggest that carcinogenesis related to androgen-responsive oncogene expression can be prevented in some cases by hormonal manipulation and that transgenic TRAMP mice are useful for the preclinical evaluation of hormonal and possibly other strategies of prostate cancer chemoprevention.

Age Factors↗
PubMed1999

Involvement of the spinal serotonergic system in analgesia produced by castration.

The involvement of spinal serotonergic system in testosterone influence on formalin-induced pain was studied in male rats. Four weeks after castration, there was an analgesia in the late phase of formalin test that was reversed by intraperitoneal injection of testosterone enanthate (1 mg/kg) for 3 days. Flutamide (testosterone antagonist) produce analgesia in the late phase on intraperitoneal (10 mg/kg, IP) and intrathecal (60 microg/rat, IT) injections, but not on intracerebroventricular (60 microg/rat, ICV) administration. The antinociceptive effect of castration and IP flutamide (10 mg/kg) was abolished by pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 100 microg/rat, IT). IT-administered 5-HT (100 microg/rat) produced analgesia in the early and late phase of formalin test. Microdialysis sampling was used to characterize the extracellular concentration of 5-hydroxytryptamine (5-HT, serotonin) in the dorsal horn of the lumbar spinal cord. This technique demonstrated that levels of 5-HT were increased in 4-week castrated and IP flutamide (10 mg/kg) injected rats. The results may indicate that the analgesia produced by castration and flutamide administration is mediated through functional alteration in spinal cord serotonergic system.

5,7-Dihydroxytryptamine↗
PubMedDate not supplied

Changes in the development of experimental autoimmune prostatitis (EAP) by castration in aged rats.

During Experimental Autoimmune Prostatitis (EAP), 12-month-old rats show a higher cellular autoimmune response and lower humoral autoimmune response against prostatic components than 3-month-old rats subjected to the same antigen stimulus. We analyzed if thymus recovery by orchidectomy could affect the development of EAP in 12-month-old rats. Thirty days after gonadectomy, 12-month-old rats showed an increment in the thymic mass and in the thymocytes absolute number, with percentages of the four main cell subpopulations (defined by CD4-CD8 molecules expression) similar to the 3-month-old rats. The DTH response of castrated 12-month-old with EAP were diminished in comparison with sham-castrated 12-month-old rats with EAP, resembling the values observed in 3-month-old rats with EAP. The prostates of castrated 12-month-old rats with EAP did not show inflammatory mononuclear cell infiltration, as did control 3- and 12-month-old rats with EAP. Castration seems to modulate negatively EAP in 12-month-old rats, possibly through the regeneration of thymus after testosterone deprivation.

Aging↗
PubMed1987

Rapid eye movement sleep deprivation affects sleep similarly in castrated and noncastrated rats.

Twenty-four-hour recordings of electrophysiological correlates of the sleep-waking cycle in castrated and noncastrated Wistar rats were performed to validate the cuff pedestal technique in the deprivation of rapid eye movement sleep. An undisturbed pattern of sleep was found in both castrated and noncastrated rats when the cuffs were in the raised position. The lowering of the cuff for 4 days virtually abolished REMs in both groups of rats. During neither the dark nor the light period was there any difference between the castrated and noncastrated rats in the total amount of REMs rebound. The results accord with the data obtained by the conventional flowerpot procedure and show that castration does not influence the amount of REMs before, during, and after REMs deprivation in the rat. It is suggested that testicular testosterone, contrary to growth hormone, is not essential for the triggering of REMs sleep, although both have anabolic actions.

Analysis of Variance↗
PubMed1991

Effects of testosterone on the liver of castrated rats: morphologic study.

It is well known that castration in rats causes atrophy of the sexual organs and, to a lesser extent, of other organs. We have observed that castration causes a reduction of the liver weight due to a reduction (-10%) of the numerical density of the hepatocytes after castration (p less than 0.01). Testosterone administration at high concentration (2.5 mg/100 g b. wt.) as well as at low concentration (0.025 mg/100 g) in the castrated rats causes an increase of the liver weight due to an increase (+30%) in the cellular area (p less than 0.001) as well as in the nuclear area (+20%) (p less than 0.01) of the hepatocytes, revealing a powerful hypertrophic effect of the hormone in the liver.

Animals↗
PubMed2002

Castration increases nisoxetine-evoked norepinephrine levels in vivo within the olfactory bulb of male rats.

In the present experiment we compared differences in extracellular norepinephrine levels in vivo within the olfactory bulb of intact and castrated male rats following infusion of the norepinephrine transport inhibitors, nisoxetine and tomoxetine. With this approach it was possible to assess whether dynamic changes in in vivo norepinephrine transporter function occur as a function of the gonadal state of the animal. Norepinephrine levels following infusion of nisoxetine were significantly increased in castrated compared with intact male rats. While a similar trend was present in response to tomoxetine infusion, these differences failed to achieve a statistically significant difference. These results demonstrate that castration of male rats alters norepinephrine transporter function within the olfactory bulbs. The increased extracellular levels of norepinephrine in response to agents which inhibit transporter function suggest that castration reduces transporter activity. Such effects have important implications not only with regard to processes involving the norepinephrine system in the olfactory bulb but also to the generalized sites and mechanisms by which gonadal steroid hormones modulate central nervous system functions.

Animals↗
PubMed1998

Gamma-aminobutyric acid-immunoreactive neurons in the amygdala of the rat - sex differences and effect of early postnatal castration.

The distribution of GABA-immunoreactive neurons in the rat amygdala was determined by immunohistochemical methods. Sex differences in the number of GABA-immunoreactive cell bodies were observed in the medial, central, cortical and basolateral amygdaloid nuclei. Females had more numerous GABA-expressing neurons than males (P < 0.01). Castration of neonatal males had controversial effects on this sex difference in the different parts of the amygdaloid complex. In the cortical and basolateral amygdala castrated males showed a female pattern of GABA-expression. In the central amygdala no effect of castration on the number of GABA-immunoreactive cells was found. In the medial amygdaloid nucleus numbers of GABAergic neurons in castrated males differed both from intact males and females. The results of the present study suggest that the expression of GABA in the neurons of the amygdala is under complicated gonadal hormone regulation.

Amygdala↗
PubMed1988

Normal and cryptorchid castration.

Surgical exploration of the horse that has presumably had a normal castration or a previously successful cryptorchid surgery remains a distinct challenge. No hard and fast rules dictate a proper course of action for each case. If a horse was anesthetized for routine castration, discovered to have only one scrotal testis, had a brief exploratory on the nondescended side and was recovered, trauma to the inguinal region would probably be sufficiently minimal that an inguinal approach could be used at subsequent exploratory surgery. If the inguinal canal was extensively manipulated and the tail of the epididymis was inadvertently removed, however, one of the alternate approaches would be advisable. Where previous history is unknown, external and rectal palpation, hormonal assays, and careful evaluation of the scrotal/inguinal scars under anesthesia are advisable prior to proceeding with a specific course of action. As previously cited, "one hopes for the best but prepares for the worst." Where inguinal canals are being explored in the supposedly previously castrated horse that still has aggressive male behavior, the surgeon is searching for vaginal process and contents or the stump of the spermatic cord. If the stump is identified to suggest complete previous castration, the stump should contain cremaster muscle, parietal vaginal tunic, testicular vessels, and ductus deferens. If a second nonvascular tubular structure is found but no testicular vessels are found, the tail of the epididymis was inadvertently removed and assumed to be hypoplastic testis. This determination can be difficult to make on gross observation of the stump. Again, a thorough case workup helps one plan in advance for what should be found at surgery.

Animals↗
PubMed2006

Both soybean and kudzu phytoestrogens modify favorably the blood lipoprotein profile in ovariectomized and castrated hamsters.

The present study compared the hypolipidemic activity of kudzu phytoestrogens with that of soybean phytoestrogen in estrogen- and androgen-deficient hamsters. In the first experiment, ovariectomized hamsters (n = 37) were randomly divided into four groups (n = 9-10 each group). The first group was the control group, whereas the second group had the time-releasing estradiol-17beta subcutaneous (pellet) implants as a positive control. The third and fourth groups were orally administered soybean or kudzu phytoestrogen extracts (30 mg/kg of body weight) per day. In the second experiments, the first group of male hamsters (n = 9) received a sham operation, whereas the other three groups of male hamsters (n = 9 each) were castrated. The castrated control group received orally distilled water, whereas the second and third castrated groups were orally given 30 mg/kg soybean or kudzu phytoestrogen extracts. The results for the first experiment showed that the ovariectomized hamsters orally given soybean and kudzu phytoestrogen extracts had significantly decreased serum total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) with HDL cholesterol (HDL-C) being unaffected. The data from the second experiment demonstrated that administration of soybean but not kudzu phytoestrogen extracts decreased significantly serum TC. However, administration of kudzu phytoestrogens caused redistribution of cholesterol among lipoproteins, leading to a significant decrease in the ratio of non-HDL-C to HDL-C. It was concluded that both soybean and kudzu phytoestrogens could modify favorably lipoprotein profiles in ovariectomized and castrated hamsters.

Animals↗
PubMed2002

[Castration of male lambs and calves: explanations and comments of art. 65 TSchV].

Since September 1, 2001, castration of male calves and small ruminants in Switzerland is not allowed without anesthesia. The use of rubber rings for that purpose is forbidden. This change of the legislation has been claimed by the Swiss consumers and is aimed to increase the animal welfare. The current paper provides a review of the different techniques of anesthesia and castration that may be advocated in male ruminants. Sedation with xylazine and injection of lidocaine in the area of the base of the scrotum, followed by closed castration with the Burdizzo represents a safe technique for painfree castration of calves and lambs.

Anesthesia↗
PubMed1989

Effect of castration and testosterone in experimental models of depression in mice.

In the behavioral despair (forced swimming) test and in the tail-suspension test, long-term (30-32 days) castration significantly increased the duration of immobility in mice. Testosterone propionate (1 or 10 mg.kg-1.day sc for 4 days), although not affecting the duration of immobility in sham-operated mice, reduced the duration of immobility in castrated mice to within normal limits. Desipramine (20 mg/kg ip) decreased the duration of immobility both in sham-operated and in castrated animals. These results indicate that castration favors an inactive behavior and that testosterone, although having no "antidepressant" effect per se, is necessary for the male animal to cope normally with adverse environmental situations.

Affect↗
PubMed1998

Apoptosis during castration-induced regression of the prostate is Fos dependent.

Apoptotic cell death was shown to be accompanied or preceded by an elevated expression of the c-fos protooncogene and DNA binding activity of transcription factor AP-1. We used Fos-deficient mice to study the role of c-Fos during programmed cell death in the prostate. In normal mice apoptosis is induced in the prostate within 2-4 days after castration. Histological features of reduced secretory activity and morphological signs of programmed cell death become obvious. No apparent decrease in secretory activity and no epithelial cell death were observed in Fos-deficient animals after castration. Fragmentation of nuclear DNA was measured by in situ terminal transferase reaction. DNA fragmentation was observed in the prostate epithelium of control mice after castration whereas no similar fragmentation was found in Fos-deficient animals. After castration an AP-1 complex accumulated in the prostate of Fos deficient mice which mainly consists of FosB, Fra-2 and JunD whereas in control animals the AP-1 complex in addition contained c-Fos. Our data strongly suggest that c-Fos is required for programmed cell death of prostate epithelial cells.

Animals↗