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PubMed1986

Effects of unilateral castration on serum luteinizing hormone, follicle stimulating hormone, and testosterone concentrations in one-, two-, and three-year-old stallions.

The endocrine control of compensatory hypertrophy was investigated in 12 Morgan stallions, four each at one, two and three years of age. Half were assigned to be unilaterally castrated (UC) in January and half to remain intact (IN). Nine blood samples were taken from each stallion at half-hour intervals 30, 90, and 150 d after unilateral castration for radioimmunoassay of serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone. Mean serum LH concentration was greater (P<0.06) in UC than IN stallions; however, the difference was greatest at 30 d and least at 150 d. Serum LH was greater (P<0.01) in two- and three-year-olds than in one-year-olds. The mean log(10) for serum FSH concentration was greater (P<0.06) in UC than IN stallions. Mean serum testosterone concentrations were similar in UC and IN stallions for all sample days, suggesting that the single testes of the UC stallions produced as much testosterone as the two testes of the IN stallions. Two- and three-year-old stallions had greater (P<0.01) serum testosterone than one-year-old stallions. Unilateral castration of stallions was associated with a significant increase in serum LH and FSH concentrations and, perhaps, higher intratesticular testosterone, which may explain, in part, the compensatory hypertrophy noted in the remaining testis.

Journal Article↗
PubMed1996

The effect of surgical castration on lipid metabolism in premenopausal and postmenopausal women.

OBJECTIVE: To investigate the effect of endogenous estrogen on lipid and lipoprotein metabolism in premenopausal and postmenopausal women. DESIGN: Prospective randomized study. SETTING: Department of Obstetrics-Gynecology, Beilinson Medical Center and Tel-Aviv University Medical School, Israel. SUBJECTS: Twenty-seven women, 15 premenopausal and 12 postmenopausal, undergoing surgical castration (total abdominal hysterectomy and bilateral salpingo-oophorectomy). METHOD: Blood samples were drawn before the surgical intervention and after a 6-month interval. MAIN OUTCOME MEASURES: Assays were performed for estradiol, luteinising hormone and follicle-stimulating hormone, and triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol and total cholesterol/HDL as well as HDL/LDL ratio. RESULTS: No significant differences were found in both groups, before castration and after 6 months. A modest, but statistically significant, rise in triglycerides was observed in the premenopausal group. CONCLUSIONS: The serum lipid and lipoprotein profile encountered in premenopausal and postmenopausal women were unchanged 6 months after surgical castration. The clinical significance indicates that the effect of endogenous estrogen on lipid metabolism is doubtful and should be further investigated.

Adult↗
PubMed1986

Testosterone metabolism in the olfactory epithelium of intact and castrated male rats.

To study the ability of the olfactory epithelium (OE) to transform testosterone (T) into its active metabolites estradiol (E2) and dihydrotestosterone (DHT), and the influence of castration on this ability, 24 adult male rats were either castrated, and subsequently treated with oil or T, or sham operated. In all groups the in vitro conversion of T by the OE into E2 and DHT is relevant, demonstrating for the first time the presence of aromatase and of 5 alpha-reductase in this tissue. In particular conversion of T into E2 is lowered by castration and restored by T replacement, suggesting that aromatization in this tissue is androgen dependent. The ability of circulating T to influence morphological and physiological features of the OE suggests the hypothesis that androgens may vary the functioning of the olfactory apparatus and modulate the efficiency by which olfactory information is conveyed to the brain.

Animals↗
PubMed1988

Ultrastructural changes in the rat neurohypophysis following castration and testosterone replacement.

Ultrastructural changes in male rat neurohypophyses were studied 8 or 30 days after castration, with or without testosterone (T) replacement via capsule implants. Morphometric analyses determined the: (a) amount of neural contact at the basal lamina (BL) of the neurovascular contact zone, (b) average length of individual terminal contacts with the BL, (c) number of neurosecretory terminals per 100 micrograms of BL, and (d) mean number of enclosed axonal processes per pituicyte. Eight days after castration there was decreased neural/BL contact and increased pituicyte enclosure of neurosecretory processes, conditions associated with decreased hormone release. In contrast, T replacement resulted in increased individual nerve terminal length, a measure associated with increased hormone demand. This observation may indicate a stimulatory effect of continuous high-normal circulating levels of testosterone from the capsule implants. There were no differences from control in 30-day castrate rats, but the 30-day rats with T replacement showed morphological indications of increased hormone release. These consisted of increased neural contact with the BL apparently through a significant increase in the number of neurosecretory terminals per unit length of BL. These findings support studies showing a complex feedback interaction between circulating levels of testosterone and vasopressin release.

Animals↗
PubMed1991

The effect of neonatal exposure to DES and o,p'-DDT on pituitary responsiveness to GnRH in adult castrated rats.

While exposure of vertebrates to estrogens during early development has been shown to alter adult reproductive behavior, neuroanatomy, and neurophysiology, effects on gonadotropin secretion have not been studied. We conducted the present studies to assess the effects of neonatal exposure to xenobiotic estrogens on luteinizing hormone secretion in castrated adult rats. Rat pups were injected with either corn oil, 1 micrograms diethylstilbestrol (DES), or 0.5 mg o,p'-DDT on postnatal days 1 to 10, and castration was performed on day 21. On day 42 of life, GnRH (50 ng/kg) was administered via right heart catheters, and blood was sampled for LH at 0, 5, 10, 15, and 30 min. Neonatal exposure to DES in both males and females significantly decreased basal and GnRH-induced LH secretion throughout the sampling period in castrated adults. o,p'-DDT significantly suppressed initial LH levels and blunted GnRH-induced release in males at the 5 min interval, while in females it had no effect. These data show that early exposure to environmental estrogens alters adult pituitary response to GnRH. Our results suggest that sexually distinct effects of environmental estrogens occur and can be readily demonstrated in this experimental model.

Animals↗
PubMedDate not supplied

Effect of cromakalim on spontaneous activity of castrated rat vas deferens.

After castration rat vasa deferentia exhibited spontaneous activity. Cromakalim which acts by opening K+ channels has been shown to suppress this spontaneous activity following castration. Glibenclamide, a potent blocker of the ATP-sensitive K+ channels, inhibited this contrasting effect of cromakalim. The concentrations of cromakalim and glibenclamide that were employed are consistent with those active in different kinds of smooth muscle. The presented data are compatible with the hypothesis that castration decreases potassium conductance and that such an effect could be responsible for spontaneous activity.

Animals↗
PubMed2005

Castration induced changes in dog prostate gland associated with diminished activin and activin receptor expression.

This study was conducted to evaluate the effect of androgen ablation on dog prostate gland structure and the proliferation capacity of the prostatic cells and their association with the expression of Activin A and Activin RIIA receptor. The effect of androgen on the prostate gland was compared in intact and castrated dogs after one and two weeks. Specific primary antibodies were used to immunolocalize activin-A, activin receptor type II A and the proliferation marker (PCNA). The results showed that the glandular acini of the prostate gland of intact dogs are lined by tall columnar secretory cells and less abundant flattened basal cells and surrounded by a thin fibromuscular tissue. The cytoplasm of the glandular cells exhibited an intense immunoreaction for activin A and activin RIIA receptor while basal cells expressed PCNA. Castration induced a remarkable atrophy of the prostatic acini associated with a progressive loss of secretory epithelial cells, which showed a dramatic decrease to complete disappearance of Activin A and Activin RIIA receptor immunoreactions. The remaining cells of the atrophied acini continue to express PCNA and the inter-acinar fibromuscular tissue showed a remarkable increase in its mass and are induced to express PCNA. These results indicated that androgen is required for the survival of epithelial cells and to maintain growth-quiescent fibromuscular cells, while basal cell proliferation is androgen independent. The changes in the Activin A and Activin RIIA receptor localization and their association with the dynamic pattern of prostate gland regression after castration suggested that Activin A and Activin RIIA receptor expression are androgen dependent.

Activin Receptors, Type II↗
PubMed2006

The effects of soy extract on the uterus of castrated adult rats.

OBJECTIVE: The aim of this study was to evaluate the effects of different doses of a standardized soy extract on the uterus of castrated rats. METHODS: Fifty-six adult castrated female Wistar rats were randomly divided into seven groups (eight animals in each) that received: GI--drug vehicle (propylene glycol); GII--soy extract 10mg/kg per day; GIII--soy extract 50mg/kg per day; GIV--soy extract 100mg/kg per day; GV--soy extract 300mg/kg per day; GVI--soy extract 600mg/kg per day; GVII-conjugated equine estrogens (CEE) 200microg/kg per day. After 21 days of treatment, all animals were sacrificed and fragments of the uterine horns were immediately removed, fixed in 10% formaldehyde and submitted to routine histological techniques for morphometric study. The endometrial cell proliferation index was determined with the PCNA antibody PC-10 and expressed as the percentuals of the PCNA-positive nuclei relative to the total countings. Other fragments were immediately frozen in liquid nitrogen for RNA extraction and VEGF analysis using RT-PCR technique. RESULTS: The minimal dose of soy extract that produced a significant increase of the morphometric parameters was 100mg/kg (GIV). The maximum effects on endometrial and myometrial morphometry were detected in the groups treated with 300 and 600mg/kg of soy extract (groups V and VI) and CEE (GVII). The expression of PCNA in the endometrial epithelium and stroma was increased by treatment with 100-600mg/kg per day of soy extract (groups IV-VI) or with CCE (group VII). Doses equal to or higher than 50mg/kg of soy extract (groups III-VI) and CEE stimulated the expression of VEGF. CONCLUSION: The treatment of adult castrated rats during 21 days with doses of 100mg/kg per day or higher of soy extract may determine significant proliferation in the endometrium and myometrium.

Animals↗
PubMed2004

Involvement of serotoninergic mechanism in analgesia by castration and flutamide, a testosterone antagonist, in the rat formalin test.

Several studies have suggested that testosterone has a role in nociception. Recently, we have shown that castration and flutamide, a testosterone antagonist, induce analgesia in the late phase of formalin test, which is related to increase of 5-HT levels in the dorsal horn of the lumbar spinal cord. The aim of the present study was to investigate the effect of fluoxetine, a selective serotonin reuptake inhibitor, on castration and flutamide-induced analgesia in order to further explore the role of 5-HT systems in such analgesia. Four weeks after castration, there was an analgesia in the late phase of formalin test, and this was potentiated by acute (0.32 mg kg(-1) ip) treatment of fluoxetine. Furthermore, coadministration of fluoxetine (0.32 mg kg(-1) ip) and flutamide (10 mg kg(-1) ip) produced more antinociceptive effect than those animals receiving fluoxetine and flutamide alone. The analgesic effect of fluoxetine (0.32 mg kg(-1) ip) and flutamide (10 mg kg(-1) ip) was abolished by pretreatment with 5,7-DHT (100 microg/rat it) and naloxone (2 mg kg(-1) ip). In summary, our data suggest that fluoxetine and flutamide have antinociceptive effects in tonic inflammatory pain through functional alteration of serotonergic systems, and their effects are potentiated by coadministration. The possible role of opioidergic system in their antinociceptive effect cannot be neglected.

Analgesia↗
PubMed2006

Surveyed attitudes, perceptions and practices in Norway regarding the use of local anaesthesia in piglet castration.

The last two years piglet castration in Norway has been performed by veterinarians and with the use of anaesthesia. In order to evaluate this new policy, veterinarians and pig producers were asked to fill out a questionnaire regarding their experiences with the new castration practices. The answers showed that the piglets were most often castrated using a combination of subcutaneous and intratesticular administration of lidocaine with adrenaline at an average age of 10 days. The effect of the anaesthesia was regarded as good by 54% of the veterinarians and 19% of the producers. Post-operative complications were rare. The overall evaluation showed that two-thirds of the veterinarians, but only one-third of the pig producers were satisfied or very satisfied with the implemented policy. However, while two-thirds of the pig producer had a negative attitude to the policy before it was implemented, only one-third were dissatisfied after two years experience.

Agriculture↗
PubMed2006

The sexuality and social performance of androgen-deprived (castrated) men throughout history: implications for modern day cancer patients.

Androgen-deprivation therapy (ADT) via either surgical or chemical castration is the standard treatment for advanced prostate cancer (PCa). In North America, it is estimated that more than 40,000 men start ADT each year. The side effects of this treatment are extensive and include gynecomastia, erectile dysfunction, and reduced libido. These changes strongly challenge patients' self-identity and sexuality. The historical term for a man who has been castrated is 'eunuch', now a pejorative term implying overall social and sexual impotence. In this paper, we review key historical features of eunuch social performance and sexuality from a variety of cultures in order to assess the validity of contemporary stereotypes of the androgen-deprived male. Data were taken from secondary sources on the history of Byzantium, Roman Antiquity, Early Islamic societies, the Ottoman Empire, Chinese Dynasties, and the Italian Castrati period. This cross-cultural survey shows that castrated men consistently held powerful social positions that yielded great political influence. Many eunuchs were recognized for their loyalty, managerial style, wisdom, and pedagogical skills. Furthermore, rather than being consistently asexual and celibate, they were often sexually active. In certain cultures, they were objects of sexual desire for males, or females, or both. Collectively, the historical accounts suggest that, given the right cultural setting and individual motivation, androgen deprivation may actually enhance rather than hinder both social and sexual performance. We conclude that eunuch history contradicts the presumption that androgen deprivation necessarily leads to social and sexual impotence. The capabilities and accomplishments of eunuchs in the past gives patients on ADT grounds for viewing themselves in a positive light, where they are neither socially impotent nor sexually chaste.

Androgen Antagonists↗
PubMed2004

Testosterone-stimulated weanlings as an alternative to castrated male rats in the Hershberger anti-androgen assay.

We showed previously that stimulation of weanling male rats with the synthetic androgen 17-methyltestosterone (17MT) caused premature growth of the sex accessory tissues such that the activity of the two anti-androgens flutamide and DDE could be demonstrated (Regul. Toxicol. Pharmacol. 35 (2002) 280). We suggested that that protocol should be evaluated as an alternative to the castrated male rat Hershberger assay. In the present paper we justify changing the assay protocol to use testosterone propionate (TP), in place of 17MT, as the stimulating androgen. This change enables biochemical formation of dihydrotestosterone from testosterone, a conversion not possible when using 17MT. This change in the protocol enables detection of the testosterone-5-reductase inhibitor finasteride. The modified TP-stimulated weanling male rat assay is shown to have similar sensitivity to that of the castrated male rat Hershberger assay in detection of the anti-androgens flutamide, procymidone, vinclozolin, and DDE, and of the biochemical inhibitor finasteride. The anti-androgen linuron and the anabolic steroid trenbolone were also detected as positive by the TP-stimulated weanling male assay. It is suggested that this modified assay for anti-androgens should be validated as an alternative to the Hershberger assay, thereby reducing animal stress by obviating the need for surgical castration.

Androgen Antagonists↗
PubMed2003

Castration does not decrease nonreproductive aggression in yearling male European starlings (Sturnus vulgaris).

In the nonbreeding season, some bird species express high levels of aggression despite basal plasma testosterone (T) concentrations. Consequently, nonreproductive aggression is believed to be independent of plasma T. In the present study, we investigated the effect of castration on nonreproductive aggressive behavior in yearling male European starlings (Sturnus vulgaris). We paired castrated (Cx) with control (C) males in dyadic trials during three test periods (December, January-February, and March-April), and by using an infrared camera, we defined which male was the most aggressive one when both males were competing over access to a nest box to roost in. During each of the three periods, Cx males behaved more aggressively than C males but differences between groups did not reach significance. When analyzing the results of the three periods together, Cx males were found to be significantly more aggressive than C males. Likewise, when considering only the second and third period (when plasma T levels of C males were significantly higher than those of Cx males) the same result was obtained. Furthermore, in the third period, aggression tended to be lower than in the first and second period, although T concentrations of C males were highest in this period. Our data thus clearly show that nonreproductive aggression in yearling male starlings is independent of gonadal sex steroids and suggest it even increases by castration.

Aggression↗
PubMed2000

Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making.

OBJECTIVES: Based on methods introduced in the late 1960s and no longer used, serum testosterone level in men after surgical castration was reported to be 50 ng/dL or less. Radioimmunoassay and, subsequently, chemiluminescent methods have supplanted the early analytic methods because of their improved accuracy and ease of testing. The purpose of this study was to define the castrate testosterone level in the era of chemiluminescent testing. METHODS: After bilateral orchiectomy, serum testosterone (total) levels were measured prospectively in 35 prostate cancer patients. RESULTS: The median testosterone value in this patient cohort was 15 ng/dL (0.5 nmol/L; 95% confidence interval 12 to 17 ng/dL). CONCLUSIONS: In a contemporary series, castrate testosterone should be defined as less than 20 ng/dL (0.7 nmol/L). The important biologic and economic implications are discussed.

Aged↗
PubMed1993

The effect of androgen and estrogen on secretory epithelial cells and basal cells of the rat ventral prostate after long-term castration.

After long-term castration, rats were injected with cotton seed oil, testosterone- and estradiol-17 beta-cypionate (CS, TC and EC). The height of the epithelial cells of the ventral prostates from the castrated rats increased after TC and EC-injection. The secretory and basal cells formed two layers of epithelium, an inner layer near the lumen with pale nuclei and another layer with dark nuclei. These two layers could result from a reduction of secretory epithelial cells. Castration decreased the ratio of secretory cells to basal cells (S/B). TC-injection increased the ratio of S/B because of the secretory epithelial cell growth. Longer dark cells may be transient cells, appearing during the differentiation of basal cells into secretory epithelial cells. A sheet branching off from the basal lamina was observed. Androgen may stimulate the synthesis of the lamina, but whether it induces the synthesis or turnover of the basal lamina has not been established. EC increased the ventral prostatic weight and secretory epithelial cell height and induced the appearance of crystalline granules. Increase in S/B ratio may result from an increase in the secretory epithelial cells, but not from basal cell multiplication due to squamous metaplasia. The ratio is significantly correlated to the weight of the ventral prostate, but not to the secretory epithelial cell height. Its value could indicate the multiplication of secretory epithelial cells, differentiation of basal cells into epithelial cells, or both. It is probable that basal cells do not change in number, but control the size of the rat ventral prostate in response to the hormone level.

Animals↗
PubMed2003

[The effect of a pain medication in bloodless castration of male calves on the concentrated feed intake, weight gain and serum cortisol level].

Since September 2001, castration of male calves in Switzerland is not allowed without anesthesia. The use of rubber rings for this purpose is forbidden. It was the goal of this study to describe the effect of a non-steroidal antiinflammatory drug, administered additionally to sedation and local anesthesia, in clamp-castrated (Burdizzo) calves of 110 to 160 kg of body weight. Plasma fibrinogen concentration, white blood cell count, serum cortisol concentration, scrotal swelling, concentrate intake and weight gain were evaluated. A positive effect after administration of a NSAID was obvious for the serum cortisol concentration, the concentrate intake within the first 3 days after castration and scrotal swelling.

Animals↗
PubMed1997

Internucleosomal DNA fragmentation is not obligatory for castration induced rat ventral prostate cell apoptosis in vivo.

Castrated male rats were treated with the reversible S1-phase cell cycle blocking drug, mimosine, and the effects of this drug on prostate cell apoptosis was characterized. At a single dose of mimosine (25 mg/kg/day), we found that the internucleosomal DNA fragmentation associated with apoptosis was partially suppressed in the rat ventral prostate at all early time points (24, 48 and 72 h) analyzed post-castration. This suppression was dose-dependent, and treatment with mimosine up to 150 mg/kg/day was sufficient to reduce the internucleosomal DNA fragmentation in the prostate by 90% at 72 h post-castration. Intriguingly, this drug did not suppress the induction of mRNAs for several apoptosis-associated gene products in the ventral prostate gland (bcl-2, p53, TGF-beta and SGP-2/clusterin). Moreover, this treatment did not suppress the histological appearance of apoptotic bodies in the ventral prostate detectable by fast green staining of thin sections of tissue. The apoptotic bodies present in mimosine-treated regressing ventral prostate tissues, however, were refractory to labeling by the in situ gap labeling method, further demonstrating lack of nuclear DNA fragmentation in the condensed nuclei of apoptotic cells. In summary, the cell cycle-blocking drug mimosine does not appear to affect the rate of apoptosis in the regressing rat ventral prostate gland. However, this drug was capable of suppressing the nuclear DNA fragmentation associated with androgen-regulated prostate cell apoptosis. These results support the concept that nuclear DNA fragmentation is not obligatory for apoptosis. Additionally, they imply that cell cycle movement from the G1/S-phase boundary might be important for the terminal DNA degradation associated with androgen-regulated prostate cell apoptosis.

Journal Article↗
PubMed1999

Maximum androgen-blockade with medical or surgical castration in advanced prostate cancer: A meta-analysis of nine published randomized controlled trials and 4128 patients using flutamide.

With the recent Southwest Oncology Group (SWOG) publication of their metastatic prostate cancer clinical trial results, which concluded that orchiectomy and flutamide as maximal androgen blockade (MAB) therapy vs orchiectomy alone does not significantly improve survival (NCI 0105), and the 1989 publication from the same cooperative group indicating a 24% improvement in survival for MAB therapy with leuprolide and flutamide versus leuprolide alone (NCI 0036), clinicians may well be undecided about the likelihood of clinical benefits with flutamide in combination with medical or surgical castration. To better characterize this important therapeutic decision, we assessed the survival benefit of MAB therapy with flutamide through a meta-analysis of up-to-date information from studies reported/conducted from 1989 through 1998. All peer-reviewed published randomized controlled trials comparing treatment with flutamide plus either lutenizing hormone releasing hormone (LhRH) agonists or orchiectomy as MAB treatment with LhRH or orchiectomy alone were included. The primary objective of the study was to form a combined estimate and confidence interval for the hazard ratio (as measured by the relative risk (RR) of survival in a comparison of castration vs MAB) summarizing the effect of flutamide treatment on overall survival. Directly extracted estimates of the log hazard ratio were used if available (1 study); if not, either an estimate of the RR based on a reported P-value from a log rank test (7 studies) or a discrete proportional hazards approximation based on reconstructed annual life tables for the treatment arms (1 study) were used. Nine studies with 4128 patients with advanced prostate cancer were included in these analyses. Pooled estimates demonstrated a 10% improvement in overall survival with flutamide as MAB therapy (relative risk (RR)=0.90, 95% Confidence Interval=0.79, 1.00). The currently available updated evidence from randomized trials shows a 10% benefit in overall survival with flutamide as MAB therapy in comparison to conventional castration, almost identical to the estimate reported in the recently published Southwest Oncology Group Study (NCI 0105).

Journal Article↗