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PubMed2001

Biocompatibility of steroid-HA delivery system using adult castrated rams as a model.

The objective of this study was to analyze the fibrous tissue surrounding dihydrotestosterone (DHT loaded HA devices implanted subcutaneously (S/C) in adult castrated rams. The microcrystals of HA were prepared by following standard laboratory procedure. Housing, surgical implantation and bleeding procedure of all rams used in this study was conducted according to the NIH guideline and approval of UCUCA. A total of 11 rams were castrated by elastrator rings within a week after birth. At 7 months of age the animals were randomly divided into three groups. Group 1 rams (n = 4) were not treated and served as the control group. Rams in group 2 (n = 3) were implanted s.c. with two HA capsules (80 mg DHT/capsule). Each ram (n = 3) in group 3 was implanted with two empty HA capsules and served as a sham group. All animals were housed together throughout this study and water, high quality hay and grain were given ad libitum. The sterilized ceramics were inserted S/C through a single incision using standard aseptic surgical techniques. Gross, radiographic and histological examinations of the site of implantation did not show any untoward reactions during the entire investigation. Histopathological evaluation have revealed that all HA implants were encapsulated with hyaline fibrous tissue at the end of two weeks, and the degree of encapsulation increased with time. Results collected from this investigation showed that the passage of DHT through HA capsules started within 3 days after implantation. Furthermore, sustained delivery of DHT by means of HA devices at levels ranging between 1.4-3.3 ng/ml imposed continuous negative feedback on post-castration rise in serum LH and FSH secretion. Representative retrieved implants showed slight degradation of the implant (27% +/- 38) and increased erosion at the sharp edges with time was observed. Light and electron microscopic evaluation demonstrated that at the end of four weeks postimplantation, a well developed granulation tissue is seen surrounding the implants. The thin developing fibrous capsule infiltrated with macrophages and numerous small and large capillaries were observed. A well-developed fibrous capsule formed at 6 months postimplantation. Four different layers were observed: (i) the HA tissue layer contains macrophages, some mononuclear leukocytes, and fibroblasts indicative of the chronic inflammatory responses, (ii) the fibrous capsule layer is composed of longitudinally oriented fibroblasts and mature collagen fibers, (iii) the vascularization layer contains numerous large and small capillaries, and (iii) the outer side of the fibrous capsule predominately composed of adipose tissue. Data obtained from this study suggest that lack of vascularization at the immediate HA tissue layer and the fibrous capsule layer may function to retard the rapid release of DHT from the HA implants. This retardation of DHT release from HA implants by the formation of fibrous capsule is needed to compensate for the macropores formed during the biodegradation of the implants.

Adipose Tissue↗
PubMed2001

Castration-induced expression of caspase-1 in epithelia of accessory sex organs in male rats.

AIM: As an attempt to clarify the molecular basis of castration-induced apoptosis, this study was undertaken to demonstrate the expression of caspase-1 in male accessory sex organs of rats. METHODS AND RESULTS: cDNA of rat caspase-1 was cloned by reverse transcription-polymerase chain reaction from the ventral prostates. The open reading frame predicts 402 amino acids, which shows more than 91% and 63% identity to those of mouse and human, respectively. Northern analyses demonstrated the presence of castration-induced up-regulation of the 1.6 kb transcript in the ventral prostate and the seminal vesicles. Finally, the authors demonstrated the caspase-1 transcripts in the epithelia of these tissues by in situ hybridization analyses. CONCLUSION: Castration induces the expression of caspase-1 transcripts in the epithelia of ventral prostate and seminal vesicle. These observations suggest a possible role of caspase-1 in apoptosis in male accessory sex organs.

Amino Acid Sequence↗
PubMed2001

Momentary increase in plasma calcitonin gene-related peptide is involved in hot flashes in men treated with castration for carcinoma of the prostate.

PURPOSE: In women the vasodilatory neuropeptides calcitonin gene-related peptide and neuropeptide Y seem to be involved in menopausal hot flashes. We assessed whether plasma calcitonin gene-related peptide and neuropeptide Y change during hot flashes in men after castration. MATERIALS AND METHODS: We evaluated 10 men 61 to 81 years old who underwent castration due to cancer of the prostate and had frequent hot flashes for changes in plasma calcitonin gene-related peptide and neuropeptide Y during 1 day at the outpatient clinic. At least 5 blood samples were obtained between flashes and 4 were obtained during each flash. The samples were analyzed for calcitonin gene-related peptide and neuropeptide Y using radioimmunoassay technique. Hot flashes were objectively recorded by measuring peripheral skin temperature and skin conductance. RESULTS: Plasma calcitonin gene-related peptide increased 46% (95% confidence interval 21 to 71) during flashes in the 6 men in whom it was measurable. This change was statistically significant (p = 0.028). The concentration of neuropeptide Y was below the detection limit. Skin conductance and temperature increased significantly during flashes. CONCLUSIONS: Calcitonin gene-related peptide is involved in the mechanisms of hot flashes in men who underwent castration due to prostate carcinoma. Thus, there may be a similar mechanism of hot flashes in women and in men deprived of sex steroids.

Aged↗
PubMed1998

[Kinetic effect of testosterone or estradiol on iodine absorption in castrating rat intestine].

OBJECTIVE: To observe the effect of testosterone or estradiol on iodine absorption in rat intestine. METHOD: 50 male adult Wistar rats were divided into 5 groups randomly. 50 females were divided into another 5 groups. Among them, 4 groups were bilaterally testectomized or ovariectomized, 1 group was sham-operated. 7 days after operation, the castrated rats received testosterone (male rats) or estradiol (female rats) at different dosages by intramuscular injection for three days. Then the kinetics of iodine absorption in jejunum and ileum were observed by perfusion in situ. When finished, serum were obtained for detecting TSH, T4 and testosterone or estradiol. RESULTS: In castrated male rats, the value of K12 reduced, K21 increased, K02 reduced, and SP1/2 (the half time of the slow phase) prolonged, implying that the ability of iodine absorption reduced. It reflected that testosterone could promote iodine absorption in intestine in physiological condition. In castrated female rats, the situation was different from that in male rats, the value of K12 increased, K21 reduced, K02 increased, and SP1/2 shortened in jejunum, implying that the ability of iodine absorption increased. It reflected that estradiol could inhibit iodine absorption in intestine in physiological condition. The levels of serum TSH and T4 were not changed significantly in this experiment. CONCLUSION: In physiological condition, testosterone can promote iodine absorption, while estradiol has the inhibiting effect. The results indicate that gonadol hormone maybe one factor which can influence iodine absorption in intestine. It may explain the phenomenon that the incidence of goiter is different between males and females partly.

Animals↗
PubMed2002

Tolerability assessment of maximal androgen blockade with 50 mg daily of bicalutamide and castration in patients with advanced prostate cancer.

BACKGROUND: Androgen is the most important growth factor for the development and growth of prostatic adenocarcinomas. For patients with advanced prostate cancer, hormonal manipulation including castration and antiandrogen therapy is a well-established mode of treatment. The choice of hormonal therapy for prostate cancer depends not only on the desired progression-free and overall survival, but also on the patient's quality of life, treatment costs, and treatment toxicities. METHODS: This was an open, non-comparative trial to determine the tolerability of 50 mg bicalutamide (Casodex) in combination with castration; we also investigated whether the prostate-specific antigen (PSA) rates of change at weeks 4 and 12 were indicative of an increased risk of progression. RESULTS: Thirty-seven patients were enrolled in the study from December 1996 to June 1999 in Chang Gung Memorial Hospital, Taoyuan. The overall incidence rate of adverse events was 27%. The most frequent adverse event was hot flushes (5.4%). The rate of overall disease response was 85.3%. No evidence was found for any predictive relationship between serum PSA concentration and risk of progression. CONCLUSION: The overall results indicate that bicalutamide administered as a 50-mg daily dosage in combination with castration is a well-tolerated therapy for the treatment of patients with advanced prostate cancer.

Aged↗
PubMed2003

Castration-induced increases in insulin-like growth factor-binding protein 2 promotes proliferation of androgen-independent human prostate LNCaP tumors.

Activation of alternative growth factor pathways after androgen withdrawal is one mechanism mediating androgen-independent (AI) progression in advanced prostate cancer. Insulin-like growth factor (IGF) I activation is modulated by a family of IGF binding proteins (IGFBPs). Although IGFBP-2 is one of the most commonly overexpressed genes in hormone refractory prostate cancer, the functional significance of changes in IGF-I signaling during AI progression remains poorly defined. In this article, we characterize changes in IGFBP-2 in the LNCaP tumor model after androgen withdrawal and evaluate its functional significance in AI progression using gain-of-function and loss-of-function analyses. IGFBP-2 mRNA and protein levels increase 2-3-fold after androgen withdrawal in LNCaP cells in vitro in LNCaP tumors during AI progression in vivo. Increased IGFBP-2 levels after castration were also identified using a human prostate tissue microarray of untreated and posthormone therapy-treated prostatectomy specimens. LNCaP cell transfectants that stably overexpressed IGFBP-2 progressed more rapidly after castration than control tumors. Antisense oligonucleotides (ASOs) targeting the translation initiation site of IGFBP-2 reduced IGFBP-2 mRNA and protein expression by >70% in a dose-dependent and sequence-specific manner. ASO-induced decreases in IGFBP-2-reduced LNCaP cell growth rates and increased apoptosis 3-fold. LNCaP tumor growth and serum prostate-specific antigen levels in mice treated with castration plus adjuvant IGFBP-2 ASOs were significantly reduced compared with mismatch control oligonucleotides. Increased IGFBP-2 levels after androgen ablation may represent an adaptive response that helps potentiate IGF-I-mediated survival and mitogenesis and promote androgen-independent tumor growth. Inhibiting IGFBP-2 expression using ASO technology may offer a treatment strategy to delay AI progression.

Androgens↗
PubMed1976

Effect of d-6-methyl-8-ergoline-i-ylacetamide (Deprenon) on the FSH content of the pituitary in castrated female rats.

The authors studied the effect of Deprenon (D-6-methyl-8-ergoline-I-acetylamide tartrate) on the FSH content of the adenohypophysis of female rats which had been castrated 3 and 6 weeks previously. The FSH content, determined by the method of Johnson and Naqui (1970), is expressed at the mean weights of the recipients' ovaries compared with a group given only 30 I.U. HCG. Within 30 min after administration, a single peroral dose of 0.5 mg Deprenon/kg produced a drop in the pituitary FSH content. This was not very pronounced 3 weeks after castration, but was highly significant 6 weeks after castration, when the amount of FSH in the control animals' pituitaries rose.

Acetamides↗
PubMed1992

Decline of vasopressin immunoreactivity and mRNA levels in the bed nucleus of the stria terminalis following castration.

Vasopressinergic (VP) neurons in the bed nucleus of the stria terminalis (BNST) of the rat are regulated by gonadal steroids. Gonadectomy causes the projections of the BNST to lose their VP immunoreactivity gradually over a period lasting more than 2 months. Here we have compared the rate of decline of VP mRNA and VP immunoreactivity in the BNST of adult male rats following castration. In experiment 1, the peak number of VP-immunoreactive cells and the level of VP gene expression were compared in sham-operated controls and at 1, 3, or 8 weeks postcastration. The number of VP-immunoreactive cells was not decreased at 1 week postcastration but was significantly reduced (p less than 0.0001) at 3 and 8 weeks postcastration. VP gene expression declined more rapidly, and both the total number of labeled cells (p less than 0.0001) and the average number of grains per cell (p less than 0.01) were significantly reduced by 1 week postcastration. No VP-expressing cells were detectable at 3 or 8 weeks. The difference in the rate of decline in the number of cells labeled by the two techniques following castration did not appear to be due to colchicine pretreatment. In experiment 2, VP mRNA in the BNST was compared in sham-operated controls or at 1, 3, or 7 d postcastration. A significant decrease (p less than 0.01) in the average number of grains per cell was detectable by just 1 d following castration, and the number of labeled cells was significantly reduced (p less than 0.001) by 3 d postcastration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Interaction of androgens and prolactin on prostatic enzymes of the pyruvate-malate cycle involved in lipogenesis in castrated mature monkey, Macaca radiata.

Effects of androgens, prolactin (Prl) and bromocriptine (Br) on the specific activities of prostatic (caudal and cranial) enzymes of the pyruvate-malate cycle were studied in castrated mature bonnet monkeys. Castration decreased the activity of NADP+ isocitrate dehydrogenase (ICDH), ATP citrate lyase, malate dehydrogenase (MDH), malic enzyme and fatty acid synthase (FAS). Administration of testosterone propionate (TP)/dihydrotestosterone (DHT) increased the activities of all these enzymes in both lobes. Malate dehydrogenase maintained normal activity. Prl also had a stimulatory effect on the enzymes and was further enhanced when Prl was given in combination with TP/DHT. Unlike Prl, bromocriptine treatment inhibited all the enzymes in both lobes. Thus, prolactin was found to have a direct as well as a synergistic effect with androgens on enzymes of the pyruvate-malate cycle in the prostate of castrated mature monkeys.

ATP Citrate (pro-S)-Lyase↗
PubMed2005

[Microcirculation changes in the ventral prostates of rats after castration].

OBJECTIVE: To study the microcirculation changes in the ventral prostates of rats after castration and the role of microcirculation during the apoptosis of prostatic cells. METHODS: Thirty-six male adult rats were randomized to 6 groups: one was taken as the control, while the other 5 underwent measurement of the microcirculation in vivo by a D95 physiological signal acquisition system 12 h, 24 h, 72 h, 7 d and 14 d respectively after castration, and then were perfused with Chinese ink to trace the microvessels of the prostates. RESULTS: The microcirculation of the rats'prostates changed dramatically following castration. The diameter and density of the microvessels, especially in the distant and mediate ducts of the prostates, decreased dramatically, and so did the bloodflow velocity. CONCLUSION: The microcirculation plays a role during the process of apoptosis of prostatic cells, and might be the mechanism of " apoptosis shift".

Animals↗
PubMed2005

[Risking more freedom? Cyproterone acetate, sexual offenders and the German "Law on voluntary castration and other methods of treatment", 1960-1975].

Shortly after the fall of the National Socialist regime efforts were made in the Federal Republic of Germany to legislate anew on sterilisation and castration. For some experts, in particular sexologists and forensic psychiatrists in Hamburg, the question of the "treatment" of sexual offenders soon played a major role. In another research context an endocrinological substance showing anti-androgenic effects was synthesised in 1961 at the Schering AG in Berlin. In 1966 this substance, cyproterone acetate, was used for the first time to subdue the sexual drive. During parliamentary debates on a reintroduction of castration as a method of treatment for sexual deviations the advocates of cyproterone acetate succeeded in "inserting" their expertise into the "law on voluntary castration and other methods of treatment", which was adopted by the German Bundestag in January 1969. This paper discusses the interface between applied pharmacology, forensic psychiatry and sexology, and the politics leading to this law.

Cyproterone Acetate↗
PubMed1991

Effects of bacterial infection and castration on prostatic tissue zinc concentration in dogs.

An Escherichia coli bacterial prostatitis was experimentally induced to determine the effect of bacterial infection on prostatic tissue zinc concentrations in castrated and gonadally intact male dogs. Five of the 22 mixed-breed dogs (group 1) had no culture evidence of infection 2 weeks after the instillation of bacteria into the prostate gland. The remaining 17 infected dogs were allotted to 2 groups; 1 group of dogs was subjected to castration (group CA, 7 dogs), and the other group of dogs was subjected to sham operation (group SO, 10 days). The groups were divided into groups of dogs with prostatic infection at necropsy (groups CA-I and SO-I), and those dogs without prostatic infection at necropsy (groups CA-N and SO-N). Urine, prostatic fluid, and prostatic tissue (week 0, 7, +/- 12) specimens were obtained for bacteriologic culturing to determine whether prostatic infection was present. Prostatic tissue was obtained at necropsy (week less than 6, 7, or 12) for analysis of zinc concentration by atomic absorption spectrophotometry. The logarithmic mean prostatic tissue zinc concentrations were compared between groups. Group CA had a significantly lower prostatic zinc concentration than all other groups. Zinc concentrations were not statistically different between any of the other groups. Castration did decrease the prostatic tissue concentration of zinc, a known natural antibacterial factor. However, resistance to infection and resolution of infection were not correlated with prostatic tissue zinc concentrations in this experimental model.

Analysis of Variance↗
PubMed1990

Influence of prolactin, androgens and bromocriptine on seminal vesicular and prostatic adenosine triphosphatases in castrated adult monkeys Macaca radiata.

E ects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT) and the combinations of these androgens with PRL/Br on specific activities of adenosine triphosphatases (ATPases) of seminal vesicles and cranial and caudal prostates were studied in castrated adult bonnet monkeys. Castration decreased all ATPases (sodium/potassium, magnesium and calcium dependent) of seminal vesicles and both the lobes of prostate. PRL restored the normal activities of all ATPases in both the organs. Br given alone decreased all ATPases of prostate but caused no significant alteration, particularly calcium dependent ATPases of seminal vesicles and caudal prostate. TP/DHT replacement restored all ATPases of both the organs to the normal levels. PRL + TP/DHT further enhanced all the ATPases activities of all the regions studied. Br + TP/DHT decreased all ATPases but it did not produce any alteration in the calcium ATPases of seminal vesicles. The results suggest that prolactin facilitates membrane transport enzymes in the cranial and caudal prostate and seminal vesicles of adult castrated bonnet monkeys.

Adenosine Triphosphatases↗
PubMed1990

[Effect of castration on bone mineral metabolism in rats].

We have tried to experimentally determine what effect castration is going to have on rats bone and on the main mineral bone regulatory hormones. Twenty ovariectomized female rats and their age and weight matched controls were used. Parathormone, calcitonin, osteocalcin and serum calcium levels were determined as well as mineral bone content and head of femur density. Castration produces, in rat, a marked decrease in circulating calcitonin, parathormone (PTH) and bone density, with no changes in mineral bone concentration. Finally, castration produces a slight increase in osteocalcin serum levels although without a statistical value.

Animals↗
PubMed1986

Multiple phenotypes of prostatic glandular cells in castrated dogs after individual or combined treatment with androgen and estrogen. Morphometric, ultrastructural, and cytochemical distinctions.

To demonstrate a potential for multidirectional differentiation in mature prostatic epithelium, 17 beta-estradiol 17-cyclopentylpropionate (ECP) and 5 alpha-androstane-3 alpha, 17 beta-diol dipropionate (3 alpha-diol DP) were administered individually and in combination to castrated dogs. Quantitative ultrastructural and cytochemical methods were used to distinguish phenotypes of glandular cells in the various hormonal environments. Castration-induced glandular cell regression was accompanied by an increased nuclear to cytoplasmic ratio; by enhanced keratin positivity, expressed as dispersed immunolabeled tonofilaments; and by an absence of peanut agglutinin (PNA) binding sites on luminal membranes. Administration of ECP resulted in squamous metaplasia as well as hypertrophy of the glandular epithelium. The hypertrophied estrogen-modified glandular (EMG) cells were characterized by a new population of small (0.29 micron in diameter) secretory granules, bundles of tonofilaments, and PNA-positive luminal membranes. Treatment of castrated dogs with 3 alpha-diol DP produced a greater epithelial hypertrophy than ECP. These cells were characterized by larger (0.49 micron in diameter) secretory granules, dispersed tonofilaments, and no detectable PNA receptors. Joint administration of ECP and 3 alpha-diol DP caused a florid response including squamous metaplasia and hypertrophy of the glandular epithelium which was associated with the emergence of a novel phenotype in androgen-estrogen modified glandular (A-EMG) cells. In A-EMG cells, secretory granules were similar in size to those found in 3 alpha-diol DP-dominated epithelium whereas tonofilaments often appeared in bundles and luminal membranes were PNA positive, i.e., features found in EMG cells. Our results indicate that atrophic canine prostatic glandular cells possess pluripotentiality of response to sex hormones.

Androgens↗
PubMed1989

[Effect of estrogen replacement therapy on the serum osteocalcin level in the postmenopausal and castrated women].

Osteocalcin (OC), the major noncollagenous bone protein, is a vitamin K-dependent protein which is synthesized in osteoblasts. Serum OC is increased in patients with certain metabolic bone diseases, but little is known about the effects of menopause, castration, and the estrogen-replacement therapy on serum OC. In this study, we attempted to determine the serum OC level before and after menopause and castration, and the effects of estrogen on serum OC were also studied. Mean serum OC in women who underwent menopause or castration within 5 years was 4.56 +/- 1.74 ng/ml (mean +/- SD) and the concentration was significantly higher than that of premenopausal women. Serum OC was then, transiently reduced but increased again when estrogen deprived conditions lasted for more than 10 years. Estrogen replacement therapy (conjugated estrogen 0.625 mg/day for 6 months) could decrease not only serum Ca. P and ALP but also the serum OC from 4.45 +/- 1.40 to 2.97 +/- 1.43 ng/ml (p less than 0.001). There was a significant correlation between the percent changes in serum OC and ALP before and after estrogen administration (r = 0.60, p less than 0.05).

Adult↗
PubMed1986

[Subcutaneous grafts of fresh or cryopreserved testis in castrated rats and mice: comparison of the histologic aspects of the grafts].

In the castrated rat, only testis taken in one to two week-old donors observed three months after sub-cutaneous isograft contain a well developed interstitial tissue and some seminiferous tubules with germinal cells. On the contrary in castrated mice, testicular grafts taken in adult animals show some Leydig cells and degenerating seminiferous tubules. These grafts permit the restoration of androgenic activity in previously castrated recipients.

Animals↗
PubMed1988

Effects of castration and antiandrogens (RU 23908 and cyproterone acetate) on glandulain activity and on the secretory epithelium of the rat submandibular gland.

1. The influence of hormones on the submandibular gland of rodents has attracted more attention since the observation of the sexual dimorphism of these organs. Androgens enhance both the development and the secretory activity of the gland. 2. In the present investigation we have studied the differences in wet weight, protein content, glandulain activity and morphometry of granular convoluted tubules of submandibular glands excised from control, castrated and antiandrogen-treated (RU 23908 or cyproterone acetate) male adult albino rats. 3. Castration and antiandrogenic treatment did not affect the wet weight or protein content of the organs. Castration or treatment with RU 23908, but not treatment with cyproterone acetate, decreased glandulain activity and the height of the secretory epithelium of granular ducts. 4. The morphology and glandulain activity of submandibular gland granular ducts do not seem to be related solely to plasma testosterone concentration. Different hormonal treatments are needed to identify other factors implicated in the phenomenon.

Aminopeptidases↗