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The vasopressinergic innervation of the brain in normal and castrated rats.

A detailed description is given of the distribution of vasopressin-immunoreactive structures in the brain of intact adult male rats. By application of a modified immunocytochemical procedure, vasopressin-immunoreactive fibers were detected in many new areas. In adult male rats which were castrated 15 weeks before death, vasopressin-immunoreactive cell bodies had disappeared from the bed nucleus of the stria terminalis and the medial amygdaloid nucleus. No obvious changes were found in vasopressin-immunoreactive cell bodies in other areas. Furthermore, a very strong reduction was seen in the density of vasopressin-immunoreactive fibers in the olfactory tubercle, nucleus of the diagonal band and its immediate surroundings, ventral pallidum, basal nucleus of Meynert, lateral septum, septofimbrial nucleus, ventral hippocampal formation, amygdaloid area, pre- and supramammillary nucleus, supramammillary decussation, (inter)dorsomedial, parafascicular, and ventral aspect of paraventricular thalamic nuclei, zona incerta, lateral habenular nucleus, ventral tegmental area, substantia nigra, periventricular gray, dorsal and median raphe nucleus, and locus coeruleus. No changes were observed in other areas containing vasopressin-immunoreactive fibers. These changes following gonadectomy were not observed in castrated rats which had been treated with testosterone. The results suggest that vasopressin projections from the bed nucleus of the stria terminalis and possibly from the medial amygdaloid nucleus require the presence of gonadal hormones for their normal appearance. This is in contrast to pathways arising from the hypothalamic vasopressin-producing nuclei, which fail to show obvious changes following castration.

Animals↗

Adrenalectomy and castration in the genetically obese (ob/ob) mouse.

The present studies have tested the hypothesis that adrenalectomy could modify the phenotypic expression of genetic obesity by examining the effects of adrenalectomy on the function of the gonadal system in lean and ob/ob mice. Corticosterone concentrations were undetectable in the adrenalectomized animals. Adrenalectomy significantly slowed the weight gain of obese mice in comparison to sham-adrenalectomized controls. Gonadectomy had no independent effect on weight gain. The testes, prostate, and seminal vesicles in the ob/ob mice were significantly smaller than in the lean animals. Castration lowered the weights of the prostate and seminal vesicles in the lean mice to weights close to those observed in the castrated ob/ob mice. Castration significantly increased the concentrations of LH and FSH in both ob/ob and lean mice, but the absolute concentrations were higher in the lean mice in both conditions. Adrenalectomy per se had no effect on the concentration of LH, FSH, or testosterone or on the weights of the prostate or seminal vesicles. These data indicate that adrenalectomy has no effect on the physiologic control of the reproductive system in genetically obese mice, and are consistent with the hypothesis that the defect in the ob/ob mouse is a modulator of steroid action which over expresses glucocorticoid effects and under expresses gonadal steroid effects.

Adrenal Glands↗

The effect of castration and estrogen therarapy on serum high-density lipoprotein cholesterol.

The effect of castration on serum high-density lipoprotein (HDL) cholesterol was studied in 11 women with fairly regular menstruation. The HDL cholesterol levels before and one month after castration did not differ significantly. The effect of intramuscular estrogen therapy on HDL cholesterol was investigated in six castrated women. Ten days after injections of both 10.0 mg of estradiol valerate and 2.5 mg of estradiol benzoate plus 10.0 mg of estradiol phenylpropionate, HDL cholesterol was increased significantly. Fifteen days later, HDL cholesterol levels returned to the pretreatment values.

Castration↗

Influence of estradiol on accessory reproductive organs in the castrated male rat. Effects of bromocriptine and flutamide.

Estradiol partially maintained the weights of the dorsolateral prostate and seminal vesicles in castrated adult male rats. One group of animals received subcutaneous injections of estradiol (0.01 mg/kg) daily, while a second group of animals received estradiol plus bromocriptine (4.0 mg/kg). Changes in weights of accessory reproductive organs were correlated with serum prolactin levels. Estradiol significantly increased serum prolactin levels while concomitant treatment with bromocriptine caused serum prolactin to remain at castrate levels. Bromocriptine slightly decreased, but did not abolish, the effect of estradiol on weights of the dorsolateral prostate and seminal vesicles. To determine if the effect of estradiol was mediated by androgen receptors in the dorsolateral prostate and seminal vesicles, a third group of animals was treated with flutamide. Flutamide, at a dosage (20 mg/kg) that abolished the effects of dihydrotestosterone on the weights of these tissues, produced no alternation of the effects of estradiol. Treatment of animals with a combination of flutamide, bromocriptine, and estradiol did not significantly alter organ weights from the results obtained with bromocriptine and estradiol. Scatchard plot analysis of the effect of estradiol treatment on cytosol binding of estradiol demonstrated increased quantities of estradiol binding in dorsolateral prostate and seminal vesicles which correlated with the changes in weights noted. Although part of the effect of estradiol on regression of male accessory reproductive organs of castrated rats may be mediated by prolactin, the principal effect appears to be a direct action on responsive tissues.

Anilides↗

The effect of metabolites of testosterone on the development of fertilizing ability by spermatozoa in the epididymis of castrated hamsters.

The effects of testosterone, 17beta-hydroxy-5alpha-androstane-3-one (5alpha-dihydrotestosterone; 5alpha-DHT), 5alpha-androstane-3alpha, 17beta-diol (3alpha-androstanediol; 3alpha-diol) and 5alpha-androstane-3beta, 17beta-diol (3beta-androstanediol; 3beta-diol) on the development of fertilizing ability by spermatozoa in the epididymis were compared in castrated hamsters. The left corpus epididymidis was ligated for 14 days in intact and castrated animals to prevent the in-flow of spermatozoa into the cauda epididymidis and the ductuli efferentes were bilaterally ligated. The fertilization rate of spermatozoa in the left cauda epididymidis of control animals decreased to 71.1% after 14 days whereas that of spermatozoa in the unobstructed right cauda epididymis remained at the control level of 100%. After castration, 50 mug testosterone, 25 mug 5alpha-DHT and only 9 mug 3alpha-diol/day were the minimal doses that facilitated normal development of fertilizing ability but 75 mug testosterone, 37.5 mug 5alpha-DHT and 12.5 mug 3alpha-diol/day were required to maintain sperm survival at the control level. However, 3beta-diol was ineffective for both sperm maturation and survival.

Androgens↗

Cell proliferation and apoptosis in prostate tumors and adjacent non-malignant prostate tissue in patients at different time-points after castration treatment.

BACKGROUND: Androgen ablation is the standard treatment for advanced prostate cancer but the short-term cellular effects are largely unknown. METHODS: Sextant prostate biopsies were taken from 77 prostate cancer patients before and 1-10 days after castration treatment. Apoptosis, cell proliferation, and morphology were studied in malignant and non-malignant tissue, using stereological and immunohistochemical methods. RESULTS: Epithelial cell proliferation was significantly decreased both in non-malignant and malignant epithelium already 1 day after therapy. It remained low until day 7, but increased thereafter in the remaining non-malignant epithelial cells and in some tumors. Epithelial cell apoptosis was significantly increased during the first week and then returned to basal levels. The maximal apoptotic indexes, seven- and two-times the intact levels in the non-malignant and malignant glands, respectively, were found at days 3-4 or even earlier in the tumors. Signs of tumor shrinkage such as glandular collapse and decreased tumor cell size were observed from day 3 in most tumors. DISCUSSION: The present study shows that the magnitude and kinetics of the response to castration in the normal human prostate is very similar to the response previously described in rodents. We also demonstrate that most human prostate tumors rapidly respond to castration indicating the need for further evaluation of when and how to best monitor the effects of hormone ablation therapy in prostate cancer patients.

Aged↗

Ultrastructural changes of sebaceous glands in castrated and testosterone-treated male rats. A qualitative and quantitative study.

The effect of testosterone on the sebaceous gland was studied in the male rat. Biopsies of dorsal skin from intact rats, from rats four weeks after castration, and from castrated rats treated with testosterone propionate for three weeks at a dose of 250 micrograms/kd/day (s.c.) were examined by electron microscopy. In the treated animals intermediate sacrifices were performed on days 4, 7, 14, 21. Stereology was used for a morphometric analysis of the smooth endoplasmic reticulum (SER). The presence of a vesicular endoplasmic reticulum throughout the cytoplasm of differentiating cells was observed in the sebaceous glands of intact rats. Following castration there was a shrinkage of these cells and a striking decrease in the volume density of the endoplasmic reticulum vesicles. The administration of testosterone to gonadectomized rats resulted in an increase in vesicle content above the normal level from the first week as revealed by stereological analysis. This study confirms the trophic effect of the androgen on the sebaceous gland at a subcellular level. Furthermore, it is shown that stereology is a useful method for detecting early hormone-induced changes and could be valuable for studying the effects of anti-androgens on this gland.

Animals↗

Ultrastructural evidence of gonadotrophin release from castration cells following injection of LHRH in the rat.

To examine the morphological evidence of the nature of hormone release from castration cells the author gonadectomized neonatal male and female rats. Twenty-eight days after the operation the animals were pretreated with estrogen, progesterone, or estrogen and progesterone in combination, every other day for one week, and then injected with LHRH 30 min before sacrifice. The administration of LHRH elevated remarkably the serum levels of gonadotrophins (LH and FSH) of neonatally gonadectomized rats. The steroid-pretreated animals showed higher serum levels of gonadotrophins than controls. Simultaneously, active exocytosis of secretory granules was observed in the hypertrophic gonadotrophs or castration cells of neonatally gonadectomized and steroid-treated rats following the injection of LHRH. These results indicate that hypertrophic gonadotrophs or castration cells also release hormone(s) by exocytosis of secretory granules.

Animals↗

Influence of castration followed by administration of LH-RH on the ultrastructure of rat pinealocytes.

The ultrastructure of adult male rat pinealocytes was studied after orchidectomy and orchidectomy followed by LH-RH administration. Castration causes an increased development of the rough endoplasmic reticulum and the Golgi apparatus as well as an increase in the number of lipid droplets and lysosomes. The changes after orchidectomy followed by LH-RH administration were more marked than after castration alone. The ultrastructural features observed after castration can be interpreted as a morphological equivalent of increased protein synthesis. The observations reported appear to indicate mutual interaction between the pineal organ and the hypothalamo-hypophyseo-gonadal system. A working hypothesis is put forward implying the presence of a negative feedback mechanism between the pineal and the adenohypophysis.

Animals↗

The ultrastructure of the male and female prostate of Praomys (Mastomys) natalensis. I. Normal, castrated and ovariectomised animals.

Male ventral and female prostates of Praomys (Mastomys) natalensis were examined with the electron microscope. The findings support and add to information obtained with the light microscope on tissues from normal, castrated and ovariectomised animals. Our results indicate that although the female prostate may be considered a homologue of the male ventral ventral prostate anatomically and histologically, there are differences in sub-cellular morphology and hormone dependence. Cells of the intact ventral prostate of the male are characterised by prominent dilated Golgi vesicles and electron-dense "mature secretory granules" seen in the apical region of the cell. In the cells of the female prostate these features are absent. These morphological differences reflect the influence of hormones upon the cells, as shown by the reduction of the dilated Golgi vesicles in the castrated male and conversely, their occasional presence in the cells of the oestrous female. Comparison of castrated and ovariectomised animals shows that the male ventral prostate is much more dependent on androgens than the female is on ovarian hormones. There are several modes of secretion in the male ventral and the female prostate. These are by acellular and cellular blebbing, by a variety of secretory vesicles into the acinar lumina, and by a system of "double walled" vesicles not previously described.

Animals↗

Effect of castration and testosterone administration on the neuromuscular junction in the levator ani muscle of the rat.

The ultrastructure of the neuromuscular junction (n.m.j.) of the androgen-sensitive levator ani muscle was studied in normal adult male rats, in 8-month-old rats castrated at the age of one month and in castrated rats treated with testosterone propionate (TP). Castration does not result in significant changes of the n.m.j. The density of synaptic vesicles and the postsynaptic junctional folds remain practically normal inspite of marked atrophy of the muscle. TP administration for 7 days results in marked changes in pre- and postsynaptic structures. There is slow progressive depletion of synaptic vesicles, appearance of cisternae and coated vesicles in axon terminals, and coalescence of coated vesicles with the plasma membrane. Coated vesicles are also found inside Schwann cells and among junctional folds. Dense core vesicles appear both in the axon terminals and in the postsynaptic area. Collateral sprouting of terminal axons with the formation of new immature junctions is observed. After 35 days of TP administration depletion of synaptic vesicles continues. Glycogen beta-particles, mostly freely dispersed, occasionally seen in axon terminals 7 days after TP administration, subsequently increase in number. In the endplate zone of the muscle fibre increased protein synthesis is indicated by a rapid increase in ribosomes and irregularly located myofilaments and myofibrils. The appearance of n.m.j. after testosterone administration resembles that described after nerve stimulation; the degree of change is however less pronounced.

Animals↗

Influence of castration on incorporation of exogenous peroxidase into "synaptic" vesicles of the median eminence. II. The perivascular part of the palisade zone in male rats.

In the median eminence of male rats, nerve profiles in the immediate vicinity of portal capillaries have been divided into 4 categories on the basis of their vesicular content: profiles a with agranular "synaptic" vesicles of about 50 nm, b with similar agranular vesicles and also with granular vesicles of mainly 60-140 nm, c with granular vesicles alone and d without vesicles. Twenty-four hours after castration, the percentage of profiles of category a was significantly increased when compared with sham-operated animals, whereas the percentage of profiles of category b was significantly decreased. After intravenous injection of exogenous peroxidase, especially the nerve profiles located in direct contact with the outer basement membrane of the portal capillaries contained peroxidase positive "synaptic" vesicles. Injection off peroxidase after castration resulted in a significant increase in the percentage of nerve profiles containing both peroxidase positive and peroxidase negative "synaptic" vesicles (category a). It is suggested that, in certain nerve terminals, castration may lead to release off the content of granular vesicles, which may contain gonadotropin releasing factor. This release then may cause that nerve terminals with agranular vesicles and granular vesicles (category b) change in their vesicular content and are therefore classified as terminals with only agranular vesicles (category a). An increased turnover rate in the ultrastructurally affected terminals may be reflected in increased uptake of exogenous peroxidase. The observations imply that certain neurones projecting to portal capillaries in the median eminence are, directly or indirectly, sensitive to changes in the level of gonadal steroids.

Animals↗

Antagonistic reaction of the periportal and perivenous zone in the rat liver after castration and estrogen treatment. Histochemical and biochemical studies on G6PDH and malic enzyme activity.

G6PDH and ME activity was determined biochemically in homogenates and demonstrated histochemically in cryostat sections of rat liver. Control animals were sham-operated, the male and female rats of the experimental groups were castrated. After castration groups of rats were treated with daily doses of 3 or 6 micrograms/estradiol benzoate for 21 days. The results show that in the controls there is a sex-dependent distribution pattern of the two enzymes; in males the rather low activity is mainly located in the periportal area, in females the higher activity is demonstrable in the perivenous area. After castration G6PDH activity (and to a lesser extent ME activity) increases, mainly in the periportal zone. Estrogen treatment results in the high activity of both enzymes, which are exclusively located in the perivenous zone. In the periportal zone no G6PDH or ME activity is demonstrable histochemically. This zone-typical effect of estrogen is interpreted in terms of the concept of Metabolic Zonation, according to which it is supposed that the NADPH generating enzymes in the perivenous area have a lipogenic function whereas the periportal activity contributes to bile acid production.

Animals↗

Metabolism of testosterone 4-14C in skin of castrated rats.

Testosterone metabolism was studied in the skin and preputial glands of normal and prepuberally castrated male rats during the 2nd hair cycle. In catagen-telogen the 17-beta-OHSDH of dorsal skin was higher in castrated than in control animals; 5-alpha-reductase instead, remained unchanged through out the hair cycle. Also in the preputial glands of castrated rats 17-beta-OHSDH was higher than in normal rats. So was 5-alpha-reductase. A possible direct control of a substrate, like Testosterone, and/or of a hypophyseal tropin, like prolactin, on enzymes that direct the metabolism of steroids in target tissues is conceivable.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Peripheral autonomic regulation of gonadotropin secretion in pubertal rats. Inhibition of post-castration rise of gonadotropins during wallerian degeneration after sympathetic superior cervical ganglionectomy.

Shortly after superior cervical ganglionectomy (SCGx) peripheral sympathetic nerve terminals in the median eminence degenerate, the neurotransmitter is released, and a transient period of increased postsynaptic ensues. The present experiments were undertaken to examine, in the anterograde degeneration paradigm after SCGx, the participation of peripheral sympathetic nerves in feedback regulation of gonadotropin release in pubertal rats. Groups of 18 days old or 26 days old rats of both sexes were subjected to castration or its sham-operation, and 4 h later to SCGx or sham-SCGx. Twenty-four h later, the rats were decapitated and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were measured by RIA. In 19 days old male rats, the post-castration increase of circulating LH, but not of FSH, was prevented by the wallerian degeneration of sympathetic nerves after acute SCGx. At the 27th day of life, acute SCGx prevented FSH, but not LH, post-orchidectomy rise. In female rats, SCGx blunted the oophorectomy-induced increase of gonadotropin levels at both examined ages. SCGx brought about a significant decrease of serum LH levels in 19 days old, sham-castrated female rats. At the 19th day of life, acute SCGx decreased serum LH and FSH in neonatally orchidectomized rats, but not in neonatally androgenized female rats. The data are in favor of a negative influence of peripheral sympathetic neurons on gonadotropin release in prepubertal rats, predominantly in female rats.

Age Factors↗

Influence of castration and testosterone replacement on hypothalamic tyrosine hydroxylase activity in the rat.

Hypothalamic tyrosine hydroxylase (TH) activity of castrate rats is modulated by testosterone propionate (TP) in vivo. Kinetic studies revealed that both Vmax and Km were virtually unaltered for substrate tyrosine in the presence of an excess of DMPH4 cofactor. TP replacement to castrate rats increased the Km for added DMPH4 cofactor, while Vmax decreased. These results suggest that TP decreases TH activity of castrate rats by inhibiting the enzyme-reduced pteridine cofactor complex.

Animals↗

Persistence of infradian body weight cycles in castrated dormice (Glis glis).

Male dormice were castrated at 2 phases of their infradian body weight cycles. No consistent changes were found in cycle period, amplitude, or absolute weights of the dormice following castration. Unlike other mammals, body weights of dormice appear unaffected by castration. Although both body weight and reproductive condition vary on an infradian basis, the changes in body weight appear to be programmed independently from changes in gonadal function.

Animals↗

Histamine levels in mouse tissues: influence of castration.

The influence of castration on histamine levels in mouse tissues was investigated in Swiss mice. Only in female mice castration led to a significant decrease in the histamine content of dorsal and ventral skin, skeletal muscle and kidney. This effect was found 2 weeks after castration. A long-term study is being presently undertaken.

Animals↗