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Factors affecting acetohexamide reductase activities in microsomes and cytosol from the kidney of male rats: age and castration.

Acetohexamide reductase activity in microsomes from the kidney of male rats increased markedly at puberty to approach the maximum level at 8 weeks of age; it was not detected until 4 weeks of age. Furthermore, castration suppressed effectively the activity in kidney microsomes at 8 weeks of age. These findings clearly indicate that the activity in kidney microsomes can be regulated by androgens. On the other hand, in cytosol from the kidney of male rats, a higher acetohexamide reductase activity was observed at all weeks of age tested. Castration had no significant effect on the activity in kidney cytosol.

Aging↗

[Effects of osthol on androgen level and nitric oxide synthase activity in castrate rats].

OBJECTIVE: To investigate the effects of osthol on androgen level and nitric oxide synthase (NOS) activity in castrate rats. METHODS: Immature castrate male rats were treated with osthol daily for 20 d. The levels of testosterone(T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in serum and the activity of NOS, the nitric monoxide (NO) level in penis tissue were determined. RESULTS: T( P < 0.05), LH( P < 0.05) and FSH( P < 0.01) were significantly increased at the high dose of osthol treatment. The high and low dose of osthol treatment significantly enhanced the activity of NOS (P < 0.01). CONCLUSION: Osthol could increase androgen, gonadotropin and nitric oxide synthase (NOS) activity. It suggested that osthol had androgen-like effect and gonadotropin-like effect.

Androgens↗

Suppression of chemically-induced liver tumors by castration or estradiol-3-benzoate treatment in F344 rats.

Epidemiological data reveal that the incidence of liver cancer is markedly higher in men than women. To clarify the mechanism responsible for the induction of higher incidence of liver tumors in male animals, we investigated the modifying effect of sex hormones in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. F344 male rats (n=120) were divided into two experiments, experiment I (Exp I) and experiment II (Exp II). In each experiment, 60 rats were randomly allocated into four groups. The mini-osmotic pumps containing doses of 47.5 mg (Exp I) or 23.75 mg (Exp II) of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. Animals in group 2 were castrated one week prior to DEN treatment, and animals in groups 3 and 4 were treated with 1 or 10 microg of estradiol-3-benzoate (EB), respectively, one week prior to DEN treatment. Animals in group 1 were treated with DEN alone and sham-operated at the same time. All animals were sacrificed 26 weeks after DEN treatment. In Exp I, liver tumor incidence of group 3 decreased significantly compared with that of group 1 (p<0.05), and tumor multiplicities of groups 2, 3 and 4 were decreased significantly compared to that of group 1 (p<0.01). In Exp II, tumor incidence of group 3 was significantly different (p<0.05) when compared to that of group 1. Immunohistochemical expression of ERalpha was shown in normal appearing cells, but not in tumor cells. Western blot analysis confirmed that ERalpha expression was higher in normal liver tissue compared to tumor tissues. Taken together, we conclude that castration or EB treatment has an inhibitory effect in DEN-induced hepatocarcinogenesis in F344 rats. The reason for ERalpha loss in tumor cells should be further elucidated.

Animals↗

[Unsuccessful laparoscopic castration in a cryptorchid Frisian stallion].

A 2-year-old unilateral inguinal cryptorchid Frisian stallion was castrated by bilateral laparoscopic intra-abdominal spermatic cord transection. Because blood testosterone levels were still high on postoperative day 7, both testicles were removed using an open approach. Pathology revealed the presence of vital Leydig-cells in both testes. Failure of the laparoscopic castration in this horse was attributed to an alternate blood supply to the testes by vessels derived from the cremaster and/or external pudendal artery.

Animals↗

Clinical and pathologic features of prostatic adenocarcinoma in sexually intact and castrated dogs: 31 cases (1970-1987).

The medical records of 31 dogs diagnosed with prostatic carcinoma at the teaching hospital between January 1970 and October 1987 were reviewed to determine whether gender status had an effect on the clinical features or biologic behavior of the disease. The only significant difference between sexually intact and castrated dogs was increased prevalence of pulmonary metastasis in castrated dogs.

Adenocarcinoma↗

A preliminary study of immunological castration in colts.

This study tested the effectiveness of a conjugated GnRH vaccine for stimulating antibody production, suppressing testosterone secretion and depressing testicular development in yearling colts. Two colts were allocated to each of three groups, (1) control, (2) subcutaneous and (3) intramuscular vaccinations. Two injections of the vaccine were given 11 weeks apart. Liveweight gain was not affected by vaccination but plasma testosterone concentrations in the treated colts were suppressed and their antibody titres to GnRH were greater than 1:1000. Testicular development in the treated colts also was retarded at this time, which was approximately 28 weeks after the first injection. Semen samples, containing spermatozoa, were collected from all the colts prior to their castration at the end of the investigation. Antibody titres and testosterone concentrations in the treated colts had returned to levels similar to those of the controls by the end of the experiment. The testes of the vaccinated colts were still smaller than those of the controls on castration but were, nevertheless, increasing in size. Morphometric analysis of testicular histology and daily sperm production data indicated that the testes of the treated colts were recovering and would probably have regained normal function had they been left in situ.

Animals↗

Influence of pituitary on histology of Bidder's organ in castrated toad Bufo melanostictus.

Weight, number of follicles and corpora lutea of Bidder's organ increased significantly after castration of adult toad in breeding season. Removal of pituitary along with testes decreased both weight and number of follicles and corpora lutea. Administration of luteinizing hormone (LH) in castrated and hypophysectomized toad showed more or less similar result as that of control indicating that LH has an effect on the histology of Bidder's organ in the toad.

Animals↗

Effects of tail docking and castration on behaviour and plasma cortisol concentrations in young lambs.

Behavioural and cortisol responses of lambs to the usual husbandry practices of castration and, or, tail docking using tight rubber rings were investigated between birth and seven days old. There were four treatments: control handling and blood sampling (n = 52), tail-docking (T) (n = 57), castration plus tail-docking (CT) (n = 54) and intravenous adrenocorticotrophin injection (ACTH) (n = 52). After treatment there was a transient rise in plasma cortisol concentration, the magnitude and duration of which increased in the following order; control, T, CT and ACTH. Behavioural characteristics indicative of distress included restlessness (standing up and lying down frequently, rolling, kicking, stamping), lateral recumbency, immobility with neck extension and hyperventilation. Using changes in cortisol concentrations and behaviour the lamb responses were characterised as reflecting 'mild disturbance without distress' (control, ACTH), 'mild distress' (T) and 'marked distress' (CT). The mild distress lasted for about 30 minutes in T lambs and marked distress for about 60 minutes in CT lambs.

Adrenocorticotropic Hormone↗

Effects of castration, androgen replacement and flutamide treatment on the contractile function of the rat prostate.

The contractile activity of the rat prostate was registered in vivo by means of a video recording system. An increase in tone was registered in control animals after electrical stimulations were applied to hypogastric ganglion. Similar result was obtained after norepinephrine or acetylcholine administration. Such responses suffered a progressive declination in bilaterally castrated rats, although marked ultrastructural changes were not seen in the prostatic muscle cells after surgery. However, the rhythmic spontaneous activity disappeared rapidly after operation. Both, testosterone or 5 alpha-dihydrotestosterone replacement restored the normal contractile function. Flutamide treatment caused also a decrease in the responses, but they were of inferior value than those obtained after surgical castration. Neither bilateral vasectomy nor bilateral epididymectomy caused alterations in the prostatic contractile behavior.

Anilides↗

Effects of prolactin and androgens on seminal vesicular lipids of castrated mature bonnet monkeys Macaca radiata.

Effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT) and the combination of these androgens with PRL/Br on the total lipid, total cholesterol, total glyceride glycerols, total phospholipid and their fractions in seminal vesicles of castrated mature monkeys were studied. Glyceride glycerols formed the major portion (50%) of total lipids in normal monkeys. Cholesterol and phospholipids were of equal share (25%). Esterified cholesterol formed major share (75%) of total cholesterol. Diacyl glycerol was the major (60%) glyceride glycerol and phosphatidyl choline and ethanolamine were the major phospholipid classes. Except triacyl glycerol castration markedly decreased all the lipid classes. PRL restored normal free and esterified cholesterol and phosphatidyl inositol but Br invariably decreased all the lipid classes. TP/DHT treatment stimulated the free and esterified cholesterol more than the control; it restored the normal glyceride glycerols. Phosphatidyl inositol, choline and ethanolamine were stimulated by androgens and other phospholipid classes were brought to normal. Addition of PRL + TP/DHT markedly increased esterified cholesterol, phosphatidyl inositol, choline, ethanolamine and phosphatidic acid. In all these aspects, Br counteracted the effects of androgens and PRL.

Animals↗

[Effect of neonatal castration on the capacity of the cerebral neurons in the septal complex of male rats to bind sex steroids].

The influence of neonatal castration on neuron capacity to bind septal dorsal, lateral and medial nuclei, Brock's diagonal fold nucleus and terminal streak bed nucleus of radiolabeled sex steroids (3H-testosterone and 3H-estradiol) was studied. Neonatal castration performed on the 1st day of male postnatal life raised the capacity of brain septal complex neurons to uptake sex steroids, mainly 3H-testosterone. The strategic position of the septal complex in the brain and the presence of neurons taking up actively sex steroids indicated an important role of this structure of the limbic system of the brain in the formation of neural mechanisms in the regulation of sex functions in male rats.

Aging↗

Combination therapy with flutamide and castration (orchiectomy or LHRH agonist): the minimal endocrine therapy in both untreated and previously treated patients with advanced prostate cancer.

One hundred fifty-four patients with clinical stage D2 prostate cancer with no previous endocrine therapy or chemotherapy received the combination therapy with the pure antiandrogen Flutamide and the LHRH agonist [D-Trp]LHRH ethylamide for an average of 22 months (3 to 49). The objective response to the treatment was assessed according to the criteria of the US NPCP. There was a 6.3-fold increase (29.2 versus 4.6%) in the percentage of patients who achieved a complete response as compared to the results achieved in 5 recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 4.5% of patients did not respond to the combination therapy as compared to an average of 18% by standard therapy. The duration of response is also significantly increased in the patients who received the combination therapy while the death rate was decreased by approximately 2-fold between 2 and 3 years of treatment. The marked (6.3-fold) improvement in the rate of complete objective responses coupled with the 4-fold decrease in the number of non responders, the increased duration of the positive responses and the 2-fold decrease in the death rate at 2 to 3 years of treatment are obtained with the combination therapy using Flutamide and castration with no or minimal secondary effects. In addition, two hundred nine patients with biopsy-proven stage D2 prostatic adenocarcinoma showing disease progression after orchiectomy, DES or an LHRH agonist used alone received the combination therapy with the pure antiandrogen Flutamide. In patients treated with DES, the estrogen was replaced by the LHRH agonist [D-Trp6]LHRH ethylamide. Objective response to therapy was also assessed according to the criteria of the US NPCP. Thirteen patients (6.2%) had a complete response to treatment while partial and stable responses were achieved in 20 (9.6%) and 39 (18.7%) patients, respectively, for a total objective response rate of 34.5%. The mean duration of response was 24 months. While, in the non responders, the median survival was 8.13 months with a 17% probability of survival at 2 years, the probability of survival of patients who showed partial and stable responses at 2 years was 87 and 67%, respectively. All patients who achieved a complete response are still alive. Considering the excellent tolerance coupled with an objective response observed in 34.5% of the patients, the combination therapy with Flutamide and castration (surgical or LHRH agonist) appears to be the treatment of choice for prostate cancer patients in relapse after standard endocrine therapy.

Adenocarcinoma↗

Concentrations of carnitine in the seminal fluid of normospermic, vasectomized, and castrated dogs.

Concentrations of total carnitine (free and esterified) were determined in seminal fluids from 12 normospermic dogs before treatment and from the same 12 dogs after assignment to control, vasectomized, or castrated treatment groups (4 dogs each). Before treatment, the mean concentration (+/- SD) of carnitine in seminal fluid was 946 +/- 345 nmol/ml and was not significantly different (P greater than 0.05) among groups on any seminal collection day. After surgery, mean concentrations of carnitine in seminal fluid from vasectomized and castrated dogs were 49 +/- 9 and 14 +/- 5 nmol/ml, respectively and were lower (P less than 0.001) than the mean concentration in control (sexually intact) dogs. Dogs with obstructive azoospermia may be distinguished from those with aspermatogenesis (secretory azoospermia) by measuring seminal carnitine concentration. Seemingly, the epididymis is the major source of carnitine in canine seminal fluid, because the concentration of carnitine in prostatic fluid was only 58 +/- 53 nmol/ml, whereas the concentration of carnitine in 6 pools of epididymal fluid was 18.8 +/- 3.9 mumol/ml.

Animals↗

Studies of instrumental behavior with sexual reinforcement in male rats (Rattus norvegicus): II. Effects of preoptic area lesions, castration, and testosterone.

We studied effects of lesions to the medial preoptic area (POA), castration, and testosterone replacement on instrumental and unconditioned sexual behavior in male rats. We achieved instrumental measures of sexual motivation by training males to work for an estrous female, presented in an operant chamber under a second-order schedule of reinforcement. POA lesions abolished mounts, intromissions, and ejaculation but did not disrupt instrumental responses, investigation of the female, or abortive mounting attempts. Castration abolished attempts to copulate and also caused a marked decrease in instrumental responses. Testosterone resulted in the prompt reinstatement of instrumental responses and more gradual recovery of unconditioned sexual behavior. We discuss these results in terms of the motivational and performance effects of these neuroendocrine manipulations.

Animals↗

Development of a gas chromatographic-mass spectrometric method using multiple analytes for the confirmatory analysis of anabolic steroids in horse urine. I. Detection of testosterone phenylpropionate administrations to equine male castrates.

A gas chromatographic-mass spectrometric (GC-MS) method using three analytes to detect and confirm the administration to equine male castrates of veterinary pro-drugs based upon esters of testosterone is described. The method involves extraction of steroid conjugates from horse urine by C18-bonded cartridges and fractionation into glucuronic acid and sulpho-conjugates by Sephadex LH-20 column chromatography. After deconjugation, the free neutral steroids were partially purified by thin-layer chromatography and following derivatization (methyloxime-trimethylsilyl ether) were analysed by capillary GC-MS in the selected-ion or full-scan mode. Of the three analytes, 5 alpha-androstane-3 beta, 17 alpha-diol could be detected in the glucuronic acid fraction for about ten days and 5 alpha-androstane-3 beta,17 beta-diol and testosterone could be detected in the sulpho-conjugate fraction for up to nineteen days after administration of a single therapeutic dose (50 mg) of testosterone phenylpropionate to cross-bred and thoroughbred castrated male horses. The reasons for development of such a method, its validation and its potential for the detection of neutral metabolites of other veterinary anabolic steroids in horse urine are discussed.

Animals↗

[Early changes in the dog prostate after castration. An ultrastructural study].

Using electron microscopic techniques the prostate glands of male Beagle dogs were studied 3 days after castration. At this time marked differences in the extent of alterations of the glandular epithelium were observed: Whereas several acini showed only minor changes with reduction of epithelial height and diminution of secretory granules, many acini were severely affected with pronounced alteration of cellular structure and accumulation of large lipid droplets. A constant feature was the stimulation of the basal cells of the grandular epithelium. Additionally, in some areas of the gland aggregations of stimulated basal cells forming an acinus-like structure with a slit-like lumen were found. Our study shows that castration leads to marked alterations of prostatic epithelium within a short time. Androgen deprivation causes regressive changes of secretory epithelial cells, but clearly stimulates the basal cell population.

Animals↗

Giant granular filamentous bodies in the cytoplasm of arcuate nucleus neurons of castrated rats.

We have performed an ultrastructural and quantitative study of granular filamentous bodies (GFBs) present in the cytoplasm of some arcuate nucleus neurons of rats of both sexes castrated at one month of age and sacrificed one or three months later, as well as untreated and sham-operated animals of the same ages. GFBs appear as round or ovoid cytoplasmic inclusions of granular-filamentous texture and generally lack a limiting membrane; their sizes vary from 0.7 to 2.8 microns (average 1.7 microns). GFBs are present more frequently in the perikarya, but they also occur in dendrites. In rats of both sexes castrated at one month of age and sacrificed three months later a noticeable finding was the presence of some giant GFBs, whose major axis could reach up to 6 microns. The nomenclature, the origin and the possible significance and function of GFBs are discussed.

Animals↗

Long-term sustained delivery of androgens by means of TCPL devices and the effect on high-density lipoprotein in castrated rams.

Several studies have established that conventional routes of androgens administration resulted in a decrease in high-density lipoprotein cholesterol (HDL-C), a major risk factor for coronary artery disease. The HDL-C response to the long-term sustained delivery of androgens by means of tricalcium phosphate-lysine implants (TCP-L) has not been investigated. Suffolk rams (40-57 kg) were used for this investigation. A total of 11 rams were castrated by elastrater rings at birth. At 7 months of age, these animals were randomly divided into three groups. Group 1 rams (n = 3) served as control group. Groups 2 (n = 4) and 3 rams (n = 4) were implanted subcutaneously into the axillary region with sterilized (ethylene oxide) TCP-L capsules, containing testosterone (T) and Dihydrotestosterone (DHT), respectively. Blood samples (5 ml) were collected from the experimental and control animals by jugular venipuncture weekly for 12 months. After blood samples were allowed to clot (12 hours), serum was separated by centrifugation and stored at -20 degrees C until analyzed. Circulating T and DHT levels were measured by solid-phase radioimmunoassay and HDL-C and protein by colorimetric method and lipoprotein fractions mobility by electrophoresis. The results demonstrated that after castration, the HDL-C concentrations increased significantly in all animals (P < .001). Sustained delivery of T (4-6 ng/ml) and DHT (1.5-2 ng/ml) produced a significant decrease in HDL-C (P < .001), in which was similar to HDL-C reductions seen when the animals were treated with DHT-TCPL (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗