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PubMed2006

Persistent intraprostatic androgen concentrations after medical castration in healthy men.

CONTEXT: The impact of serum androgen manipulation on prostate tissue hormone levels in normal men is unknown. Studies of men with prostate cancer have suggested that prostatic androgens are preserved in the setting of castration. Tissue androgens might stimulate prostate growth, producing adverse clinical consequences. OBJECTIVE: The objective of the study was to determine the effect of serum androgen manipulation on intraprostatic androgens in normal men. DESIGN: Thirteen male volunteers ages 35-55 yr (prostate-specific antigen < 2.0 ng/ml; normal transrectal ultrasound) were randomly assigned to: 1) a long-acting GnRH-antagonist, acyline, every 2 wk; 2) acyline plus testosterone (T) gel (10 mg/d); or 3) placebo for 28 d. Serum hormones were assessed weekly. Prostate biopsies were obtained on d 28. Extracted androgens were measured by RIA, and immunohistochemistry for androgen-regulated proteins was performed. RESULTS: The mean decrease in serum T was 94%, whereas prostatic T and dihydrotestosterone levels were 70 and 80% lower, respectively, in subjects receiving acyline alone compared with controls (P < 0.05). Despite this decrease in prostate androgens, there were no detectable differences in prostate epithelial proliferation, apoptosis, prostate-specific antigen, and androgen receptor expression. CONCLUSION: In this small study of healthy subjects, despite a 94% decrease in serum T with medical castration, intraprostatic T and dihydrotestosterone levels remained 20-30% of control values, and prostate cell proliferation, apoptosis, and androgen-regulated protein expression were unaffected. Our data highlight the importance of assessing tissue hormone levels. The source of persistent prostate androgens associated with medical castration and their potential role in supporting prostate metabolism deserves further study.

Adult↗
PubMed1990

Castration enhances expression of glial fibrillary acidic protein and sulfated glycoprotein-2 in the intact and lesion-altered hippocampus of the adult male rat.

This study concerns effects of the testes on two macromolecules in the rat hippocampus that were previously not known to be responsive to this endocrine axis. Castration for 3 weeks elevated the expression of glial fibrillary acidic protein (GFAP) and sulfated glycoprotein-2 (SGP-2) in male rat hippocampus, as shown by Northern blots and immunocytochemistry. SGP-2 mRNA was colocalized with GFAP, implying increased prevalence in astrocytes after castration. During hippocampal responses to deafferentation by entorhinal cortex lesions that damage the perforant path and induce synaptic reorganization, both mRNA and protein for SGP-2 and GFAP increase. Moreover, prior castration had an additive effect with entorhinal cortex lesions in the increase in GFAP and SGP-2 mRNA. These data suggest that testicular hormones regulate hippocampal astrocyte activity in intact adult rats as well as during synaptic reorganization in response to deafferenting lesions.

Animals↗
PubMed2000

Estrogen agonist (zeranol) treatment in a castrated male lamb model: effects on growth and bone mineral accretion.

The mechanism of estrogen's action on bone mineralization in children has received little attention. Our objective was to determine the effect of time (developmentally) and duration of exposure to an estrogen agonist (zeranol) on bone growth and mineralization using a castrated male lamb model. At birth, 40 male lambs were castrated and within 14 days of birth (day = 0) they were assigned (n = 10 per group) to age-matched control lambs (C-AGE) or to receive a 12.5-mg zeranol implant as follows: E-0, implanted on days 0, 45, 90, and 135; E-90, implanted on days 90 and 135; and E-0, 90, implanted on days 0, 90, and 135. Lambs were studied for 163 days. Serum was collected on days 28, 73, 118, 135, and 163 and analyzed for minerals (Ca, P, and Mg), markers of bone remodeling (bone alkaline phosphatase [ALP] and tartrate resistant acid phosphatase [TRAP]), 1,25-dihydroxyvitamin D [1,25(OH)2D], growth hormone (GH), and insulin-like growth factor I (IGF-I). Whole-body bone mineral content (BMC), bone mineral density (BMD), fat mass, and lean mass were determined by dual energy X-ray absorptiometry (DEXA) on days 28, 73, 118, and 163. There was a linear increase in growth at all time points. Whole-body BMC, weight, and lean mass of C-AGE and E-90 lambs were less than E-0, and E-0, 90 lambs at all time points. Whole-body BMD of C-AGE and E-90 lambs was less than E-0 and E-0, 90 lambs at 28 days and 73 days; however, after implantation at day 90 whole-body BMD of E-90 lambs was similar to E-0 and E-0, 90 lambs at day 118 and day 163 and all three were greater than C-AGE lambs. There was no effect of treatment on calcium absorption, serum minerals, hormones, or markers of bone remodeling. We conclude from these data that treatment of growing castrated lambs with an estrogen agonist from birth augments growth, whereas delaying estrogen agonist treatment does not facilitate growth but appears to augment bone mineral accretion. We suggest these observations may have clinical relevance, and deserve consideration when treating children with delays in growth and bone mineral accretion.

Animals↗
PubMed2004

L-prostaglandin D synthase expression and regulation in mouse testis and epididymis during sexual maturation and testosterone treatment after castration.

Lipocalin-type prostaglandin D synthase (L-PGDS) is highly expressed in the adult testis and epididymis of many mammals. The present study was to investigate L-PGDS expression in mouse testis and epididymis during sexual maturation, and the effects of testosterone replacement on L-PGDS expression in epididymis by in situ hybridization and immunohistochemistry. Both L-PGDS mRNA and protein were highly expressed in the interstitial tissue of adult testis. L-PGDS mRNA was first detected on d 30 after birth and exhibited an abundant signal in adult caput and cauda epididymis. L-PGDS immunostaining was first observed on d 30 after birth. There was a strong level of L-PGDS immunostaining in adult epididymis. Castrated male mice were treated with either vehicle or testosterone propionate following 3 d postcastration. L-PGDS expression steadily declined in a time-dependent fashion in control groups. No L-PGDS mRNA expression or immunostaining was detected in the controls for 12 d. When the castrated mice were treated with testosterone propionate for 5 or 12 d, L-PGDS expression was significantly increased in the whole epididymis. These data suggest that L-PGDS expression in mouse epididymis gradually declined in parallel to the declining concentration of endogenous androgen after castration and increased with the treatment of exogenous testosterone, indicating that L-PGDS expression in mouse epididymis was modulated by androgen levels. However, differential expression in different areas of the epididymis may also be influenced by factors derived from the testis.

Animals↗
PubMed1985

Modulation of luteinizing hormone(LH) release by clonidine and opioid peptides in castrated male rats.

The effect of clonidine, a central alpha-adrenergic agonist, on the suppression of LH release induced by beta-endorphin or FK33-824, an endogenous opioid peptide or its synthetic analog, was investigated in castrated male rats, with or without pretreatment with reserpine. Pulsatile LH secretion was inhibited by intravenous injection of FK33-824 (400 micrograms/kg), or intraventricular injection of beta-endorphin (5 micrograms). Without pretreatment with reserpine, intraperitoneal administration of clonidine (1 mg/kg) failed to reverse the inhibition of LH release induced by these peptides. However, with pretreatment with reserpine (10 mg/kg), clonidine abolished the inhibitory effect on LH secretion induced by these peptides in castrated male rats. These data indicate that, unlike the results in ovariectomized, steroid-primed rats, pretreatment with reserpine allows the alpha-adrenergic system to act more peripherally than the opioid neuronal system in a neuronal network-regulating LH release in castrated male rats.

Animals↗
PubMed1986

Effect of prostaglandin D2 on the release of luteinizing hormone and prolactin in castrated and intact male rats.

One, 5 or 20 micrograms of prostaglandin D2 (PGD2) was infused into a lateral ventricle of the brain of anaesthetized intact or castrated male rats, and the response of luteinizing hormone (LH) and prolactin (Prl) was determined. PGD2 stimulated the release of LH in both groups of rats. The greatest LH-response was observed in the castrated rats, where the lowest dose of PGD2 (1 microgram) caused the greatest LH response. This dose was ineffective in the non-castrated animals. PGD2 had no effect on the release of Prl neither in intact nor in orchidectomized rats. It is concluded that PGD2 is capable of stimulating the release of LH in male rats and that the stimulating effect is intensified by removal of the gonadal negative feedback effect on the hypothalamo-pituitary unit.

Animals↗
PubMed2004

[Blood profile of hypothyroid castrated or intact adult female rats].

The relationship between thyroid-gonads on the blood profile was investigated in adult Wistar female rats. These animals were either castrated or intact and were kept under hypothyroidism, induced by daily administration of propylthiouracil (PTU) during 120 days. Two groups (castrated and intact) were kept in an euthyroid condition and used as controls. It was collected plasma for free T4 dosage and blood for hematological analysis. The significant low values of free T4 in the treated rats confirmed their hypothyroid state. The hypothyroidism caused anemia in the rats with functional gonads. The castration reverted the effects of thyroxine deficit in the erythrogram. Both the hypothyroidism and the hypogonadism showed just a discret effect on the leucogram.

Animals↗
PubMed2002

Surgical castration and the effect on aggression in rock hyrax (Procavia capensis).

Lincoln Park Zoo acquired five intact, male rock hyraxes (Procavia capensis) from three separate institutions to exhibit as a group. The animals were of varying ages at the time of acquisition. During quarantine, all five were surgically castrated via a midline laparotomy technique in an attempt to reduce expected aggression within the group. Recommendations for successful castration, based on these five procedures, include performing the procedure on sexually immature hyraxes or sexually inactive adults, the use of a second surgeon during the procedure, and the use of stainless steel surgical clips for ligation of vessels and spermatic cord. Although combinations of the castrated animals coexisted for longer periods than those documented for other nonrelated male groups, aggression was significant and resulted in the death of one individual. Ultimately, all animals were housed individually.

Aggression↗
PubMed1998

Identification of genes expressed in the rat prostate that are modulated differently by castration and Finasteride treatment.

In mammals, testosterone and 5alpha-dihydrotestosterone (DHT) are the principal male hormones (androgens). Testosterone is the most abundant circulating androgen, and is converted in specific tissues to DHT by the 5alpha-reductase enzymes. Although each of these androgens binds to the same receptor protein (androgen receptor, AR), each exerts biologically distinct effects. Theories to explain the specific effects of testosterone and DHT have centered on kinetic differences of binding of androgens to the receptor or differences in the metabolic fates of the two hormones. In the current experiments, differential display PCR (ddPCR) was used to identify genes regulated differently by testosterone and DHT. Adult male rats were treated as follows: castrated, treated with Finasteride (an inhibitor of 5alpha-reductase) or left intact for ten days. RNA was prepared from the dissected prostates of these animals and used for ddPCR. Genes exhibiting four distinct patterns of regulation were observed among the mRNAs. Class 1 genes showed equivalent expression in intact and Finasteride-treated animals, but were absent in castrated animals (mRNAs D1, D2, D6, D10). Class 2 genes showed higher expression in intact animals, intermediate levels following Finasteride treatment, but were absent in castrated animals (mRNA D8). Two classes of gene were particularly intriguing: class 3 showed gene expression only in the intact animal (mRNA D7, D9) and class 4 showed increased gene expression following Finasteride treatment (mRNA D3). While the patterns observed for some of these genes (e.g. D8) suggest that the different biological effects of testosterone and DHT may be due to the lower affinity of the AR for testosterone and limiting tissue concentrations of androgen, our results also suggest that some genes expressed in the rat prostate may be regulated in fundamentally different ways in response to testosterone and DHT.

5-alpha Reductase Inhibitors↗
PubMed1987

Endocrine profiles, testicular gonadotropin receptors and sperm production in hemi-castrated ram lambs.

The effects of hemi-castration upon compensatory hypertrophy, serum gonadotropin and testosterone concentrations, testicular gonadotropin receptors and daily sperm production (DSP) were studied in 10 crossbred ram lambs. At 4 mo of age lambs were either hemi-castrated (HC; n = 5) or left intact (INT; n = 5). Blood samples were collected every 2 h for the first 24 h post-surgery, every 6 h for the next 24 h and then three times weekly for the following 14 wk. Serial blood samples (15-min intervals for 8 h) were collected during the 4th, 8th and 12th week following hemi-castration. Individual mean testicular and epididymal weights increased (P less than .05) 48 and 33% in HC compared with INT rams, respectively. Serum follicle stimulating hormone (FSH) increased (P less than .05) within 8 h after HC, reached peak concentrations within 1 wk and remained elevated for 4 wk before returning to concentrations of INT rams. Neither mean serum luteinizing hormone (LH) nor pulse patterns of LH or FSH were different (P greater than .05) between these two groups at any period examined. Serum testosterone (T) concentrations were lower (P less than .05) during the first 48 h post-surgery in HC rams, but by 1 wk concentrations were similar (P greater than .05) to those in INT rams. Remaining testes from HC and INT rams were removed at 7 mo of age, 3 mo after initial gonadal manipulation. On a per-testis basis there were more (P less than .05) LH and FSH receptors in HC than INT rams, respectively; however, concentrations of receptors were not different (P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Growth and sexual characteristics of suckling beef calves as influenced by age at castration and growth implants.

A 2-yr study using crossbred male calves (n = 228) evaluated castrating at birth or at 4 mo of age and use of anabolic growth implants (none, zeranol or estradiol-17 beta). Angus, Hereford and Brahman crossbred calves produced in seven cow-calf units that varied by breed component, stocking rate and calving season were allotted to treatment at birth in a 2 x 3 factorial arrangement. Growth implants decreased (P less than .01) testicular weight and expression (P less than .05) of male secondary sex characteristics in suckling bull calves at 4 mo. Implanted calves were shorter (P less than .05) at the hips and had shorter front legs (P less than .01) at both 4 mo and at weaning. Cannon bone circumference at weaning was increased (P less than .05) by growth implants. Age at castration did not affect (P greater than .05) calf performance or body characteristics. Calves given growth implants had higher (P less than .05) rates of gain from birth to 4 mo than did nonimplanted calves (.75 vs .71 kg/d). Implanted calves were heavier (P less than .01) at weaning and had higher (P less than .01) ADG from 4 mo to weaning than did nonimplanted calves. These data indicate no benefit from delaying age at castration, but implanting increased weaning weight an average of 8.2 kg.

Age Factors↗
PubMed2006

The complex blood supply to the equine testis as a cause of failure in laparoscopic castration.

REASONS FOR PERFORMING STUDY: Intra-abdominal ligation/ transection of the spermatic cord may result in necrosis of the testis; castration of abdominal cryptorchids via laparoscopy has therefore become common. Notwithstanding some adaptations of the technique, a small percentage of operations fail, prompting research into the anatomical background and clinical relevance of the procedure. HYPOTHESIS: That an alternate blood supply may prevent complete necrosis of the testis after spermatic cord transection. OBJECTIVE: To establish the prevalence of the problem in normal and cryptorchid stallions. METHODS: In a preliminary study, the spermatic cords of 8 normal stallions were ligated and transected at different sites and in various manners. Five weeks later the testes were removed and the vitality of both the testes and epididymes was evaluated. In a prospective clinical trial, intra-abdominal spermatic cord transection was performed in 241 cryptorchid and normal stallions. In cases of surgical failure, the testes were removed and histology performed. RESULTS: Examination of the specimen removed from the 8 animals of the preliminary study revealed that all epididymes were completely or largely spared. All except one testis were completely necrotic. In the patients that underwent surgery all abdominally retained testes (n = 123) were necrotic, while 5 out of 88 inguinally retained and 8 out of 236 normally descended testes had partially survived. The pattern of survival differed between inguinally retained and normally descended testes. The epididymes of these 13 horses were (largely) vital. The (partial) survival of the epididymes and inguinally retained testes was ascribed to an alternate blood supply via anastomosing vessels derived from the cremasteric artery. A tributary from the external pudendal artery was considered responsible for the partial survival of normally descended testes. CONCLUSIONS AND POTENTIAL RELEVANCE: After intra-abdominal transection of the entire spermatic cord, 5.6% of inguinally retained and 3.4% of normally descended testes failed to become completely necrotic, as a result of an alternate blood supply via the cremasteric and/or external pudendal artery. Therefore, laparoscopic castration without orchidectomy cannot be recommended as a trustworthy method for castration of inguinal cryptorchids and normal stallions.

Animals↗
PubMed1997

The expression of receptors for estrogen and epithelial growth factor in the male rabbit prostate and prostatic urethra following castration.

In the lower urinary tract of the male rabbit, estrogen receptors (ERs) are restricted to the urethra and the prostatic stroma. At present, the function of ERs in these tissues is not known. Epithelial growth factor (EGF) stimulates proliferation of epidermal and epithelial tissues, and several animal studies have indicated that EGF is regulated by estrogen. On this background, we have studied the effect of castration on the expression of ERs and EGF receptors in the rabbit prostatic urethra and prostate. Twelve male rabbits were studied fourteen days after castration, and eight normal rabbits were included as controls. In the control group, ERs were found in the urothelial lining and lamina propria of the prostatic urethra, and in the prostatic stroma. EGF receptors were demonstrated in the epithelial lining of the prostatic urethra and the glandular epithelium of the prostate. Following castration, the expression of ERs, assessed as the increase in the number of positively stained specimens, increased significantly in the lamina propria of the prostatic urethra and the prostatic stroma. EGF receptor expression increased significantly in the epithelial lining of the prostatic urethra. In the prostate, the increase was not significant. The results give no support to the view that ERs play role in the regulation of EGF receptors in the rabbit prostatic urethra nor the prostate.

Animals↗
PubMed1989

Effects of a restricted diet on the submaxillary gland of intact and castrated male rats.

Effects of diet restriction (50% of normal) during 4 weeks were studied in intact (controls) and castrated rats. A restricted diet led to cessation of animal growth. No differences were observed between controls and castrated rats. However, underfeeding produced a reduction of testicular weight in intact rats. Histochemical observations showed a reduction of tryptophan (a marker of the presence of testosterone-dependent protein) in the submaxillary gland from animals fed a restricted-diet. In animals fed a normal diet, castration reduced significantly the gland weight, as well as the diameter of tubules and acini. When animals fed a restricted-diet are compared, no significant differences were found in the diameter of tubules and acini or in the weight of submaxillary glands.

Animals↗
PubMed1988

Proliferation of skeletal muscle satellite cells after castration and administration of testosterone propionate.

Thirty-six neonatal pigs were randomly assigned to the following treatment groups: sham implanted gonadally intact males (B), sham-implanted castrated males (C), or castrated males implanted with testosterone propionate (C + TP). Four pigs from each group were sacrificed at 7, 14, or 21 days of age after a 6-hr continuous infusion of [3H]thymidine. Myofibers isolated from the triceps brachii were prepared for satellite cell enumeration by light microscope autoradiography. A developmental decline in labeled myofiber nuclei occurred in all groups, however, the greatest decline occurred in C (P less than 0.01). A treatment-by-age interaction was observed for percentage of labeled nuclei. Castration reduced total and labeled nuclei per millimeter myofiber (P less than 0.05), and C + TP had a higher percentage of labeled nuclei than C (2.8 vs 2.2%; P less than 0.05). Since triceps brachii muscles from 21 day B and C + TP were 120% (P less than 0.05) of C, the results indicate that postnatal growth of skeletal muscle is dependent on satellite cell mitotic activity and that testosterone enhances this activity in neonatal pigs.

Animals↗
PubMed2004

Parasitic castration of Eurhomalea lenticularis (Bivalvia: Veneridae) by a digenetic trematode: quantitative histological analysis.

The clam Eurhomalea lenticularis may be parasitized by digenean trematodes of the family Plagiorchidae, specifically in the gonads (parasitic castration). A quantitative histological analysis of the parasitized gonads demonstrated a significant decrease in gonadal area, in the size of individual acini, and in the numbers of differentiated germ cells compared to unparasitized clams. Castration may be caused by mechanical compression due to trematode sporocyst growth. However, the uniform loss of germ cells in areas without sporocysts suggests that a more generalized mechanism is responsible. We suggest that parasitic castration has a primary effect on the host's neuroendocrine and gametogenic systems that regulate gamete production.

Animals↗
PubMed1989

[Testicular endocrine function in patients with prostatic cancer receiving medical castration by long-term administration of LH-RH agonists].

Six patients with advanced prostatic cancer who had been treated by long-term administration of LH-RH agonistic preparations (Buserelin or Leupron) were tested for their pituitary-testicular endocrine functions. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), prolactin (PRL), estradiol (E2) and dihydrotestosterone (DHT) were measured consecutively. In all medically castrated patients, serum levels of LH, FSH, T, DHT and E2 were suppressed and particularly serum T levels were below the castration level of 1.0 ng/ml. On the other hand, serum PRL levels were unchanged after the long-term treatment with the agonists. Serum LH and FSH levels failed to respond to LH-RH stimulation after the treatment, whereas serum T responded to stimulation by human chorionic gonadotropin (hCG) to various degrees. It was remarkable that, in 4 out of 6 medically castrated patients treated up to more than 3 years, serum T response levels above 1.0 ng/ml were noted. It is suggested that testicular endocrine function to secrete T and DHT in patients under treatment with long-term LH-RH agonist administration are still preserved in response to hCG stimulation.

Adenocarcinoma↗
PubMed1999

Use of cyproheptadine to control urine spraying in a castrated male domestic cat.

A 10-year-old castrated male domestic cat was admitted to the hospital because of lifelong urine spraying of vertical surfaces. A diagnosis of territorial urine marking was made. Laboratory analytes for urine analysis, hemogram, serum biochemical analysis, and serum thyroxine concentration were within reference ranges, and testosterone concentration was consistent with the reference range of castrated male cats. Treatment included behavior modification and the administration of cyproheptadine, which resulted in the immediate arrest of undesirable urine marking. Cyproheptadine administration was adjusted to determine the lowest dosage that effectively maintained the cat's consistent use of the litter box. Cyproheptadine administration was recommended for at least 1 year before any attempt to withdraw its use. A follow-up phone call to the owner 8 months after the beginning of treatment revealed that the cat continued to have remission of inappropriate urination. Cyproheptadine, an antihistamine prescribed for its orexigenic effects in cats, has antiandrogenic effects in other species. Information in this report indicates that cyproheptadine is effective in the control of urine spraying even in castrated cats.

Animals↗