Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CASTRATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1992

Influences of castration and testosterone on spring to summer changes in release of luteinizing-hormone-releasing hormone in rabbits.

Push-pull cannulae were implanted toward the tuberal region of the hypothalamus in ten intact New Zealand male rabbits. In the first experiment, rabbits were perfused at different times after castration: 5-10 days (n = 10), 22-31 days (n = 9) and 50-64 days (n = 8). The release, mean amplitude and mean frequency of luteinizing-hormone-releasing hormone (LHRH) signals from 37 perfusions in ten animals were analysed in intact rabbits and at different times after castration. No significant changes in release of LHRH and in amplitude were observed, but the frequency was significantly higher 22-31 days after castration than in intact rabbits (intact: 0.86 +/- 0.12; castrated: 1.20 +/- 0.13 pulses h-1, P < 0.035; n = 9). In Expt 2, testosterone and placebo Silastic capsules were implanted in the castrated rabbits. Perfusions were performed in the following four periods, defined by season and time after testosterone and placebo implants: (i) spring; before implants, (ii) late spring; 0-2 weeks after implants, (iii) summer solstice; 2-4 weeks after implants and (iv) summer; 4-6 weeks after implants. Castrated rabbits were perfused during spring; castrated rabbits with testosterone capsule implants were perfused during late spring, around summer solstice and in summer and castrated rabbits with placebo implants were perfused during periods (iii) and (iv). Castrated animals with placebo implants showed no significant changes in mean LHRH release and amplitude, although the frequency was significantly higher around the summer solstice period than in castrated rabbits perfused in the spring. In castrated rabbits with testosterone implants LHRH release was significantly higher in late spring than around the summer solstice and in the summer. In addition, the concentrations of LHRH in late spring were significantly higher than those of intact and castrated animals. In contrast, mean LHRH amplitude and frequency did not change. Mean amount of LHRH released and amplitude in castrated rabbits with testosterone implants were significantly lower around the summer solstice than in late spring or summer and compared with intact animals around summer solstice and in castrated rabbits in early spring. These data demonstrate that there were no significant changes in the mean amplitude and release of LHRH after castration from 5 and up to 64 days in rabbits with hypothalamic push-pull cannulae, in contrast to the well established dramatic effect of castration on gonadotrophin concentrations. However, there was a small, but significant, increase in the mean frequency of LHRH pulses 22-31 days after castration compared with values from intact rabbits.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1996

The effect of castration on steady state levels of luteinizing hormone-releasing hormone (LHRH) mRNA and proLHRH processing: time course study utilizing semi-quantitative reverse transcription/polymerase chain reaction.

Many studies have consistently shown that castration induces a prompt increase in serum levels and pituitary content of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as a concomitant rise in steady state levels of the messenger RNAs directing their synthesis. The reports of effects of castration on the overall physiology of hypothalamic luteinizing hormone-releasing hormone (LHRH)--steady state levels of LHRH mRNA, post-translational processing and secretion--have, however, not been consistent. The goal of the studies reported here was to provide the first analysis of the effect of castration, at multiple postoperative time points, on steady state levels of LHRH mRNA and on the levels of hypothalamic proLHRH. All these data are correlated with hypothalamic levels of the mature LHRH decapeptide and with serum and pituitary levels of immunoreactive LH and FSH. Adult male rats were either castrated or sham-castrated (controls) and then sacrificed at 1, 3, 5, 7, 14, 21 or 28 days postoperatively. As expected, there was a prompt and sustained rise in serum immunoreactive LH and FSH in castrates compared with sham-operated animals. Intra-pituitary LH levels rose above levels in the sham-operated animals by 14 days post castration. Intra-pituitary FSH showed a biphasic response, first falling significantly below control levels, then rising above control levels at 21 days. Steady state levels of LHRH mRNA in castrates, measured by reverse transcription/polymerase chain reaction, were increased about 2-fold above control levels by 1 day postoperatively, but were virtually identical to control levels at each of the other time points despite marked changes in the gonadotropins. ProLHRH content in castrates was 1.8-times that seen in controls at 1 day post castration (P<0.05), concomitant with the rise in steady state levels of LHRH mRNA at that time point. However, proLHRH content in castrates was no different from that seen in controls at each of the later time points examined. LHRH content was unchanged through 7 days after castration, but then fell significantly to 57% of control levels in hypothalami from animals gonadectomized 14 to 21 days previously (P<0.001 vs control), and to 54% of sham-operated levels at 28 days postoperatively (P<0.001). We conclude that: (1) changes in steady state levels of LHRH mRNA after castration are small and transient and (2) increased proLHRH coupled with unchanged LHRH levels at 1 day post castration, and castrate animal proLHRH at control levels coupled with falling LHRH at later post-castration time points indicate that the effect of gonadectomy on post-translational processing of proLHRH to LHRH is, likewise, small and transient. In aggregate our data suggest that most of the increase in serum LH and FSH seen in male rats after castration is not mediated at the hypothalamic level.

Analysis of Variance↗
PubMed1994

The time since castration influences the effects of short-term starvation on gonadotrophin secretion in male rats.

Short-term starvation suppresses the pituitary-testicular function in rats, evidently through inhibition of gonadotrophin-releasing hormone (GnRH) release. However, when gonadotrophin secretion is strongly enhanced, e.g. after castration, starvation does not suppress gonadotrophins. To test whether the time since castration affects the pituitary response to starvation, adult male rats were totally deprived of food for five days (only water allowed) immediately (acute castration) or two weeks after castration (chronic castration). The pituitary contents of GnRH receptors were decreased by starvation in sham-operated animals, unaffected in acutely castrated rats, but increased in chronically castrated animals, in comparison with appropriate controls (P < 0.01). Castration per se increased steady-state mRNA levels of the common alpha-chain and the LH and FSH beta-chains in all groups studied. The only consistent effect of starvation on these parameters was the 1.7 to 2-fold increase in the pituitary content of LH beta-subunit mRNA in acutely and chronically castrated rats (P < 0.01). Starvation alone suppressed LH secretion, acute castration eliminated this effect, but in chronically castrated rats, the starvation effect was stimulatory. Starvation did not affect FSH secretion in sham-operated and acutely castrated rats, but after chronic castration, the effect was stimulatory. In conclusion, the overall effect of starvation on gonadotrophins shifts gradually after castration from suppression, in sham-operated rats, to stimulation, in chronically castrated animals. Parallel changes in pituitary GnRH receptors suggest similar changes in GnRH secretion. Hence, starvation has both negative and positive effects on the GnRH-gonadotrophin-axis. The negative effect is evidently androgen-dependent and dominates in testes-intact animals. After chronic castration, only the positive, non-androgen dependent, stimulatory effect remains.

Animals↗
PubMed1982

Development of tolerance to the effects of morphine on luteinizing hormone secretion as a function of castration in the male rat.

The effects of morphine on the secretion of luteinizing hormone (LH) were examined in male rats at intervals after castration. We found that morphine was extremely effective in suppressing serum LH levels in animals that had been castrated for periods of less than 7 days, but was considerably less potent in long-term castrates (13 + days). For example, the dose of morphine producing the half-maximal suppression of serum LH levels in 3-day castrates was 1.5 mg/kg, whereas in 31-day castrates the ED50 was 13.8 mg/kg. This insensitivity to morphine satisfied the two pharmacological criteria for tolerance: a parallel shift to the right in the morphine dose-response curve and a reduced effect of the drug at the same brain concentration. Hence, castration appeared to render male rats, never exposed to opiates, tolerant to the effects of morphine. Corresponding to the development of tolerance to morphine, 31-day castrates were also less responsive to the LH-depressing effects of testosterone than were 3-day castrates or sham-operated controls. In marked contrast to these results, castration did not significantly affect naloxone-induced increases in serum LH levels. The tolerance observed to morphine in the long-term castrated rat was selective to LH secretion because long- and short-term castrates and sham-operated controls were equally responsive to the antinociceptive effects of morphine (in fact, at a dose of 8 mg/kg long-term castrates were more sensitive to morphine than short-term castrates or sham-operated controls) and there was no apparent shift in the LD50. The mechanisms underlying the development of tolerance to morphine in castrated male rats are not clear at the present time.

Analgesics↗
PubMed2000

Vascular endothelial growth factor-A expression in the rat ventral prostate gland and the early effects of castration.

BACKGROUND: Blood flow to the rat ventral prostate gland is drastically reduced during the very early period after castration, and this reduction coincides with the appearance of striking degenerative changes within the prostatic vascular system. These early effects on the prostate vascular system are likely to be important for the subsequent regression of the ventral prostate that occurs in response to castration. Since the endothelial cells of the ventral prostate do not express androgen receptor protein (AR), we proposed that these early effects might be indirectly mediated by changes in the local expression of vascular regulatory factors. In order to evaluate whether vascular endothelial growth factor-A (VEGF-A) might be among the primary mediators of these effects, we measured expression of VEGF-A mRNA and protein in the rat ventral prostate gland prior to and within the first 3 days after castration. METHODS: Ventral prostate tissues were obtained from control (unoperated) rats, sham-operated rats, or rats at sequential daily intervals (1-3 days) after castration. A quantitative RNase protection assay and a comparative RT-PCR assay were used to evaluate the extent to which the expression of VEGF-A mRNA in the ventral prostate was affected by castration. In situ immunohistochemistry, using an anti-VEGF-A antibody, was performed to localize VEGF-A protein in the various cells of the tissue. Western blot analysis and a quantitative ELISA assay using anti-VEGF-A antibodies were performed to determine how VEGF-A protein expression in the rat ventral prostate was affected by castration. RESULTS: Results of VEGF-A mRNA analysis in the rat ventral prostate gland during the first 3 days after castration showed a biphasic change characterized by a transient reduction of VEGF-A mRNA expression (by approximately 50%) on the second day after castration that was restored to higher than control levels by the third day after castration. Immunohistochemical analysis for VEGF-A in control and castrated ventral prostates showed that the prostatic epithelial and smooth muscle cells were the major source of VEGF-A expression in this tissue. Quantitative analysis of VEGF-A protein expression by Western blot and ELISA methods confirmed a biphasic change in the expression of the polypeptide that correlated well with the results of the mRNA analyses. CONCLUSIONS: VEGF-A expression in the ventral prostate gland of the Sprague-Dawley rat is downregulated on the second day after castration but returns to control levels by the third day after castration. Since critical changes in the ventral prostate vascular system are already evident by 1 day after castration, we believe that these findings indicate that VEGF-A is not likely to be the critical or sole mediator of the early effects of castration on the vascular system of the rat ventral prostate gland.

Androgens↗
PubMed2004

New age eunuchs: motivation and rationale for voluntary castration.

We used a survey posted on the Internet to explore the motivation of men who are interested in being castrated. Out of 134 respondents, 23 (17%) reported already having been castrated. The 104 (78%) individuals who said they had not been castrated were asked why they wanted to be castrated and why they had not actualized that desire. They were given multiple-choice answers to select from. The major reason (selected by 40% of respondents) for desiring castration was to achieve a "eunuch calm" and freedom from sexual urges; however, a large proportion (approximately 30%) of respondents found fantasies about being castrated sexually exciting and a similar percentage desired castration for the "cosmetic" appearance it achieved (which we interpret to mean scrotal removal along with an orchiectomy). This high interest in castration as either a sexual stimulus (a fetish) or a cosmetic enhancement was unexpected and contrasted with the more classically stated motivation for voluntary castration in the psychiatric literature, i.e., libido control and transsexualism. Internet discussion groups that serve these men may encourage them to act out their castration fantasies. Alternately, Internet discussions may give them a displacement outlet for their fantasies and decrease the risk of castration by nonmedically qualified "street-cutters" or by self-mutilation. Forty percent of our respondents claimed that they would have an orchiectomy, if it were cheap, safe, and simple. A quarter wanted to try chemical castration first, but 40% were embarrassed to talk to their doctors about their interest in castration. Information now available on the Internet provides these men with increasingly easy access to street-cutters and directions on how to perform surgical castrations, putting them at risk of permanent injury and disability. Physicians need to be aware of these risks.

Adult↗
PubMed1999

Changes in cyclin dependent kinase inhibitors p21 and p27 during the castration induced regression of the CWR22 model of prostatic adenocarcinoma.

PURPOSE: The expression of the cyclin dependent kinase inhibitors p21 and p27 was examined in prostatic adenocarcinomas following castration. MATERIALS AND METHODS: Male nude mice inoculated with the androgen dependent human prostatic tumor CWR22 were castrated when the tumors reached a volume of 0.8 to 1.1 cm.3 and were sacrificed at 3, 7, 21, 28 and 42 days post-castration. An additional group of mice received a subcutaneous testosterone pellet at 21 days post-castration and was sacrificed at 28 days post-castration. The expression of the Ki-67 antigen, p21 and p27 was examined by immunohistochemistry. RESULTS: The mitotic rate as well as the number of Ki-67 antigen positive cells decreased to 3% of intact control values by 7 days post-castration and were less than 0.01% of intact control values at 21, 28 and 42 days post-castration. The percentage of p21 expressing cells decreased from 15+/-2% in intact controls to less than 1% by 42 days post-castration. In contrast, the percentage of cells that expressed p27 increased from 25+/-3% in intact controls to 51+/-8% at 3 days post-castration and to 80 to 95% at days 7, 21, 28 and 42 days post-castration. Testosterone treatment from 21 to 28 days post-castration resulted in an increase in Ki-67 antigen positive cells to 200% of intact controls and a concomitant reduction in p27 expressing cells to about 50% of intact controls. Castration-induced changes in p27 expression were not observed in the CWR22R tumor, a transplantable relapsed derivative of the CWR22 tumor. CONCLUSION: These findings suggest that p27 expression is regulated negatively by androgens and that increased expression of p27 in CWR22 xenografts may be involved in the suppression of proliferation following castration.

Adenocarcinoma↗
PubMed1987

Biological significance of measurable androgen levels in the rat ventral prostate following castration.

Within 12 hr after castration, there is a dramatic drop in the serum testosterone (T) levels to approximately 1.3% of the intact value (2.5 +/- 0.8 ng/ml). By 1 day following castration, the serum T levels are approximately 3.3% of the intact control level. In contrast, serum 5 alpha-dihydrotestosterone (DHT) levels decrease to only 50% of the intact value within 12 hr postcastration and remain at a value greater than 50% of the intact control level even following long-term castration for up to 20 weeks. Following castration, tissue T and DHT concentrations in rat ventral prostate (RVP) exhibited a similar sequence of changes. Within 12 hr after castration, there is a substantial decrease in T to 27% and DHT to 20% of their intact values; after a further transient decrease during the subsequent 7 days, these levels remain constant with RVP at approximately 40% for T and 20% for DHT of the intact control levels even following long-term castration. Thus castration induces only a partial withdrawal of the tissue androgens. The low but measurable androgen levels in RVP of castrated host are of adrenal origin, since following surgical adrenalectomy these remaining androgen levels become undetectable. Thus castration plus adrenalectomy produces a complete androgen withdrawal within the RVP. To determine the biological significance of the measurable androgen levels remaining following castration, the RVP cell number and the rate of prostatic DNA synthesis were compared in RVP following castration alone (ie, partial androgen withdrawal) or castration combined with surgical adrenalectomy (ie, complete androgen withdrawal). These results demonstrated that complete elimination of the remaining androgens in the RVP of long-term castrates, by means of surgical adrenalectomy, did not induce any further reduction in either of these prostatic growth parameters. Therefore, in the rat, DHT must be decreased to a critical threshold but does not have to be completely eliminated to decrease maximally androgen effect on the prostate.

Adrenal Glands↗
PubMed2000

Acute castration and/or tailing distress and its alleviation in lambs.

PURPOSES AND APPROACH: Acute castration and/or tailing distress in lambs has been examined extensively during the last decade. At least 59 different approaches to assessing and alleviating this distress have been reported so that the literature is quite complex. The purpose of this paper is to provide an overview of the literature on castration and/or tailing distress, where the distress was assessed using acute changes in plasma cortisol concentrations. A method of analysis involving the integrated cortisol response (i.e. the areas under the cortisol curves while the plasma concentration is above pretreatment values) to each treatment and using treatments which were common to different studies as reference points, allowed meaningful comparison within and between studies. A 6-point ranking scale emerged, where rank 1 represented the least distress and rank 6 the most distress. COMPARISON OF ACUTE DISTRESS RESPONSES: This analysis revealed the following major points. Surgical methods of castration and/or tailing cause the greatest cortisol responses (rank 5 or 6). Most ring and ring plus clamp methods of castration plus tailing or castration, used without a local anaesthetic or systemic analgesic, cause rank 4 responses. One form of ring plus clamp castration (i.e. applying the clamp for 10 s across the full width of the scrotum distal to the ring in lambs aged no more than 1 week) reduces the cortisol response to rank 1. When these lambs are also tailed by applying a ring and clamp in a similar manner to the tail, they also exhibit a rank 1 response. Local anaesthetic given 10-20 or 12 min or 10-15 s before or immediately after ring only castration and/or tailing can virtually abolish the cortisol response (rank 1), depending on the site(s) of injection. For ring or ring plus clamp castration, the most effective sites (as judged by cortisol responses) are the neck of the scrotum or the testes. Delivery of local anaesthetic to achieve successful nerve blockade can be by needle, high-pressure needleless administration or, for the tail only, by an aerosol spray. Local anaesthetic injected into the scrotal neck, spermatic cords and/or testes has little effect on the overall cortisol response to clamp castration. Reductions in cortisol responses to clamp castration or to ring tailing can occur after administration of non-steroidal anti-inflammatory drugs. Most tailing methods elicit cortisol responses that are several ranks lower than those caused by castration plus tailing or castration alone. Although tailing by most methods elicits rank 1 cortisol responses, the use of local anaesthetic or non-steroidal anti-inflammatory drugs can reduce the response within the rank 1 range. RECOMMENDATION: Farmers should be encouraged to choose the lowest ranked method that is economically and practically feasible for them. Specific methods such as surgical castration should be discouraged.

Journal Article↗
PubMed1989

Testosterone raises neuropeptide-Y concentration in selected hypothalamic sites and in vitro release from the medial basal hypothalamus of castrated male rats.

Although neuropeptide-Y (NPY)-containing neurons are widely distributed in the hypothalamus, castration decreased NPY concentrations only in the median eminence (ME), arcuate nucleus (ARC), and ventromedial nucleus (VMN). We have now examined the effects of testosterone (T) replacement in 2-week castrated male rats on NPY levels in hypothalamic and preoptic area regions and in vitro NPY release in three experiments. In the first experiment we studied the effect of T on NPY concentration in castrated rats. Two-week castrated rats were implanted sc with T-filled or empty Silastic capsules 30 mm in length. Ten days later rats were killed, and NPY levels were measured by RIA in microdissected sites. T implants raised serum T levels to the range found in gonad-intact rats and decreased serum LH levels to the basal range. Further, of the six brain sites examined, significant increases in NPY concentrations occurred selectively in the ME, ARC, and VMN of T-implanted rats. In the second experiment, the ability of T to reverse the effect of castration on NPY levels compared to those in intact (sham) rats was assessed. Again, castration decreased NPY levels in the ME, ARC, and VMN only, and replacement of physiological levels of T restored NPY levels approximately 100%, 127%, and 74% in the ARC, VMN, and ME, respectively. In the third experiment, the effect of castration and T implants (30-mm T capsules for 10 days) to 2-week castrated rats on the in vitro release of NPY from medial basal hypothalamus (MBH) was assessed. Basal NPY release was not significantly changed after castration and T replacement. However, in response to a 30-min pulse of KCl (45 mM) NPY release from the MBH of castrated rats was significantly reduced compared to that in intact and T-replaced castrated rats. These studies show that castration decreases and T replacement restores NPY levels selectively in three hypothalamic sites, viz. ME, ARC, and VMN, and KCl-induced NPY release from the MBH in vitro is decreased after castration and restored by T replacement, thereby suggesting that a local subset of androgen-concentrating neurons may regulate NPY levels and release in a site-specific manner. Further, these results are in line with our emerging view that gonadal steroids modulate neurosecretion not only of LHRH, but also of other functionally linked regulatory peptides.

Animals↗
PubMed1989

Control of gonadotropin secretion in the ovine fetus. II. A sex difference in pulsatile luteinizing hormone secretion after castration.

Gonadal involvement in the control of fetal LH secretion was examined by studying LH pulsatility in 12 chronically catheterized male (9 castrate and 3 sham-control) and 12 female (8 castrate and 4 sham-control) ovine fetuses operated upon in utero at 106-116 days gestation (term = 147 days). Fetuses were studied longitudinally over a 2- to 30-day period in castrates and over a 2- to 37-day period in controls. LH pulsatility was determined from blood samples obtained every 15 min over a standard 3-h observation period and assayed for LH by RIA (NIH LH S16 standard). In female fetuses there was no significant difference in LH pulse frequency between castrates (25 pulses in 32 periods; 1 pulse/3.8 h of observation) compared to controls (15 pulses in 15 periods; 1 pulse/3.0 h). LH pulse frequency was similar in the sham-castrate males (11 pulses in 17 periods; 1 pulse/4.6 h). In contrast, LH pulse frequency was significantly higher in the castrate male group (90 pulses in 42 periods; 1 pulse/1.4 h) compared to that in each of the other 3 groups (P less than 0.005). LH pulse frequency did not vary with gestational age in castrate and control females or in control males. In castrate males, however, LH pulse frequency declined significantly (P less than 0.005) with advancing gestation from 80 pulses in 32 periods (1 pulse/1.2 h) before 130 days compared to 10 pulses in 10 periods (1 pulse/3.0 h) after 130 days. Thus, LH pulse frequency was indistinguishable in castrate vs. eugonadal males after 130 days. The absence of a castration effect on LH pulsatility in male fetuses older than 130 days was confirmed in an additional group of 8 male fetuses (5 castrate and 3 sham-controls) operated upon at 121-130 days gestation and studied over a 2- to 20-day period. Overall, LH pulse amplitude was similar in male [4.7 +/- 0.5 ng/ml (+/- SE)] and female (3.9 +/- 0.5 ng/ml) fetuses and did not vary as a function of gonadal status or gestational age. The postcastration increment in LH pulse frequency in the castrate male fetus from 108-130 days gestation delineates a role of the fetal testis in feedback regulation of LH secretion at this stage of development. The absence of a postcastration rise in LH pulse frequency in the castrate female indicates that the fetal ovary does not play a similar role.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Hormone ontogeny in the ovine fetus. XXVI. A sex difference in the effect of castration on the hypothalamic-pituitary gonadotropin unit in the ovine fetus.

The detection of pulsatile ovine LH (oLH) secretion in the sheep fetus by 81 days gestation (term 147 days), the suppression of fetal gonadotropin secretion by chronic administration of an LH-releasing factor agonist or antagonist, and the capacity of N-methyl; D-aspartate (a neuroexcitatory amino acid analog) to evoke a fetal oLH pulse strongly support a functional LH-releasing factor pulse-generator in the ovine fetus. In light of the sex difference in fetal gonadal function and gonadotropin secretion before day 114, we postulated that fetal castration would have a discordant effect on the pattern of gonadotropin secretion in males and females. Fetal sheep were either castrated (male = 11; female = 9) or sham operated (male = 9; female = 6) at 110-115 days gestation. Chronic indwelling arterial and venous catheters were implanted, and animals were studied for up to 30 days. During each study period fetal arterial blood samples were drawn every 15 min for 5 h and the plasma assayed for oFSH and oLH by specific RIAs. Multiple studies were performed on each fetus. In all fetuses (both intact and castrated) a decrease in oLH pulse frequency occurred after day 130. In female fetuses before day 130, castration had no effect on mean oLH pulse frequency (sham, 0.72 +/- 0.19 pulses/5 h; castrate, 0.50 +/- 0.13 pulses/5 h; P greater than 0.05). After day 130, pulsatile oLH secretion decreased in both intact and castrated female fetuses to undetectable levels during the sampling period. In contrast, castration significantly (P less than 0.001) increased mean oLH pulsatility in males before and after day 130 (less than 130 days, sham, 1.06 +/- 0.24 pulse/5 h; castrate, 2.70 +/- 0.22 pulse/5 h; greater than 130 days, sham, 0.18 +/- 0.12 pulses/5 h; castrate, 1.65 +/- 0.26 pulses/5 h). Mean oLH pulse amplitude was increased by castration only in the male fetuses (sham, 3.89 +/- 0.87 ng/ml; castrate, 6.02 +/- 0.39 ng/ml; P less than 0.05). oFSH pulses were infrequent in both sexes and not influenced by castration. The mean plasma concentration of oFSH was greater in intact female fetuses than in intact males (female, 5.65 +/- 1.15 ng/ml vs. male, 2.07 +/- 0.45 ng/ml; P less than 0.01). Castration increased the mean value for plasma oFSH in males (4.40 +/- 0.43 ng/ml; P less than 0.001) but had no effect in females (3.83 +/- 0.64 ng/ml; P greater than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1979

Ultrastructure of normals and castrates and the effects of testosterone and ultraviolet (UVL-B) irradiation on scrotal skin of rats.

The ultrastructure of the testosterone dependent epidermal melanocyte system of the scrotal skin of normals and castrates, with and without testosterone replacement therapy, and UVL-B (280-315 nm) radiation in black Long Evans rats is reported. UVL-B increases melanocyte activity, melanosome forming apparatus, (size of Golgi zone and RER, and quantity of cytoplasmic vesicles, dendrites, and stages of melanosomes) in normals and in castrates. Testosterone replacement therapy to castrates is not a prerequisite for stimulation by UVL-B, but it enhances the effects of UVL-B without restoring normalcy as melanosome packaging into complexes predominates. After UVL-B stimulation of normals or castrates, melanocyte dendrites are observed more often. Melanocyte dendrites of skin of castrated rats are observed less often than in normals, but with testosterone replacement therapy, the dendrites become more numerous. Melanosomes donated to keratinocytes are mostly located as singles in normals and as complexes in castrates. After UVL-B, castration, or testosterone replacement therapy, the melanosomes are packaged in keratinocytes in complexes larger than in normals. In the epidermis of long term castrates (9-109 days), non-specific clear cells are observed and Langerhans cells containing melanosomes; we did not observe them in normals. Melanocytes of castrates have a reduced melanosome forming apparatus. The dermis of castrates contains many dermal melanocytes in the superficial dermis with melanosomes in several stages of formation. These cells are not apparent in normals at this location in the dermis. Testosterone replacement therapy and/or UVL-B administered to castrates does not restore the epidermal melanocyte system nor the dermis to precastration ultrastructural appearance; castration has a permanent altering effect as melanosomes are packaged into complexes.

Animals↗
PubMed1984

Studies on the control of gonadotrophin release in the gonadectomized male rat: evidence for a lack of involvement of the hypothalamic noradrenergic system in the long-term castrated rat.

The effects of castration with or without testosterone replacement in the adult male rat were studied to investigate possible hypothalamic mechanisms by which changes in gonadotrophin secretion occur at different times after castration, with particular reference to the continuing LH rise and its lack of suppression by testosterone in the long-term castrated rat. Castrated rats received either subcutaneous silicone elastomer implants containing testosterone or empty implants at the time of castration, and a sham-operated group served as controls. At 1, 10 and 40 days after castration, there were six-, 15- and 25-fold rises respectively in LH and 1.5-, two- and fivefold rises in FSH. However, there were no significant changes in hypothalamic noradrenaline concentration and turnover or in alpha-adrenoceptor density and affinity at any time after castration. Testosterone implants were effective in suppressing gonadotrophin release at 1 and 10 days, but not at 40 days after castration, and did not significantly affect hypothalamic noradrenaline turnover or alpha-adrenoceptors at any time. Neither acute inhibition of the noradrenergic system, using either the alpha-adrenoceptor blockers phenoxybenzamine and phentolamine or the synthesis inhibitor alpha-methyl-p-tyrosine, nor chronic depletion of hypothalamic noradrenaline by 6-hydroxydopamine had any significant effect on the normal rise in LH levels seen on days 10 and 40 after castration, and did not alter the ability of testosterone to suppress LH levels. This indicates that, in the long-term castrated rat, the noradrenergic system may not be involved in the control of gonadotrophin release. However, at 16 h after castration, alpha-adrenoceptor blockers and alpha-methyl-p-tyrosine did reduce LH levels, indicating that the noradrenergic system is likely to be involved in the short-term response to castration.

Adrenergic alpha-Antagonists↗
PubMed1983

[Electron microscopic and morphometric studies of the main kidney segment of male and female rats following castration and testosterone substitution].

The effect of testosterone on the 3 segments of the renal proximal tubule (S1, S2, S3) of male and female rats was studied by electronmicroscopic and morphometric methods. Only light, granulated and dark lysosomes as well as microbodies (peroxisomes) and dictyosomes (Golgi zones) were investigated. After castration the area density of light lysosomes in the S1 segment increases in males whereas it decreases in females; therefore the sex different pattern of light lysosomes, that is to be seen in normal animals, is reversed. The absolute size and number of light giant lysosomes is also elevated in castrated males in comparison to normal animals as well as to animals substituted by testosterone. - Dark lysosomes of the S1 segments are more numerous in castrated females and less numerous in castrated males than in normal animals. - The distinct sex difference in dark lysosomes of the S2 segment which is demonstrable in normal animals disappears after castration the area density of dark lysosomes increasing in castrated females and decreasing in castrated males. The three species of lysosomes in the S1 segments show no longer a sex difference after substitution with testosterone: substituted males develop the same pattern as normal animals and substituted females are almost comparable with normal males. However, the sex difference in dark lysosomes of the S2 segment is more pronounced after testosterone treatment. - The characteristic pattern of light lysosomes in the S1 and S2 segments as well as the change of the sex different lysosomal pattern after castration and substitution with testosterone, respectively - especially in S1 - seem to be caused by testosterone which results in an inhibition of resorption. Only after castration a sex difference appears in dark lysosomes of the S3 segment (males show more dark lysosomes than females). This sex difference is reversed by testosterone treatment. There are more numerous lysosomes with an non-homogeneous matrix in both sexes after castration which are seldom to be seen in normal and substituted animals. The area density of microbodies shows sex differences in all 3 segments of normal animals. While no significant changes in S1 and S2 are to be seen after castration and substitution, there is a pronounced decrease of the area density of microbodies in S3 of males after castration, so that no sex differences are then available.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1996

Effects of castration on plasminogen activator activities and plasminogen activator inhibitor type 1 in the rat ventral prostate.

The involution of the prostate gland after castration is an active process which requires the induction of new proteins. The plasminogen activator urokinase has been proposed to be a gene repressed by androgen which is activated upon castration and thus participating in the atrophy of the gland. However, urokinase is secreted by the ventral lobe of the rat prostate and this should be positively affected by androgens. The purpose of this study was to examine further the effects of castration upon plasminogen activator (PA) activities in the rat prostate and to determine possible explanations to this apparent dilemma. Castration of young sexually mature adult rats resulted in a substantial increase in PA activities at 4 days after castration in the ventral prostate, but then the activities returned to within the range of untreated animals with a longer duration of castration. Urokinase was the predominant molecular form of PA in the normal ventral prostate and it was the molecular form increased after castration; based upon its sensitivity to amiloride and its molecular size determined in zymograms. In contrast to the effect of castration, there was no increase in PA activities in the ventral prostate with treatment of rats with the antiandrogen flutamide, but rather a decrease when specific activity was expressed per unit DNA. In addition, the effect of castration was specific for the ventral lobe for there was no change in the PA activity in the dorsolateral prostate after androgen ablation. The diminished PA activities in the ventral prostates of rats castrated for 7 days or longer appeared to be due at least in part to an increase in plasminogen activator inhibitor type-1 (PAI-1). Immunoreactive PAI-1 was found predominantly in high molecular weight forms which indicates that the inhibitor was complexed with PA. Daily treatment of rats upon castration with agents known to retard the rate of regression of the involuting prostate gave dichotomous results. Hydrocortisone prevented the increase in PA activity, whereas treatment with actinomycin D, an inhibitor of RNA synthesis, not only did not prevent an increase in PA activity, but actually produced a superinduction in PA activity at 4 days orchiectomy. These data may be interpreted to mean that hydrocortisone stimulated PAI activity and that actinomycin D treatment blocked its induction. However, the actinomycin D data may also indicate that an increase in urokinase protein and mRNA after castration may result from some mechanism to conserve these molecules suggesting that this inhibitor of RNA synthesis prevented the transcription of messages for proteins involved in the degradation of urokinase message.

Amiloride↗
PubMed1998

Rapid reduction in blood flow to the rat ventral prostate gland after castration: preliminary evidence that androgens influence prostate size by regulating blood flow to the prostate gland and prostatic endothelial cell survival.

BACKGROUND: Androgenic steroids regulate the development and size of the mammalian prostate gland. The mechanism(s) for this growth control might involve a direct effect on prostate cell proliferation and survival as well as more complex effects on the tissue environment supporting nourishment and oxygenation. In this study, we evaluated an animal model of androgen action on the prostate, the rat ventral prostate gland, to determine whether acute androgen withdrawal, by means of castration, might alter the primary blood flow to the prostate gland and for the effects of castration on prostatic endothelial cell viability. METHODS: Groups of rats studied included intact control males, males that had been surgically castrated, or males that received a sham-surgical castration. Relative blood flow (RBF) to the rat ventral prostate glands and rat bladders were measured at 18 and 24 hr after castration or sham castration using a fluorescent microsphere infusion technique. Thin sections from fixed and embedded rat ventral prostate glands obtained from unoperated or 12-hr castrated rats were analyzed by the TUNEL immunostaining technique to microscopically identify and quantify apoptotic epithelial, stromal, and endothelial cells. RESULTS: RBF to the rat ventral prostate was reduced by 38%, at 18 hr after castration when compared with intact or sham-operated rats and by 45% at 24 hr after castration (P=0.038 unoperated/0.025 sham operated). In contrast, RBF to the bladder was not significantly different between any of the groups in the 24-hr castrate experiment. TUNEL staining analysis of ventral prostate tissues obtained from 12-hr castrated rats showed only rare TUNEL-positive epithelial cells similar to the control tissue but significantly increased TUNEL labeling for endothelial and other ventral prostate stromal cells. CONCLUSIONS: Castration resulted in a rapid and significant reduction of blood flow to the mature rat ventral prostate gland that was not seen in the bladder. This reduction precedes the appearance of apoptosis in the epithelial cells of the tissue but more coincided with the appearance of TUNEL-positive prostate vascular endothelial and stromal cells, suggesting that androgens support the survival of cells in the vascular and stromal compartment of the rat prostate as well as in the prostatic epithelium. These preliminary data support the concept that androgen action on the prostate might involve primary regulation of prostate blood flow and prostate vascular cell vitality.

Androgens↗
PubMed1999

Fas antigen/CD-95 upregulation and activation during castration-induced regression of the rat ventral prostate gland.

BACKGROUND: Fas antigen/CD 95 is a 45-kDa transmembrane protein that can initiate intracellular signaling pathways, leading to apoptosis when it is clustered on the cell surface. A recent report claiming that the ventral prostate glands of lpr -/- mutant mice (lacking functional fas antigen) do not regress following castration prompted our analysis of the regressing rat ventral prostate gland for evidence that fas antigen might participate in the molecular process leading to prostate cell apoptosis after castration. METHODS: An RNase protection assay and Western blotting analysis were used to quantify fas antigen mRNA and protein expression in the regressing rat ventral prostate gland. Immunoprecipitates of fas antigen from membrane preparations made from control or castrated rat prostates were analyzed for coprecipitation of FADD and RIP proteins to assess the activation state of the fas antigen before and after castration. Finally, prostate tissues obtained from two different strains of lpr -/- mutant mice were analyzed for induced apoptosis after castration by the TUNEL staining method. RESULTS: Rat ventral prostate gland fas antigen mRNA and protein expression was upregulated approximately 3-5-fold in the 3-day castrated rat as compared to hormonally intact rats. Immunoprecipitates of fas antigen from membranes of ventral prostates from castrated rats contained significantly increased amounts of both FADD and RIP proteins when compared to those of intact or control operated rats. However, counts of TUNEL-labeled cells in the ventral prostate glands of castrated lpr -/- mice were not significantly different from those in castrated, genetically normal controls. Likewise, the morphology of apoptotic bodies formed in the prostates of castrated lpr -/- mice was indistinguishable from that in control animals. CONCLUSIONS: Fas antigen/CD-95, a protein that is involved in some forms of apoptosis, is upregulated during regression of the rat ventral prostate gland and becomes functionally "activated." However, our inability to distinguish any difference in the apoptosis rate or in the morphology of the apoptotic bodies formed in response to castration between lpr -/- mice and genetically normal controls indicates that, contrary to the prior report, functional fas protein is not required for castration-induced prostate cell apoptosis.

Animals↗