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In vivo patterns of circulating testosterone following castration and intramuscular testosterone propionate injections of adult male rats.

In vivo patterns of circulating testosterone (T) were investigated in castrated and in intact male rats following a single intramuscular injection of 1mg testosterone propionate (TP). In addition, the in vivo clearance pattern of T was investigated following castration. The injection of TP into intact rats resulted in a rapid, statistically significant increase in circulating T which lasted for 12h and returned to normal by 24h post-injection. Circulating T decreased to nondetectable levels by 6h following orchiectomy. Injection of TP into castrated rats caused a rapid increase in circulating T which reached highest levels 60 min after administration. The concentrations of T in TP-treated orchiectomized rats remained elevated for 12h with a gradual decline which persisted for the experimental period of 6 days post-injection and provided moderate maintenance of sex accessory organ weights. TP injections increased circulating T levels in both groups of rats, but the magnitude of elevation was greater in intact animals where the normal T diurnal variations were disturbed. The elevation in circulating T persisted longer in the castrate-TP-treated animals than in intact animals, suggesting a difference in clearance, distribution and metabolism of T in orchiectomized rats.

Animals↗

Effect of castration and gonadal hormones on insulin-induced drinking.

Female Wistar rats in any of the estrual phases have been shown to drink significantly more water than males (p < 0.05), after a single I.P. insulin injection (5 U/kg b.wt.). Sexual differences in insulin-induced drinking persisted after castration when it was made in adult rats (4.6 +/- 1.2 ml/2 h, males = 8; vs. 13.0 +/- 3.1 ml/2 h, females = 8; p < 0.05). On the other hand, when animals were castrated before puberty or when newborn, sexual differences in insulin-induced drinking disappeared. Hence, insulin-induced drinking seems to be a sex-dependent phenomenon that differentiates just before or during puberty since it is abolished by castration prior to sexual maturation. Sex hormone administration in male and female rats castrated at different ages showed a variety of actions on insulin-induced drinking. A pattern emerged showing that androgenized (testosterone treated) rats drank usually less in response to insulin than estrogen-treated rats (independent of their genetic sex). According to the above results, we can conclude that insulin-induced drinking is a phenomenon sensible to gonadal hormones, both by conditioning the differentiation of some physiological structure or mechanisms that underlay drinking behavior in that paradigm and by a direct action on these or other related mechanisms.

Animals↗

Reduction of prostatic binding protein-messenger ribonucleic acid sequences in rat prostate by castration.

Messenger RNA coding for the three subunits of prostatic binding protein was isolated from polysomal RNA of rat ventral prostate by oligo (dT)-cellulose affinity chromatography and purified by repeated sedimentations through sucrose gradients under denaturing conditions. The purified mRNA migrated as a 9S peak in sucrose gradient centrifugation and hybridized with its cDNA within 2 log Rot units. In a cell-free reticulocyte lysate system, the mRNA directed the synthesis of three polypeptides of 12000, 9000, and 8000 daltons. These translation products were identified as the subunits of prostatic binding protein by immunoreaction with antibodies to this protein. Quantitation of prostatic binding protein-mRNA sequences in normal and castrated rats by hybridization with the cDNA probe showed that 3-day castration reduced the prostatic binding protein-mRNA sequences to less than 2% of the normal level. Similar hybridization was performed by using the cDNA to determine the level of prostatic binding protein coding sequences in polysomal poly(A) RNA following castration. The results showed a first-order rate constant of 3.92 X 10-2 h-1 for reduction of prostatic binding protein-mRNA sequences in polysomes. The period of castration required to reduce the level of these sequences to 50% of the normal level was calculated to be 17.6 h.

Androgen-Binding Protein↗

Levels of serum steroids, aromatase activity, and estrogen receptors in preoptic area, hypothalamus, and amygdala of B6D2F1 male house mice that differ in the display of copulatory behavior after castration.

Most male B6D2F1 hybrid house mice continue to copulate after castration (continuers), whereas others do not (noncontinuers). Copulation in continuers appears estrogen dependent. Serum testosterone (T), 17 beta-estradiol (E2), and dihydrotestosterone (DHT), as well as aromatase activity (AA) and estrogen receptor (ER) levels in preoptic area (POA), hypothalamus (HYP), and amygdala (AM) were measured to determine if continuers and noncontinuers differ in estrogen physiology. In general, continuers and noncontinuers did not differ in serum steroid levels, AA, or ER levels. Castration reduced AA in the POA, HYP, and AM. Castration did not affect nuclear ER levels in the POA and HYP but reduced nuclear ER in AM. The data demonstrate that castrated B6D2F1 male mice continue to be under the influence of circulating nongonadal E2 that is important for copulation.

Amygdala↗

Interactive environmental and genetic effects on longevity in the male rat: litter size, exercise, electric shocks and castration.

The effects on longevity of manipulating litter size during rearing and of postweaning forced exercise were observed in intact and castrated male rats. Random-bred sib quintets of newborn littermates were reared in reduced litters or normal litters (5 or 6, or 10-12 young, respectively). The quintets were split into five postweaning treatments: untreated (control), exercised (forced to run by electric shocks), shocked (without exercise), castrated, and castrated and exercised. Reduced litter size increased weaning weight from 46 to 56 g and diminished mean longevity from 724 to 620 days. The decrease in longevity due to reduced litter size was greater in the control (204 days) than in the other postweaning treatments (42 to 142 days). The postweaning treatments affected longevity only in the reduced-litter males; in these, exercise and mere shocks appeared to increase longevity. The variation in longevity among quintets was large and the expression of genetic longevity interacted with the treatments. The regression of individual on mean sib longevity was .89 in the castrates but only .10 in the controls; in exercised and shocked males it was .58 in normal-litter but only .09 in reduced-litter sibs indicating an interaction between pre- and postweaning treatments. The implications of the results on the interpretation of longevity studies are discussed.

Adipose Tissue↗

Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice.

NZB/NZW F1 mice of both sexes were castrated at 2 wk of age and implanted subcutaneously with silastic tubes containing either 5-alpha-dihydrotestosterone or estradiol-17-beta. Mice receiving androgen showed improved survival, reduced anti-nucleic acid antibodies, or less evidence of glomerulonephritis as determined by light, immunofluorescent, and electron microscopy. By contrast, opposite effects were observed in castrated mice receiving estrogen. Intact male NZB/NZW F1 mice received androgen implants at 8 mo, an age when they develop an accelerated autoimmune disease associated with a decline in serum testosterone concentration. Such treated mice had improved survival and reduced concentrations of antibodies to DNA and to polyadenylic acid (Poly A). Prepubertal castration of male NZB/NZW F1 mice results in an earlier appearance of IgG antibodies to Poly A. This effect of castration was prevented if neonatal thymectomy was also performed.

Age Factors↗

Aromatization of testosterone by adipose tissue and sexual behavior of castrated male rats.

The influence of aromatization of testosterone occurring in adipose tissue has been studied in castrated obese male rats. The treatment for 30 days with a subliminal dose (115 micrograms/kg per day) of testosterone propionate improved significantly the sexual performance of castrated obese male rats as compared to the nonobese controls. Untreated castrated obese animals did not show any enhancement of sexual behavior. Furthermore, obesity failed to improve sexual performance in intact male rats. Measurements of plasma levels of testosterone and 17 beta-estradiol showed an increase in aromatization of testosterone in obese rats. Present data suggest that adipose tissue can be considered an important site for aromatization of testosterone to 17 beta-estradiol, and that aromatization is involved in the activation of sexual behavior in castrated male rats.

Adipose Tissue↗

Induction of luteinizing hormone, follicle-stimulating hormone surge in the estrogen-primed castrated male rat by progesterone.

Male rats were castrated at 26 days of age and treated with 0.05, 0.1, 1.0 and 2.0 micrograms/kg of BW of estradiol for 4 days starting with the day of castration. On the morning of Day 30 of life they were sacrificed and serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were determined. A significant reduction of LH and/or FSH occurred only with the 1.0 and 2.0 micrograms/kg of BW dose of estradiol. This was in sharp contrast to results in female rats at the same age in which 0.2 microgram/kg of BW of estradiol suppressed the post-castration rise of gonadotropins. This change in threshold sensitivity to the suppressive effects of estradiol may be one component of the changes accompanying the masculinization of the hypothalamus. The 1.0 and 2.0 micrograms/kg of BW doses of estradiol then were used in combination with 0.1, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg of BW of progesterone. The addition of progesterone to the treatment regimen resulted in either no change or a suppression or stimulation of FSH and LH, depending upon the dose of progesterone used. With the 2 micrograms/kg of BW dose of estradiol, 1.0 mg/kg of BW of progesterone resulted in a surge of both FSH and LH, irrespective of whether it was given in combination with estradiol or a single injection following 4 days of estradiol treatment. This, to our knowledge, is the first demonstration of a gonadotropin surge induced by progesterone in the estrogen-primed castrated male rat.

Animals↗

Effects of castration and estradiol treatment on the postovulatory secretion of follicle-stimulating hormone in the mated rabbit.

The effects of castration on the postovulatory secretion of follicle-stimulating hormone (FSH) was measured in mated rabbits. When ovaries were removed at 12 or 18 h postcoitum, FSH increased within 24 h of surgery but without evidence of the previously observed pattern of FSH secretion in the postovulatory period. To prevent the postcastration rise in FSH, various doses of estradiol were injected into does castrated 12 h after mating. Two micrograms estradiol/kg, given daily, was found to prevent the postcastration rise of FSH but was not sufficient to suppress the postovulatory secretion of FSH in intact animals. The postovulatory pattern of FSH release was disrupted in does castrated at either 12 or 18 h postcoitum despite adequate estradiol replacement therapy. Furthermore, in chronically castrated does treated with estradiol (2 micrograms/kg per day), neither mating nor human chorionic gonadotropin (hCG) injection elicited any change in blood FSH levels even though both treatments have been previously found to cause a postovulatory FSH surge. The results of these studies indicate that the ovary, by way of some ovarian secretion, is required for the postovulatory secretion of FSH in the rabbit. The necessary ovarian factor does not appear to be estradiol.

Animals↗

Effect of castration and testosterone propionate on mouse vibrissae.

Vibrissae of normal mice were measured for six cycles starting at birth. Groups of immature male albino mice were castrated at 21 days of age when E, F, G and H (Danforth nomenclature, 1925) vibrissae were in their first cycle of growth. Levels of testosterone in their peripheral plasma were reduced to about one tenth of the normal. The final length achieved by their vibrissae in all subsequent cycles was shorter than that of normal mice. Another group of immature male mice were treated with implants of testosterone propionate to give plasma levels of approximately five to ten times normal. Their vibrissae showed a significant increase in final length in all growth cycles before and after sexual maturation. Vibrissae of adult male mice treated with excess testosterone showed a significant increase in final length at the end of the growth cycle immediately after commencement of treatment. On the other hand, vibrissae of castrated adult mice showed a significant decrease in final length in the second successive cycle after castration. The rate of growth of all vibrissae remained unchanged. Changes in their final length were brought about by changes in the period of growth. Castrated mice had a slightly longer resting period.

Animals↗

Effect of hormonal steroids on lactate dehydrogenase activity and its isozymes in the coagulating gland of castrated male rats.

The effect of castration and treatment with testosterone propionate, androstenedione and oestradiol-17 beta on the coagulating gland LDH activity and its isozymes were studied. Castration reduced the total LDH activity and administration of testosterone propionate alone was able to restore it back to sham operated control levels. Regarding LDH isozymes, the LDH3 and LDH4 responded very similarly to testosterone and oestradiol. LDH5 was significantly increased only in the androgen treated groups. The post-castration decrease in total M-subunits was restored to sham operated control levels in the testosterone propionate treated group. This was mainly contributed by the LDH3, LDH4 and LDH5 isozymes. The changes observed due to testosterone propionate and androstenedione treatments have been attributed to the rejuvenation of tissue from the castration induced losses. The oestradiol induced events have been associated with the growth of fibro muscular layers observed under similar experimental conditions.

Androstenedione↗

RNA polymerase activities in isolated nuclei of guinea pig seminal vesicle epithelium: influence of castration and androgen administration.

Nuclei from seminal vesicle epithelium of adult guinea pigs were isolated in hypertonic sucrose solution. The incorporation of [3H]UTP by the isolated nuclei into acid-precipitable products was studied. Incorporation required ATP, GTP, CTP, UTP, and Mg+2. It was inhibited by addition of actinomycin D, deoxyribonuclease, or pyrophosphate to the reaction mixture. Thus, incorporation of [3H]UTP by isolated nuclei had the same characteristics that have been demonstrated for the reactions catalyzed by nuclear RNA polymerases. Using alpha-amanitin as a metabolic tool, we established concentrations of (NH4)2SO4. Mg+2, and nucleotides that give maximum assayable activities of nuclear RNA polymerases I and II. When the activities of polymerases I and II were measured in isolated seminal vesicle nuclei of guinea pigs that had been castrated 4 days earlier, a marked decrease in activities was found relative to control values (nuclei from intact animals). No further decrease was found 8 days after castration. Diminished accessibility to the nuclear DNA template and a decrease in the concentration of RNA polymerase molecules seemed to be responsible for the observed effects of castration on activities of RNA polymerases. An increase in ribonuclease activity did not seem to be responsible for the effects of castration. Activities of the enzymes did not change 2, 3, or 4 hours after intraperitoneal injection (2 mg/kg body weight) of each of five different androgens. Similarly, a single intraperitoneal injection of testosterone did not restore enzyme activity of polymerade I or II at any time during the first 24-hour period after hormone administration.

Androgens↗

Fine structural studies on the fate of "castration" cells in the rat adenohypophysis after bilateral oophorectomy.

The fate of castration cells has been studied by electron microscopy after bilateral oophorectomy. The castration cells were characterized by a large-like dilatation of rough endoplasmic reticulum which occupied almost the entire cytoplasm, and first appeared at 5 weeks after operation. Castration cells showed cellular suppression after 15 weeks of the experiment but no degenerative changes were observed at any experimental period. At the later stage of the experiment numerous secretory granules reaccumulated in the cytoplasm of the gonadotrophs and concomitantly lake-like dilatation of rough endoplasmic reticulum in some gonadotrophs gradually decreased and finally disappeared from the cytoplasm. Proportion of the castration cells and mean diameter of the largest cisterane of rough endoplasmic reticulum in each cell attained maximum value at 9 weeks after the operation; thereafter both parameters returned toward normal, although they still remained at a higher level than in controls at 18 weeks after the operation.

Animals↗

Comparison of microvessel densities in rat prostate tissues treated with finasteride, bicalutamide and surgical castration: a preliminary study.

BACKGROUND: A group of anti-androgens with different mechanisms of action and adverse effects have been investigated in patients with gross hematuria related to benign prostate hyperplasia; however, there is not yet any consensus about the standard management of these patients. The present study aims to identify if any one type of the hormonal intervention is superior in terms of the suppression of microvessel formation in the prostate. MATERIALS AND METHODS: A total of 28 mature, healthy male Sprague-Dawley rats (300 +/- 50 g) were used in this study. The rats were randomly assigned to one of four groups (n = 7 per group). The effects of three different hormonal therapies on angiogenesis and microvascularity in rat ventral prostate were compared. Groups 1 and 2 were treated for 28 days with finasteride and bicalutamide, respectively, and rats from Group 3 underwent surgical castration. Following treatment, all rats included in the study underwent dissection of the ventral prostate and immunohistochemical analysis of microvessel density by factor VIII-related antigen. RESULTS: The mean number of microvessels in the finasteride and bicalutamide groups was 24.5 (+/-8.44 SE) and 27 (+/-9.89 SE) respectively. In contrast, the castration and control groups had microvessel numbers of 12.9 (+/-5.35 SE) and 40.3 (+/-5.03 SE) respectively. Differences were statistically significant between all three treatment groups and the controls (P < 0.005); the number of microvessels in rat prostate tissues of the control group was significantly higher than the treatment groups. Mean microvessel densities in the bicalutamide and finasteride groups were significantly higher than microvessel densities in the castration group (P < 0.005). There was no statistically significant difference between mean microvessel number in rat prostate tissue treated with finasteride or bicalutamide (P > 0.05). CONCLUSIONS: Even though finasteride was not as effective as castration in reducing microvessel number, its effect was equal to that of bicalutamide in terms of suppressing the angiogenesis in prostatic tissue. Based on the findings of the present study, finasteride might offer a viable option in the management of macroscopic hematuria by inhibition of microvessel formation within the prostatic tissue. Further clinical studies are warranted.

Androgen Antagonists↗

The effects of castration on neurotransmission in the rat vas deferens.

1 Responses to adrenoceptor agonist drugs and to field stimulation were examined in vasa deferentia from adult castrated or intact rats. Isometric tension was recorded in vitro from whole or transversely bisected vasa. 2 After castration vasa exhibited spontaneous contraction, noradrenaline no longer produced a 'tonic' contraction but increased the 'phasic' spontaneous activity and salbutamol inhibited spontaneous activity by a beta-adrenoceptor-mediated mechanism. 3 After castration the 'adrenergic' components of the contractile responses to field stimulation were lost whereas 'non-adrenergic' responses remained, pre-junctional inhibition of field stimulation-induced contractions by either endogenous or exogenous activation was lost but adrenergic terminals could still be demonstrated microscopically. 4 Testosterone treatment partially reversed these effects of castration. 5 The relevance of these results to the nature of neurotransmission and to the genesis of spontaneous contraction in the vas deferens is discussed.

Adrenergic alpha-Agonists↗

Influence of age, growth, castration and testosterone treatment on the noradrenaline levels of the ductus deferens and the auxiliary male reproductive glands of the rat.

The total amount of noradrenaline (NA) in the male accessories increases with normal growth of the organs and also with the age of the rat. The ductus deferens of the old rat has about twice as high NA concentration as that of the young rat. Castration of the prepuberal rat or the puberal rat leads to retardation or cessation, respectively, of the increase in NA amount of the male genital tract. Only in the old rat does castration produce a definite decrease in NA amount of the tract. Castration always raises the NA concentration of the sex accessories. Testosterone treatment of the puberal rat or the old rat produces minor or no increase, respectively, in total amount of NA of the male sex accessories. Testosterone treatment of old prepuberally castrated rats produces a marked increase in NA content of the male organs. It is concluded that androgens have no substancial direct effect on the adrenergic innervation per se, but affects the transmitter levels of the male organs indirectly through changes in number, size and relative proportion of the target cells of the adrenergic nerves i.e. the smooth muscle cells.

Age Factors↗

Differential susceptibility of male and female mice to encephalomyocarditis virus: effects of castration, adrenalectomy, and the administration of sex hormones.

Male mice have been noted to be more susceptible to encephalomyocarditis (EMC) virus than female animals. Castration of male mice abolished this difference and resulted in enhanced resistance similar to that of female mice. This increase in resistance in castrated males could be eliminated by adrenalectomy. Adrenalectomy alone increased susceptibility in male mice but not in female mice. The administration of a long-acting preparation of testosterone markedly increased susceptibility both in castrated male and female mice, as well as in intact females. Testosterone also had a similar effect in immature mice of both sexes. On the other hand, estradiol, but not progesterone, increased susceptibility to EMC virus in castrated mice of both sexes. These data indicate that testicular, ovarian, and adrenal hormones may influence resistance to EMC virus in the mouse and may be critical determinants of the clinical outcome of infection with this virus.

Adrenal Glands↗

Prepubertal castration alters the phenotypic profile of adult rat thymocytes.

To assess the gonadal influence on the maturation of the thymus, rats were orchidectomized at different periods critical for programming of both gonadal and immune functions, and the composition of the intrathymic thymocyte population was determined in adults by flow cytometric analysis of the surface phenotype. The relative proportion of thymocytes expressing CD4, CD8 and T cell receptor (TCR)alpha beta was measured in the adult rats castrated at 1, 7 and 30 days. Castration performed at postnatal day 1 did not significantly affect expression of these molecules. However, in rats subjected to the surgery at day 7, a significant decrease in the proportion of CD4+CD8+ double-positive cells was found, in parallel with a proportional increase in the percentage of CD4+CD8- single-positive (SP) cells. In rats castrated at age 30 days, in addition to these changes, a small but significant increase in the percentage of CD4-CD8+ SP thymocytes was measured. Castration performed at age 7 and 30 days also caused an enrichment in the thymocyte population expressing TCR alpha beta, probably related to the increase of CD4+CD8- SP cells (7 days) and both CD4+CD8- and CD4-CD8+ SP cells (30 days). The total yield of thymocytes was increased in all experimental groups. We conclude that T cell maturation sequences in the adult thymus are altered if gonadal influence is removed during certain stages of thymus development.

Age Factors↗