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PubMed1981

Effects of short-term bilateral and unilateral castration and androgen replacement on the metabolism of [3H] testosterone in vitro by the epididymis of the immature rat.

The in-vitro metabolism of [3H] testosterone by the epididymis of the pubertal rat (55 days of age) has been examined after short-term bilateral and unilateral castration and androgen replacement. Bilateral castration did not decrease the metabolism of [3H] testosterone, but did result in a decline in the proportion of 5 alpha-dihydrotestosterone produced and an increase in that of 5 alpha-androstane-3 alpha, 17 beta-diol, androsterone and 5 alpha-androstane-3,17-dione. Changes in metabolism occurred in the caput within 2 days after surgery, but not until 5 days after surgery in the cauda epididymidis. Daily testosterone treatment, which maintained prostatic growth in bilaterally castrated animals, did not restore normal androgen metabolism and increased further the production of androsterone and 5 alpha-androstanedione by the cauda. In unilaterally castrated animals, androgen metabolism in epididymal tissue from the operated side was normal in the cauda but was indistinguishable in the caput from that of bilaterally castrated rats. These results indicate that (a) androgen metabolism by the caput, compared to that by the cauda, responds more quickly to androgen withdrawal and (b) that in the short term, normal androgen metabolism by the caput, but not the cauda, is dependent upon the presence of the ipsilateral testis. Furthermore, testosterone alone proved an inadequate replacement for bilateral castration which implies that the pubertal rat testis secretes additional compounds which are essential for normal function of the epididymis.

Animals↗
PubMed1984

Correlation between LH secretion in castrated rats with cellular proliferation and synthesis of DNA in the anterior pituitary gland.

The relationship between the release of LH and the synthesis of DNA was studied in the anterior pituitary gland of castrated rats. Cell types were characterized immunocytochemically. Castration significantly (P less than 0.01) increased the concentration of LH in serum (1326%) and the incorporation of [3H]thymidine into pituitary DNA (72%). This was accompanied by an increment in the activity of the enzyme DNA polymerase-alpha (58%) and in the number of mitoses (from 2 +/- 0.1/mm2 in intact rats to 21 +/- 0.8/mm2 15 days after castration). Only 20% of the mitoses found in the pituitary gland of castrated rats were positively stained with the antiserum against the beta-subunit of LH. The other 80% did not stain either with LH antiserum or with antisera against the other pituitary hormones. There was a significant (P less than 0.01) increase in the number of LH cells in castrated rats (48%). All the changes produced in the anterior pituitary gland after castration were prevented by the administration of dihydrotestosterone. The results demonstrate that a stimulation of LH release is followed by an increase of DNA synthesis and cell proliferation of gonadotrophs in the anterior pituitary gland.

Animals↗
PubMed1981

Mode of proliferation of gonadotrophic cells of the anterior pituitary after castration--immunocytochemical and autoradiographic studies.

There are three possibilities concerning the mechanism of increase in number of gonadotrophs in the anterior pituitary after castration: one is the cell division by mitosis of matured gonadotrophs, another is the differentiation of immature cells, and the third is conversion of some other cell types into gonadotrophs. In order to determine the above possibilities, light and electron microscopic examinations using a combination of immunocytochemistry and autoradiography were performed. Normal and castrated adult male rats were used. Morphometry indicated that a highly increased population of gonadotrophs reacted with anti-LH beta serum after castration. Increased numbers of mitoses and elevated incorporation of 3H-thymidine into the nuclear chromatin were observed in both anti-LH beta reactive cells and other pituitary cells after castration. Electron microscopic immunocytochemical observations demonstrated the presence of immature cells with a few immunoreactive secretory granules in the castrated pituitary. It is considered that mitosis is a major factor for proliferation of gonadotrophs in the anterior pituitary after castration, but the possibility of differentiation from immature cells into gonadotrophs cannot be ruled out. The third possibility could not be proven in this study.

Animals↗
PubMed2005

Effects of castration, tooth resection, or tail docking on plasma metabolites and stress hormones in young pigs.

Changes in the activity of the sympathetic nervous system or in the hypothalamo-pituitary-adrenal axis have been extensively used to evaluate pain induced by castration or tail docking in numerous species. Such data are missing in pigs. Therefore, three experiments were conducted to determine the effects of castration, tail docking, or tooth resection on stress hormones. Glucose and lactate also were measured because catecholamines stimulate mobilization of glycogen, which results in glucose and lactate release. In Exp.1, 18 male pigs from seven litters (two or three pigs per litter) were catheterized surgically into one jugular vein, under general anesthesia, at 5 or 6 d of age. Two days later, they were submitted either to bilateral castration, control handling, or no handling (n = 6 per group). Blood samples were collected before (- 15 and -2 min) and after (5, 15, 30, 60, 90, 180 min) the experimental treatment. In Exp. 2, 27 female pigs from 12 litters (one to four pigs per litter) were submitted either to tooth clipping with pliers, tooth resection with a grinder apparatus, control handling, or no handling (n = 6 or 7 per group) at 1 d of age. In Exp. 3, 17 female pigs from nine litters (one to three pigs per litter) were submitted to one of the following treatments: 1) tail docking with an electric-heated scissor docking iron, 2) control handling, and 3) no handling (n = 5 or 6 per group) at 1 d of age. Castration induced significant (P < 0.05) increases in adrenocorticotropin hormone (ACTH; from 5 to 60 min), cortisol (from 15 to 90 min), and lactate (from 5 to 30 min). These variations are indicative of stress and tissue damage following castration. In contrast, neither tail docking nor tooth resection had marked effects on plasma cortisol, ACTH, glucose, and lactate. Measurements of plasma cortisol, lactate, and ACTH could be useful for validating treatments designed to relieve the distress reaction induced by castration in pigs.

Adrenocorticotropic Hormone↗
PubMed2004

Preventive effects of D-004, a lipid extract from Cuban royal palm (Roystonea regia) fruits, on testosterone-induced prostate hyperplasia in intact and castrated rodents.

Benign prostatic hyperplasia (BPH) is the noncancerous, uncontrolled growth of prostate gland cells and stroma that can cause difficulty urinating. Fruit lipid extracts from saw palmetto, a palm from the Arecaceae family, are used for BPH management. The Cuban royal palm, Roystonea regia, is also a member of the Arecaceae family and therefore it was appropriate to investigate the protective effects of Roystonea regia fruit lipid extracts on prostatic hyperplasia. The aim of this study was to investigate whether D-004, a lipid extract from Roystonea regia fruits, prevented testosterone-induced PH in castrated and intact rodents. Two series of experiments were performed. The first one was conducted in castrated and intact rats, distributed into five groups of 10 rats per group. The negative control group was injected with soy oil and treated orally with vehicle, while the four testosterone-injected groups were treated with vehicle (positive control), D-004 100, 200 and 400 mg/kg, respectively. The other experiment was conducted in castrated and intact mice. These were distributed into four groups of 10 mice per group: a negative control group and three testosterone-injected groups, of which one was a positive control, while two received D-004 200 and 400 mg/kg, respectively. At study completion, the rodents were sacrificed and prostates removed and weighed. D-004 at doses of 100, 200 and 400 mg/kg significantly and dose-dependently prevented prostate enlargement in intact and castrated rats and mice. The percentage inhibitions obtained in mice were greater: 77% and 84% for intact and castrated mice, respectively. D-004 therapy did not affect body weight. It is concluded that D-004 administered orally significantly prevented testosterone-induced prostate enlargement in both intact and castrated rodents, indicating that an endogenous supply of testosterone is not necessary to observe such an effect The results of the present investigation support further studies of D-004 on experimental models of prostatic hyperplasia.

Animals↗
PubMed1990

Effects of neonatal and adult castration and of testosterone substitution in male rats on growth of enzyme-altered hepatic foci in the resistant hepatocyte model.

Marked sex differences in the growth of enzyme-altered hepatic foci have been observed in rats treated according to the "resistant hepatocyte model." The present study was performed to investigate the effect of neonatal and adult castration of male rats, with or without testosterone substitution, on the growth rate of foci during selection of initiated cells with 2-acetylaminofluorene and partial hepatectomy. Neonatal castration of male rats decreased focal growth to the same level as in female rats. Castration of adult male rats 2 wk before initiation with diethylnitrosamine also decreased the growth rate of foci, but less markedly than in neonatally castrated rats. Testosterone substitution of male rats castrated as neonates or as adults, from 10 days after initiation with diethylnitrosamine, restored focal growth to that of sham-castrated controls. Previous investigations concerning the role of gonadal hormones in sex differentiation of various liver functions indicated a role of the hypothalamo-pituitary-liver axis in mediating the effects of androgens. It is therefore also suggested that the effects of androgens on early steps of hepatocarcinogenesis observed in the present study are mediated by similar mechanisms, possibly through an influence on the metabolism of 2-acetylaminofluorene.

2-Acetylaminofluorene↗
PubMed1977

Effect of neonatal castration on the content of hypothalamic LHRH, pituitary LH and plasma LH in developing male rats.

The content of hypothalamic LHRH and concentration of LH in pituitary and plasma were measured on day 5, 7, 10, 14, 17, 22, 25, 30, 45, 52 and 60 in male rats which were bilaterally castrated on day 2. The levels of plasma LH were significantly higher in all the groups of castrated rats than in normal male rats of corresponding ages. The concentration of plasma LH did not rise progressively but showed day to day fluctuation apparently due to alteration of sexual differentiation of the hypothalamus. The concentration of pituitary LH was significantly lower in neonatally castrated rats compared to normal male rats except on days 17, 25 and 30. The content of hypothalamic LHRH declined initially following castration, but from day 17 onwards significantly higher levels of hypothalamic LHRH were maintained in neonatally castrated rats than in intact control. Initial decline in the content of hypothalamic LHRH may be because of stimulation of release of LHRH which exceeds maximal rate of synthesis and subsequent increase in the content of hypothalamic LHRH may be due to enhanced LHRH synthesis as a result of castration.

Aging↗
PubMed1986

Effects of neonatal and adult castration on the in vitro metabolism of steroids and xenobiotics in rat liver.

Previous studies in our laboratory have shown that the sex-differentiated metabolism of 4-androstene-3,17-dione and of several other steroid hormones in adult rat liver is "feminized" following neonatal castration of male rats, due to an influence via the hypothalamo-pituitary-liver axis. The metabolism of many xenobiotics is also sex differentiated, and an important question is whether endocrine ablations might alter hepatic carcinogen metabolism in a way explaining, for example, the decreased tendency of castrated male rats [Y.C. Toh, In: Shanmagarathnam et al. (eds.), Liver Cancer, Cancer Problems in Asian Countries, Proceedings of the Second Asian Cancer Conference, pp. 167-171. Singapore: Singapore Cancer Society, 1976] to form liver tumors following 2-acetylaminofluorene treatment. The results presented in this paper clearly show that neonatal castration of male rats, much more efficiently than adult castration, feminizes the cytochrome P-450-dependent, sex-differentiated, liver microsomal formation of 7-hydroxy-2-acetylaminofluorene, 9-hydroxy-2-acetylaminofluorene, 5-hydroxy-2-acetylaminofluorene, 1-hydroxy-2-acetylaminofluorene, and N-hydroxy-2-acetylaminofluorene from 2-acetylaminofluorene as well as the total microsomal formation of benzo(a)pyrene metabolites (male greater than female). O-Deethylation of 7-ethoxyresorufin was neither sex differentiated nor affected by castration. The capacity for in vitro sulfation of N-hydroxy-2-acetylaminofluorene in the postmicrosomal supernatant, markedly sex differentiated in the rat (male greater than female), was completely feminized by neonatal but not by adult castration. The results suggest that the influence of endocrine ablations on chemical carcinogenesis in rat liver might be mediated via the hypothalamo-pituitary regulation of certain pathways of hepatic xenobiotic metabolism.

2-Acetylaminofluorene↗
PubMed1979

[Studies on the kinetics of the RNA metabolism in the prostate of normal and castrated rats (author's transl)].

In the prostate of adult Wistar rats the RNA/DNA quotient of the whole organ as well as the amount of RNA and DNA in the nucleus was measured at different times after castration. Furthermore the half-life time for the turnover of the RNA in the nucleus and the cytoplasm was determined for normal and castrated rats with the aid of pulse labelling using [5(-3)H]uridine. A mathematical model was developed to analyze the experimental results. This model enabled us to make differentiated statements on the heterogeneous nuclear RNA (hmRNA) and the remaining RNA in the nucleus. The evaluation of the experimental values gave the following results: 1. By deprivation of androgens the uptake of [3H]uridine into the prostate is lowered. 2. The amount of DNA in the morphologically intact nucleus remains constant at least up to the 12th day after castration. 3. 6 days after castration the amount of hmRNA decreases to 1/10 and that of cytoplasmic RNA to 1/4. 4. The half-life time for the decrease of the whole nuclear RNA is 3.7 d and that of the cytoplasmic RNA 1.7 d. 5. The half-life time for the turnover of hmRNA is 16 min and that of cytoplasmic RNA about 2 days. 6 days after castration the half-life times are unchanged. The experimental results suggest that the observed decrease of nuclear RNA following castration can mainly be attributed to a reduced synthesis of hnRNA, while the decrease of cytoplasmic RNA is first of all caused by an increase in RNA degradation.

Animals↗
PubMed1979

Serum sex hormone binding globulin and testosterone binding after estradiol administration, castration, and their combination in men with prostatic carcinoma.

We measured serum sex hormone binding globulin (SHBG) binding capacity, the index of testosterone binding to SHRG, and the serum concentrations of testosterone, 5 alpha-dihydrotestosterone, and estradiol in 16 patients treated for advanced prostatic carcinoma in order to evaluate the effectiveness of various therapeutic regimes in reducing total and biologically active androgen in blood. Polyestradiol phosphate (Estradurin, 80 mg im as a monthly injection) treatment alone is not as efficient as castration in reducing serum testosterone and 5 alpha-dihydrotestosterone. There was no clear difference between the castration and combination treatment (castration followed by polyestradiol phosphate administration) groups in this respect. It is apparent that Estradurin treatment alone and in combination with castration results in small but significant increases in SHBG binding capacity, whereas this parameter did not alter after castration alone. All three forms of treatment resulted in relatively similar significant increases in the index of testosterone binding to SHBG. The rather mild effect of Estradurin on the parameters measured may be attributable to the binding of the exogenous estradiol to SHBG, which thus greatly reduces its biologic activity. We concluded that castration is clearly more effective in reducing the amount of biologically active testosterone than Estradurin and the combination of these treatments has little influence on further reducing total or biologically active circulating testosterone.

Aged↗
PubMed1983

Induction of hepatic tumors by diethylstilbestrol alone or in synergism with n-nitrosobutylurea in castrated male WF rats.

Inbred male WF rats were castrated at 40 days of age and divided into 5 groups. Group I was given no further treatment. Groups III, IV, and V received pellet implants of 5.0 mg diethylstilbestrol (DES) concurrently with castration. At 50-55 days of age, groups II, IV, and V were given drinking water containing 5.0 mg N-nitrosobutylurea (NBU) per day for 30 days (subthreshold dose). At the termination of NBU treatment, group V further received daily sc injections of 2-bromoergocryptine (CB-154; 0.4 mg/100 g body wt) four times a week throughout the experiment. None of castrated rats or rats castrated and treated with NBU alone developed hepatic tumors (HT) and pituitary tumors (PT). Incidences of HT and PT in groups III, IV, and V were 4/9 (44%) and 7/9 (78%), 15/17 (88%) and 12/17 (71%), and 17/20 (85%) and 4/20 (20%), respectively. The treatment of DES alone resulted in the concurrent development of HT and PT in castrated male rats (group III), and further NBU treatment significantly increased the incidence of HT (group IV). CB-154 treatment did not change the incidence of HT, the number of HT per rat, and the liver weight, although it significantly reduced the incidence of PT, the pituitary weight, and the serum prolactin level in castrated male rats given DES and NBU (group V). These results indicate that DES itself had a direct carcinogenic effect on the liver; this effect was not mediated by prolactin, and NBU increased the effect of DES in this process.

Animals↗
PubMed1984

Effects of castration, with and without testosterone replacement, on leg bone integrity in the domestic fowl.

Studies were conducted to assess the effects of castration on leg bone integrity of male White Leghorn chickens. Eighteen 5-week-old males were randomly allocated to 3 groups: group 1--intact controls, group 2--castrated, and group 3--castrated and subsequently treated with testosterone (T)-filled Silastic capsule implants. Body weight and plasma concentrations of luteinizing hormone, androgens, and total calcium were measured in each bird at intervals throughout the experiment. Subsequently, radiographs were performed upon the tibiotarsus-tarsometatarsus region of the left limb of birds from the 3 treatment groups at 7, 35, and 47 weeks of age and assigned a score of 1 to 3 (1 = normal; 3 = greatest pathologic change). Analysis of radiologic scores indicated that at 35 and 47 weeks, castrated birds (group 2) had a mean score significantly greater than that of control birds (group 1). The abnormality was typified by hyperossification with exostoses in the ossified tibial cartilage and lateral calcaneal ridge. In contrast, radiologic scores from individual T-implanted castrated birds (group 3) at 35 and 47 weeks were more variable, but the mean score was not statistically different from that of the control group. We conclude that the depression of circulating concentrations of sex steroids, by castration, in young male chickens results in hypercalcification of the tibiotarsus-tarsometatarsus region of the limb. This effect appears to be mediated directly or indirectly by T or a metabolite of T.

Animals↗
PubMed1982

Influence of castration upon trophism and reactivity of rat seminal vesicles.

1. Castration-induced time-dependent changes in trophism and reactivity of rat seminal vesicles were studied by measuring vesicle weight, spontaneous contractility, apparent sensitivity (pD2) to acetylcholine and acetyl-beta-methylcholine and intrinsic reactivity (alpha) to acetyl-beta-methylcholine 5, 10, 15 and 30 days after surgery. 2. The wet and dry weights of the seminal vesicles from castrated rats were less than those from the controls 5 days after castration, and decreased with time after gonadectomy. Spontaneous contractility was observed 15 days after surgery. The pD2 for acetyl-beta-methylcholine was significantly higher than normal control values (5.81 +/- 0.09 vs. 5.34 +/- 0.12) 10 days after orchidectomy, whereas the change in sensitivity to acetylcholine (from 5.04 +/- 0.15 to 5.95 +/- 0.95) was detected only 30 days after castration. In contrast, a change in alpha from 0.75 +/- 0.04 (normal control) to 0.90 +/- 0.02 was detected on the 5th day after castration. 3. These data show that atrophy and spontaneous contractility of rat seminal vesicles, as well as increased sensitivity and reactivity to parasympathetic drugs are detectable at different times after castration.

Acetylcholine↗
PubMedDate not supplied

Effects of sialoadenectomy and castration in female rats.

Previous work on the role of the submaxillary glands in the control of the oestrous cycle in rats has been extended to castrated rats in order to avoid the overlapping between sexual and salivary hormones. Animals were sacrificed 30 days after sialadectomy or pseudosialadectomy. The data show that simultaneous castration and sialadectomy increases significantly the glucaemia level and decreases the weight of the adrenal glands. Non-simultaneous castration and removal of the submaxillary glands decreases the weight of the parotid glands. This effect decreases when both actions are simultaneous. On the other hand, castration produces an important decrease in QO2 uptake in tested structures. Removal of submaxillary glands produces a significant increase of QO2 in hypothalamus and thyroid glands. Simultaneous castration and sialadectomy at the anterior cortex, posterior cortex and parotid gland level shows similar results with respect to desalivated rats; other structures show results similar to the castrated group values. From these results, the role played by submaxillary glands in the control of the sexual cycle of the rat and the possible relation to other structures is discussed.

Adrenal Glands↗
PubMed1980

Spontaneous contractions and membrane activity of castrated guinea-pig vas deferens.

Castration of the guinea pig was followed by atrophy of the vas deferens and appearance of spontaneous contractions. Testosterone replacement reversed those effects and diethylstilbestrol treatment increased them. A month after castration or castration and stilbestrol treatment (15 mg/30 days), the membrane exhibited depolarization and spontaneous spikes that were not seen with the normal groups. The spontaneous contractions observed with both groups reflected the occurrence of membrane spikes. Tetrodotoxin (3 c 10(-6) M) did not change the membrane potential in any organ studied nor did it affect the pattern of spontaneous contractions. Verapamil (5 x 10(-6) M) increased the membrane potential of the muscles from castrated and stilbestrol-treated castrated animals, abolished the membrane spikes and blocked the spontaneous contractions. The results suggest that castration increases calcium permeability through the membrane. The increase in calcium permeability would be responsible for muscle rhythmicity.

Animals↗
PubMed1994

The effect of castration on dopamine receptor sensitivity in male young rats: behavioral and neurophysiological studies.

The effect of castration on the sensitivity of dopamine (DA) receptor to low doses of apomorphine was investigated using drug discrimination task and neurophysiological recording of the firing rate of DAergic neuron in the substantia nigra pars compacta in male young Wistar rats. In the behavioral study, castration did not change the dose-response curve for apomorphine (ip) discrimination (the ED50 values in sham-operated and castrated animals were 45.2 and 47.1 micrograms/kg, respectively). In the neurophysiological study, the inhibitory effect of apomorphine (iv) on the firing rate of DAergic neuron in the substantia nigra pars compacta was significantly enhanced by castration (the ED50 values in sham-operated and castrated animals were 6.15 and 2.96 micrograms/kg, respectively). These results suggest that castration does not change post-synaptic DA receptor sensitivity, whereas it potentiates the sensitivity of pre-synaptic DA receptor to low doses of apomorphine in the substantia nigra.

Action Potentials↗
PubMed1994

[Relationship between the converting ability of liver microsomes and monocrotaline-induced pulmonary hypertension in male, female and castrated male rats].

It is well known that the initial reaction of monocrotaline-induced pulmonary hypertension in rats (MPH) is injury to the endothelial cells of pulmonary vascular bed by monocrotaline-pyrrole (MP), which is converted from monocrotaline (M) by cytochrome P450 monooxygenase in hepatic microsomes. It is also known that the degree of MPH differs between sexes. The mechanisms of MPH remain, however, to be elucidated. The purpose of this study is to clarify the relationship between the converting ability of hepatic microsomes and the sexual difference in MPH using castrated male rats. A 40 mg/kg dose of M was given to fifteen 6 week-old male, twelve 6 week-old female and fifteen 6 week-old castrated male, Sprague-Dawley, rats. The castration was done at three weeks of age. Four weeks after M administration, the right ventricular systolic pressure (RVSP) and the right ventricular to total ventricular weight ratio (RV/T) were measured as indices of pulmonary hypertension. Livers were taken from six 6 week-old male, six, 6 week-old female and six 6 week-old castrated male, Sprague-Dawley, rats and then homogenized and centrifuged to extract hepatic microsomes. M, at 3.3 mM, was added to concentrated hepatic microsomes (0.25 to 1.5 mg/ml) in order to produce MP. The concentration of the MP was measured using a modification of Mattock's method. The mean value of RVSP was 86.5 mmHg in males, 59.6 mmHg in females and 73.9 mmHg in castrated males. The mean value of RV/T was 0.453 in males, 0.358 in females and 0.403 in castrated males.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The influence of castration on pharmacologically induced penile erection in the cat.

The purpose of this study was to investigate the in vivo effects of intracavernosal injections of adrenomedullin (ADM), calcitonin gene-related peptide (CGRP), nociceptin, vasoactive intestinal polypeptide (VIP), sodium nitroprusside (SNP), and prostaglandin E1 (PGE1) on penile erection in castrated and intact (control) anesthetized cats. Erectile responses to ADM, CGRP, nociceptin, VIP, SNP, and PGE1 were compared with responses to a standard triple-drug combination (1.65 mg of papaverine, 25 microg of phentolamine, and 0.5 microg of PGE1) in both castrated and control cats. In control animals, ADM, CGRP, nociceptin, VIP, SNP, and PGE1 induced penile erections similar to those elicited by the triple-drug combination. However, in castrated animals, there was a significant decrease in erectile response; the response to intracavernosal injection of the standard triple-drug combination in castrated cats was 28% of that of the control group of animals. Serum testosterone levels demonstrated a significant (P < 0.0001) positive correlation (r = 0.52) with intracavernosal pressure in response to the standard combination. A marked reduction in serum testosterone levels was observed in castrated cats when measured by radioimmunoassay (0.34 +/- 0.1 ng/dl in castrated cats, compared with 31.15 +/- 6 ng/dl in control cats). These data suggest that the presence of testosterone is a necessary prerequisite to sustain a pharmacologically induced penile erection in the cat.

Alprostadil↗