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PubMed1999

Effects of castration and testosterone replacement on veno-occlusion during penile erection in the rat.

AIM: To determine if androgens directly regulate veno-occlusion or if androgens act indirectly to maintain the penile structures which control outflow. METHODS: Using CASTRATE and TESTO rats, measurement was made of mean arterial pressure (MAP), intracavernosal pressure (CCP), and intracavernosal flow (CCF) during erection resulting from stimulation of the autonomic innervation of the penis. CCP and CCF were also measured during saline infusion into the cavernosal sinuses before and after treatment with sodium nitroprusside (SNP, a nitric oxide donor drug) to fully relax cavernosal smooth muscle. Penile tissue was also collected to measure the content of alpha actin and proline and hydroxyproline to determine if brief withdrawal of androgenic support led to changes in the number of smooth muscle cells or the collagen content of the tissue. RESULTS: Infusion of saline into the cavernosal sinuses demonstrated that veno-occlusion was defective in CASTRATE rats while veno-occlusion was fully functional in TESTO animals. Furthermore, veno-occlusion could be induced in CASTRATE rats if they were first treated with SNP. This observation suggests that failure of veno-occlusion in the CASTRATE rats is due to a deficiency in the production of NO resulting in a reduction in the degree of relaxation of the penile smooth muscle. The measurements of smooth muscle a actin and proline and hydroxyproline content of collagen showed that both were unaffected by castration and that the basic structure of the penis did not degenerate after one week without androgenic support. CONCLUSION: These results can be interpreted to mean that androgens control the veno-occlusive mechanism indirectly via a NO dependent mechanism and not by maintaining the structures of the penis which are essential to veno-occlusion.

Animals↗

PubMed2001

Urinary excretion of calcitonin gene-related peptide in males with hot flushes after castration for carcinoma of the prostate.

OBJECTIVE: The majority of men who undergo surgical or medical castration due to prostatic carcinoma develop vasomotor symptoms with hot flushes. The mechanisms behind these symptoms are poorly understood. One possible explanation is a release of the vasodilatory peptide calcitonin gene-related peptide (CGRP) from perivascular nerves, which seem to be involved in the mechanisms behind vasomotion and sweating in postmenopausal women. The aim of this report was to investigate whether CGRP is involved in vasomotion in men after castration therapy. MATERIAL AND METHODS: Twenty-four hour urine excretion of CGRP was analysed in 15 men with prostatic carcinoma, using radioimmunoassay before and 3 months after surgical or medical castration. RESULTS: Eleven of the 15 men developed hot flushes during the observation period of 3 months. Twenty-four hour urine excretion of CGRP did not change significantly after castration, either in the group as a whole or in those 11 men who developed hot flushes. CONCLUSIONS: Even though we did not observe any significant changes in 24-h urine excretion of the potent vasodilator CGRP after castration it is possible that serum levels of CGRP increase during hot flushes, without having an effect on the 24-h urine excretion of the peptide.

Aged↗

PubMed1992

Coordinate loss of growth regulatory factors following castration of rats carrying the Dunning R3327 G prostatic tumor.

Hormonal manipulation of prostate cancer is an effective therapy for metastatic disease. Unfortunately, following an initial response tumors reestablish themselves as hormone independent variants and progress. This study was designed to assess the interrelationship of cytokeratin P (Cyto P), vimentin, epidermal growth factor receptor (rEGF) and tissue testosterone following androgen deprivation therapy. Animals bearing the hormone dependent Dunning R3327 G subline prostatic adenocarcinoma were surgically castrated and progressing tumors from both hormone intact and castrated groups were quantitatively assayed for immunohistologic reactivity against the described markers. The results demonstrate a significant (p < 0.05) decrease in cytokeratin (Cyto P), rEGF and testosterone levels following castration. When the expression of both rEGF and Cyto P are related to the tissue testosterone content, it is observed that the ratio between rEGF and testosterone remains essentially unchanged (0.65 +/- 0.21 to 0.65 +/- 0.41), suggesting that in the Dunning R3327 G subline, rEGF expression is coordinately under androgen control. At least some cytokeratin expression also appears to be particularly sensitive to androgen levels, since the ratio between Cyto P and testosterone decreased from 0.92 +/- 0.39 to 0.35 +/- 0.41 following castration. In contrast, following castration, the expression of vimentin was unaffected.

Adenocarcinoma↗

PubMed2003

[Establishment of prostatic hyperplasia model with castration beagle canines].

OBJECTIVE: To establish a prostatic hyperplasia model with Beagle canines. METHODS: Twenty-four two-year-old male Beagle canines were divided into treatment and control groups at random and were administrated testosterone propionate (TP) through intramuscular injection two months after castration. Three treatment groups were given 0.8, 2.5 and 7.5 mg/kg TP respectively, and the control was given the same volume of vehicle. Two months later, half of the animals were killed and the serum and prostate were prepared. After the wet weight and volume of prostate were measured, the dihydrotestosterone (DHT) level of serum and prostate were detected with DHT radioimmunoassay (RIA) kit, and paraffine section from canine prostate was stained by the HE methods. Pictures were taken by digital camera under microscope, and all the pictures were analyzed by computer for epithelial cell height and acinar luminal area of prostate with micro image analysis software. The canine prostate volume was measured with ultrasonic diagnosis instrument before castration, at two months after castration and at two months after being given TP. RESULTS: The ultrasonic results showed that the prostate volumes of all the canines were smaller at two months after castration than before castration (P < 0.05), and after having been administrated TP for two months, and the prostate volumes of all treatment groups were larger than those of the control group (P < 0.01). The wet weight of the prostate of the treatment group was higher than that of the control group (P < 0.05), and both had dose-dependent relationship. The DHT level of serum and prostate of the canines became higher with the increase of TP dose. The results of micro image analysis showed that the acinar luminal area of prostate was enlarged, and the epithelial cell height increased with larger dose of TP. CONCLUSIONS: It is practicable to establish prostatic hyperplasia model in Beagle canines after two months of TP administration.

Animals↗

PubMed1987

[Effect of neonatal castration on sex steroid receptor levels in the hypophysis of male rats].

The content of estradiol and testosterone cytosolic and nuclear receptors has been studied in the pituitary body of adult male rats gonadectomized on day 1-3 after birth (long-term castrates) or in adulthood (short-term castrates). Intact male rats and long- and short-term castrates had the same level of cytosolic and nuclear estrogen receptors. The number of cytoplasmic and nuclear testosterone-binding sites was identical in the pituitary body of adult intact mice and long-term castrates. Contrastingly, the concentrations of androgen cytosolic and nuclear receptors were significantly lower in neonatally castrated males compared to intact adult animals. The results obtained indicate that nuclear testosterone receptors in the pituitary body mediate negative feedback effect of androgen on the release of luteinizing hormone and that the formation of thin mechanism occurs within the first days of life.

Animals↗

PubMed1985

Presence of C-19 steroids in mammary Shionogi carcinoma (SC 115) in castrated mice.

Intact and castrated male DD/S mice were inoculated with androgen-dependent cells (SC 115). All intact animals developed tumors after Day 12 of inoculation; however, six of seven castrated animals presented tumors 48 days postinoculation. The levels of steroids in both tumors were then examined. In castrated mice, dehydroepiandrosterone and androst-5-ene-3 beta, 17 beta-diol levels were diminished by 30% and 70%, respectively, while the amounts of testosterone and androstenedione were reduced by more than 90%. Our data also demonstrate that androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol were decreased to 60% and dihydrotestosterone decreased to 6% of their normal value, respectively. This latter level (0.48 nM) was sufficient to still effect a potent androgenic response in the tumor. Besides, a highly significant correlation was found in these tumors between various C-19 steroids (dehydroepiandrosterone and androstane-3 alpha, 17 beta-diol, r = 0.97, P less than 0.01), suggesting a possible conversion of C-19 precursors into potent androgens in the tumors. Determination of the plasma steroid levels in the castrated animals clearly confirmed that potent androgenic steroids and precursors were still in the circulation 3 days after castration. It thus appears that C-19 steroids from adrenal origin may be also involved in "independent" tumor growth.

Animals↗

PubMed1993

Temporal relationships of statin and terminin expression in ventral lobe of rat prostate following castration.

The purpose of this study was to determine the temporal relationships, in the rat prostate following castration, the expressions of terminin, a cytoplasmic marker for senescence, and, statin, a nuclear marker for cell quiescence and senescence. The presence of these two proteins was determined at 0, 1, 2, 4, 8, 24 and 48 hours in the ventral lobe of the prostate following castration. Immunofluorescence techniques for double labelling were used and assessed with confocal microscopy. At 0 hour the mean % labelling index (LI) for terminin was 0% and 98% for statin. One hour following castration a complete reversal of expression of these two markers occurred indicating that the terminin marker is expressed at the start of programmed cell death or apoptosis. The mean % LI for terminin at 1, 2, 4, 8, 24 and 48 hours following castration were 54, 82, 63, 39, 44 and 41% respectively. The mean % labelling index of statin remained at zero during these time intervals. It is concluded that following castration, the prostatic ventral lobe exits from the quiescent phase to reenter cell cycle traverse. This is coupled by the loss of statin and the expression of the cytoplasmic marker terminin at the start of programmed cell death prior to the appearance of any histologic features of apoptosis.

Animals↗

PubMed1995

Enhanced production of B lymphocytes after castration.

Castration has long been recognized to stimulate thymic growth and augment cellular immunity. We sought to determine whether castration affects B lymphopoiesis by analyzing the phenotype of bone marrow and spleen cells from animals postcastration. In this report, we show that the bone marrow cells from castrated male mice show a sustained, twofold to threefold increase in numbers of B220+/IgM- cells and of newly formed B220+/IgM+ B cells. Most of the expanded B220+/IgM- cell population consisted of small, HSAhi, CD43- cells characteristic of pre-B cells. The castrated animals also showed increased numbers of splenic B cells, primarily consisting of small IgM+, IgDlo, B220lo, HSAhi cells. Taken together, these results show that castration causes dramatic, long-lived enhancement of B lymphopoiesis in bone marrow and increased numbers of mature B cells in the periphery.

Animals↗

PubMed1995

Castration alters peripheral immune function in normal male mice.

While it is generally recognized that females show enhanced cell-mediated and antibody responses to antigenic stimulation, the physiological basis for this observed sexual dimorphism of the immune response is not well understood. We report here studies on the effects of androgen deficiency on the peripheral immune system. Intact male mice were compared to animals castrated 3-4 months previously. Phenotypic characterization of thymocyte and lymphocyte subpopulations was carried out using dual-colour flow cytometry. In vitro production by spleen cells of interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma), and levels of total immunoglobulin and autoreactive antibodies was measured by specific immunoassays. In addition to thymic hypertrophy, castrated animals showed significant splenic enlargement, which was largely owing to expansion of the B-cell population. The castrated spleens contained relatively fewer mature T cells than intact controls (P < or = 0.001), but culture supernatants from these spleen cells contained higher levels of IL-2 and IFN-gamma than control cultures (P < 0.04). Levels of in vitro antibody synthesis (IgM, IgG, IgA) were not higher in castrated animals compared to controls, but the castrate spleen cell cultures showed increased levels of production of two autoreactive antibodies, anti-IgG (rheumatoid factor) and anti-thyroglobulin. These data suggest that androgen deprivation results in a relative decrease in the number of mature peripheral T cells, but those which reach the spleen have functional characteristics suggestive of enhanced activation. Dysregulation in the B-cell compartment may be the result of altered effects of T-cell-mediated control.

Androgens↗

PubMed1994

Impact of prolactin on epididymal lipid profile in castrated rats.

Prolactin treatment to castrated rats led to accumulation of triacylglycerol and esterified cholesterol. There was no appreciable drift in epididymal cholesterol: phospholipid ratio between the prolactin treated and control animals. However, further analysis of phospholipids showed a build up of phosphatidyl inositol, phosphatidyl choline and phosphatidyl ethanolamine but a drop in the levels of phosphatidyl serine and sphingomyelin in prolactin treated castrated rats as compared to those castrated animals injected with vehicle alone. Changes in phospholipids reported above were prominently seen in the group of castrated rats that received 100 micrograms oPRL/100 g body weight but not in those animals which received either lower or higher doses of the hormone. Interestingly, bromocryptine treatment in castrated rats produced a general depletion in the levels of all lipid classes studied in the epididymis. It is suggested that this may be due to impaired synthesis and/or increased breakdown of lipids in this organ.

Animals↗

PubMed1994

[Piglet castration--pain sensation and pain elimination].

Electroencephalographic (EEG) recordings performed in piglets during Trapanal anaesthesia showed distinct changes in bioelectrical brain activity in some piglets when castration was carried out. Only an additional extradural anaesthesia seemed to interrupt the transmission of peripheral pain stimuli to the central nervous system. Based on the protocol used EEG did not reveal a marked response to noxious stimulation. Castration of piglets up to two weeks of age were performed during general anaesthesia with Trapanal or Disoprivan or local anaesthesia with Hostacain or without any anaesthesia. The different modes of anaesthesia have had no effects to postoperative wound healing and weight gain between groups as well as between males and females within single groups. With regard to insufficient analgesia and/or partially extreme secondary effects the application of investigated anaesthetic methods on the occasion of castration of piglets is not justifiable at present. Castration in piglets up to an age of two month without anaesthesia is allowed by the animal protection law. However, due to improved wound healing and decreased response to surgical stimulus we suggest to perform castration during the first 10 days after delivery.

Anesthesia↗

PubMed1996

Comparison of two techniques for castration of llamas.

OBJECTIVE: To compare a prescrotal castration technique with the conventional bilateral scrotal incision technique for castration of llamas. DESIGN: Prospective randomized controlled trial. ANIMALS: 10 clinically normal, sexually intact male llamas. PROCEDURE: Five llamas were castrated by use of a 5-cm skin incision located 2 to 3 cm lateral to the ventral midline and approximately 15 cm cranial to the scrotum, which was closed with absorbable suture material to allow primary healing. Five other llamas were castrated via a more conventional technique, with a 5-cm scrotal incision positioned directly over each testis, which was allowed to heal by second intention. RESULTS: The prescrotal technique required significantly more time to complete; however, no additional anesthesia was required to complete the longer procedure. Llamas castrated with the prescrotal technique required less aftercare and had less incisional pain when the area was palpated. CLINICAL IMPLICATIONS: Both techniques are safe and effective. Some clients, however, find the prescrotal technique more aesthetically acceptable. The prescrotal technique may be more clinically important where fly control is difficult.

Animals↗

PubMed1997

Longitudinal and cross-sectional studies to evaluate the risk of sarcoid associated with castration.

In order to investigate whether gender and castration have an effect on the time to the development of sarcoids, a retrospective study in a population of donkeys was conducted using survival analysis techniques. Univariable Kaplan Meier product limit curves identified males as having significantly lower survival probability, or higher risk of developing sarcoids, than females (P < 0.01). Cox's proportional hazard model was used to assess the effect of age at entry to the population whilst simultaneously considering the effect of gender on the hazard of developing sarcoids. Age at entry and gender were both significantly associated with the hazard of sarcoid (P < 0.01). Animals younger at entry were at increased risk of being diagnosed with sarcoids and the hazard ratio for being male was 1.9. Although male animals castrated after entering the population had significantly poorer survival rates than those castrated prior to entry, this effect was not significant when age at entry to the population was fitted to the model, demonstrating that the castration procedure within the population per se was not a risk factor. Although there was a trend toward stallions being at increased risk when compared to geldings, the effect was not statistically significant, particularly when controlling for age. It was concluded that a multicentre study or meta-analysis will be necessary to resolve the issue of risk associated with castration.

Aging↗

PubMed1998

[Comparison of two castration methods in cattle: plasma cortisol levels, leukocyte count and behavioral changes].

Two methods of castration (surgical and Burdizzo method) of male calves were compared by measuring plasma cortisol concentrations. Increased plasma cortisol values were found only during the first three hours after castration. There were no significant differences in plasma cortisol values and changes of behaviour between groups of surgical and Burdizzo castrated calves. Plasma cortisol values did not decrease during the first days after castration. The results suggest, that surgical and Burdizzo-castration do not differ in regard to pain.

Animals↗

PubMed2026

Real-World Outcomes of Olaparib in Japanese Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer: Exploratory Analysis of BRCA2 Loss and Microsatellite Instability Status.

OBJECTIVES: Metastatic castration-resistant prostate cancer has a poor prognosis. Although olaparib has demonstrated efficacy in patients with BRCA1/2 mutations, real-world data in Japanese patients remain limited. We aimed to evaluate the efficacy and safety of olaparib in patients with BRCA-mutated metastatic castration-resistant prostate cancer and explore the association of BRCA2 loss and microsatellite instability status with treatment outcomes. METHODS: We conducted a multicenter retrospective study of 34 patients with BRCA-mutated metastatic castration-resistant prostate cancer treated with olaparib between December 2020 and December 2024. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, prostate-specific antigen-50 response rate, and safety. Exploratory analyses were performed. RESULTS: Among the 34 patients, 33 had a BRCA2 mutation and one had a BRCA1 mutation. Prostate-specific antigen reduction was observed in 76.4% of patients; prostate-specific antigen-50 response rate was 58.8%. Median progression-free and overall survival were 15.8 and 35.1 months, respectively. Grade ≥ 3 adverse events (most commonly anemia) occurred in 17.6% of patients. Treatment discontinuation due to adverse events occurred in one patient. Exploratory analyses were performed in 23 BRCA2-mutated patients who underwent comprehensive genomic profiling. BRCA2 loss was observed in 39.1% of patients and showed a trend toward prolonged progression-free survival, whereas microsatellite instability-high status was observed in 13.0% and was associated with shorter progression-free survival. CONCLUSIONS: Olaparib demonstrated efficacy and safety in Japanese patients with BRCA-mutated metastatic castration-resistant prostate cancer. Exploratory analyses revealed that BRCA2 loss may be associated with prolonged progression-free survival, whereas microsatellite instability-high status may be associated with shorter progression-free survival. These findings require validation in larger cohorts.

Humans↗

PubMed1975

Quantitative morphology and carbohydrate histochemistry of the mouse submandibular gland following prepubertal castration.

The endocrinologic basis for morphological and biochemical sex differences in the mouse submandibular gland have not been clarified. Previous studies have emphasized the maintenance of glandular differences in adult animals, rather than considering the factors responsible for their developmental etiology. Male CD-1 mice were castrated at intervals between 10 and 50 days of age and killed at 100 days. The quantitative development of granular tubules and the carbohydrate histochemistry of the submandibular glands were compared to untreated males and females. The area of granular tubules increased with age at castration. Nested analysis of variance indicated significant differences among treatments and among sections within individual glands. No group of castrated males had a greater development of tubules than untreated females. Carbohydrate histochemistry demonstrated an increase in carboxylated mucosubstances in the acinar cells and granular tubule cells of castrated animals.

Age Factors↗

PubMed1978

Synergistic effects of prolactin and testosterone in the restoration of rat prostatic epithelium following castration.

Prolactin is known to enhance the uptake and metabolism of testosterone in male accessory sex organs and to increase the weight of accessory sex organs from castrated rats over those from controls treated with testosterone alone. The present study was directed toward defining fine structural changes detectable with scanning and transmission electron microscopy which might accompany such responses. Accordingly, rat ventral prostate gland was examined from castrated animals which had received testosterone propionate and ovine prolactin singly or together, or which had received vehicle only. Unoperated animals served as additional controls. Post-castration glandular atrophy was not influenced by prolactin treatment alone. Testosterone restored epithelial height, secretory product, Golgi complexes and rough endoplasmic reticulum, such that cellular and tissue morphology was generally indistinguishable from that of unoperated controls. Prostatic tissue from animals given testosterone and prolactin simultaneously exhibited pleomorphic, cytoplasmic apical projections which extended into the acinar lumen. Transmission electron microscopy demonstrated that these blebs were devoid of organelles and microvilli; scanning electron microscopy revealed that the blebs were highly wrinkled and more numerous than were the projections observed in tissue from animals treated with testosterone alone, or in tissue from unoperated controls. It is suggested that such blebbing may reflect enhanced apocrine secretion in prolactin/testosterone stimulated restoration of the prostate gland in castrated rats.

Animals↗

PubMed1978

The effects of 5alpha-reduced androgens on maintenance and regeneration of prostate glands and seminal vesicles in castrated and hypophysectomized rats.

The effects of 5alpha-androstane-3alpha, 17beta-diol (3alpha-diol) and 5alpha-androstane-3beta, 17beta-diol (3beta-diol) were studied in rats hypophysectomized and treated daily for 30 days with the steroids, starting on the day of surgery (hypophysectomized, H) or 30 days following the removal of pituitary (hypophysectomized regressed, HR). The ability of 3beta-diol to maintain and restimulate the prostate glands and seminal vesicles of castrated (C) and castrated regressed (CR) rats, respectively, was also studied. This androgen (3beta-diol) was able to maintain as well as rejuvenate to some degree the sexual accessory glands of all treatment groups. The prostate glands and seminal vesicles in both castrated experimental groups showed increased stimulation with progressively higher dosages of 3beta-diol. At all dose levels, stimulation of seminal vesicles of CR rats was comparable to that of non-regressed castrates. The prostate glands, on the other hand, showed better maintenance in the higher dosage group. In H rats, the stimulation of sexual accessory glands by both androgens was not significantly different than normal controls. The seminal vesicles and prostate glands of HR rats treated with 3alpha-diol were well stimulated and comparable to those of H rats treated with 3alpha-diol. The seminal vesicles of HR rats treated with 3beta-diol were also well stimulated, though not to the extent as those with 3alpha-diol treatment. The prostate glands of the 3beta-diol treated HR rats were significantly smaller than those of the 3alpha-diol treatment group. However, these miniature glands were morphologically stimulated as evidenced by mitosis of parenchymal cells and accumulation of secretory products in the alveoli. This study clearly indicates that 3beta-diol is biologically active and the degree of stimulation varies with the animal preparation in which the androgens were tested.

Androstane-3,17-diol↗