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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↗

PubMed2001

Behavioural responses of piglets to castration: the effect of piglet age.

It has long been assumed that neonatal animals are less sensitive than older animals to pain, and this reasoning has been used to recommend that routine surgical procedures be performed at an early age. In this study we tested if vocal and other behavioural responses to castration increase with piglet age. Piglets (n=84) from 14 litters were assigned to one of six treatment groups: castration or sham castration at 3, 10 or 17 days of age. During the procedure castrated piglets produced high-frequency calls (>1000Hz) at more than three times the rate of piglets in the sham-castrate group. The rate of low-frequency (<1000Hz) calls was also higher for piglets in the castrate group. The rate of high-frequency calling was lower for the youngest pigs but there was no relationship between age and the effect of treatment for any of the vocal responses measured (i.e. no age by treatment interaction). During the first 2h after castration, castrated piglets spent more time sitting or standing and less time lying. During the subsequent 22h, castrated piglets spent marginally more time at the udder and less time lying down. Older piglets missed more nursings. However, the effect of castration did not vary with the age of the piglet for any measure. We conclude that while the factors affecting both the shams and the castrates (e.g. distress due to restraint) may vary with age, the pain of castration is not affected by age within the range of ages that we tested.

Journal Article↗

PubMed1998

Later onset of apoptosis in the bulbourethral glands after castration compared to that in the seminal vesicles.

Androgens affect many different target organs within the male reproductive tract to stimulate their development and secretory cytodifferentiation, and to maintain structure and function in adulthood. Castration causes regression of these organs via apoptosis. However, not all organs of the reproductive tract are equally sensitive to androgen withdrawal. The effects of castration on the mouse seminal vesicles (SVs) and bulbourethral glands (BUGs) were compared in terms of protein and DNA contents, epithelial apoptosis, and proliferative response of epithelial cells to androgen. Castration induced similar, marked decreases in protein contents in the SV and BUG by 2 days after castration which reached a minimum at 16 days post castration. Both organs underwent a decrease in DNA content, but the kinetics of this decline differed. In the SV, DNA content was significantly decreased by 4 days whereas in the BUG this did not occur until 16 days post castration. By day 16 both organs had regressed to roughly the same degree. The apoptotic index in the epithelium reflected this difference in timing as well. Apoptotic index of the SV epithelium was highest on day 3 after castration and declined thereafter. On the other hand, the apoptotic index in the BUG didn't begin to increase until 7 days after castration and became maximal on day 12. Daily injections of testosterone propionate (TP) from day 8, 16, or 30 after castration all increased epithelial labelling index in the SVs to a similar degree. However, the TP-induced increase in the epithelial labelling index in the BUG beginning on day 8 after castration was considerably less than that in BUGs receiving TP treatment from day 16 or 30 after castration. Thus, the proliferative response of the epithelium depended upon prior apoptosis in the gland, with the timing being delayed in the BUG as compared with the SV. The present results indicate that castration induces epithelial apoptosis and reduction in glandular DNA content considerably later in the BUG than in the SV though reduction in protein content in the BUG fell simultaneously with that in the SV.

Animals↗

PubMed1989

An evaluation of calf castration by intra-testicular injection of a lactic acid solution.

This experiment evaluated intra-testicular injection of a sclerosing drug, lactic acid, for castration of bulls. Its use was compared in 58 Brahman cross calves (50 to 128kg) with the general practice of open surgical castration. Chemical castration appeared to be more painful than surgical castration, though post-operative swelling and pain appeared similar for both methods. Chemical castration took 3 times longer than surgical castration (58 sec v 20 sec; P less than 0.01). Scrotal necrosis occurred in 25% of chemically-castrated calves and appeared due to drug leakage from the testes under the high pressure of injection. Healing time for chemical castrates was approximately twice that for surgical castrates. Five chemically-castrated calves (18%) retained one testis. Though all 5 were rendered sterile, each maintained androgenesis. This led to secondary male behaviour which caused management problems. Castration method did not influence post-operative growth. It is concluded that lactic acid administration is not a suitable alternative to the open surgical technique for castration of Brahman cross calves.

Animals↗

PubMed1989

Castration induces luteinizing hormone (LH) secretion in hypophysectomized pituitary-grafted rats receiving pulsatile LH-releasing hormone infusions.

An in vivo isolated pituitary paradigm was used to examine the extent to which negative feedback actions of testicular hormones are exerted directly at the level of the anterior pituitary gland. Hypophysectomized male rats received single anterior pituitary transplants under the kidney capsule. On the next day each hypophysectomized, graft-bearing (H/G) animal was fitted with a concentric atrial catheter system which allowed for intermittent infusions of LHRH (250 ng/5 min.h) and chronic blood sampling. On the fifth or sixth day of infusions, blood samples were obtained 2 h before sham-castration (n = 6) or castration (n = 5) and at every 2-h interval for 24 h thereafter. For comparison, blood samples were similarly obtained from a group of normal pituitary-intact male rats before and after sham-castration (n = 5) or castration (n = 5). Plasma LH and PRL levels in all animals were determined by RIA. In the H/G sham-castrate rats, LH levels remained constant throughout the 24-h postsurgery period. By contrast, plasma LH concentrations in the H/G castrate rats increased steadily for 18 h, reaching a plateau at levels 2- to 3-fold higher than pretreatment values. The absolute amounts of immunoreactive LH, and the trajectory of the LH rise in the H/G castrates closely resembled those in the normal castrates during the initial 20 h after castration; at subsequent time points, however, these similarities were not apparent, as LH levels in normal castrates continued to rise, while those in H/G castrates did not. PRL levels were not significantly different in H/G rats compared to those in their pituitary-intact counterparts. We conclude from these studies that most of the acute (less than 20 h) effects of castration on LH secretion can be accounted for by pituitary escape from direct negative feedback suppression. At longer times after orchidectomy, however, the continued postcastration rise in LH secretion may increasingly depend upon additional hypothalamic input. It is hypothesized that this added input consists of an acceleration of LHRH pulse frequency.

Animals↗

PubMed1991

Control of gonadotropin secretion in the ovine fetus. III. Effect of castration on serum follicle-stimulating hormone levels during the last trimester of gestation.

Gonadal involvement in fetal FSH regulation was examined by studying FSH levels in 13 female (7 castrate and 6 sham control) and 13 male (8 castrate and 5 sham control) chronically catheterized ovine fetuses operated upon in utero at 106-115 days gestation (term = 147 days). These fetuses had been studied previously for pulsatile LH secretion every 2-7 days over a 2- to 38-day period until fetal delivery or death. From each study day, 3 1-h spaced blood samples (1.5-2.0 ml) were taken for FSH determination by RIA (NIH FSH-S8 standard), and the results were averaged. The overall mean was then calculated for each fetus. In female fetuses, there was no significant difference in mean serum FSH levels between castrates [53.4 +/- 5.0 ng/ml (+/- SEM)] and controls (52.5 +/- 14.4 ng/ml). In contrast, serum FSH levels in the eugonadal males were significantly (P less than 0.001) lower (23.4 +/- 8.0 ng/ml) than those in castrate males (56.9 +/- 7.1 ng/ml, a value comparable to those observed in both female groups). Mean serum FSH levels declined significantly (P less than 0.001) in castrate fetuses of both sexes after 125 days (61.5 +/- 5.6 vs. 42.4 +/- 7.7 ng/ml in females; 64.1 +/- 6.1 vs. 51.5 +/- 8.6 ng/ml in males). In the males, the FSH decline did not reach sham control levels, which remained unchanged with advancing gestation. Moreover, mean serum FSH levels were significantly higher in a group of 4 male fetuses (62.2 +/- 13.7 ng/ml) castrated at 121-130 days gestation compared to values in 3 age-matched sham castrate controls (22.1 +/- 2.6 ng/ml; P less than 0.001). The increment in serum FSH levels in castrate compared to sham castrate male fetuses demonstrates an important role for the fetal testis in FSH regulation from 106 days gestation until term. The lack of a detectable castration effect on the relatively high serum FSH levels in eugonadal females indicates that the fetal ovary does not play a similar role and suggests that in females, FSH is secreted in a functionally castrate mode. The decline in FSH levels after 125 days in castrate fetuses of both sexes may result at least in part from the previously reported coincident rise in circulating levels of feto-placental sex steroids and/or PRL.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1997

Effects of castration on problem behaviors in male dogs with reference to age and duration of behavior.

OBJECTIVE: To determine whether 9 problem behaviors in adult male dogs were affected by castration and to examine the influence of age and duration of problem behavior on behavioral effects of castration. DESIGN: Cohort study. ANIMALS: 57 male dogs > 2 years old at the time of castration that had > or = 1 of the targeted problem behaviors. PROCEDURE: Data were collected by telephone contact with owners to identify dogs that had > or = 1 problem behavior before castration and to estimate the improvement (ie, decrease) in the objectionable behaviors after castration. Problem behaviors of interest included urine marking in the house, mounting, roaming, fear of inanimate stimuli, aggression toward human family members, aggression toward unfamiliar people, aggression toward other dogs in the household, aggression toward unfamiliar dogs, and aggression toward human territorial intruders. RESULTS: Effects of castration on fear of inanimate stimuli or aggression toward unfamiliar people were not significant. For urine marking, mounting, and roaming, castration resulted in an improvement of > or = 50% in > or = 60% of dogs and an improvement of > or = 90% in 25 to 40% of dogs. For remaining behaviors, castration resulted in an improvement of > or = 50% in < 35% of dogs. Significant correlations were not found between the percentage of improvement and age of the dog or duration of the problem behavior at the time of castration. CLINICAL IMPLICATIONS: Castration was most effective in altering objectionable urine making, mounting, and roaming. With various types of aggressive behavior, including aggression toward human family members, castration may be effective in decreasing aggression in some dogs, but fewer than a third can be expected to have marked improvement. Age of the dog or duration of the problem behavior does not have value in predicting whether castration will have a beneficial effect.

Aggression↗

PubMed2000

Influence of castration on the response of the rat vas deferens to fluoxetine.

Antidepressant drugs such as desipramine and fluoxetine increase norepinephrine (NE) contractile response in rat vas deferens by inhibiting neuronal amine uptake. Fluoxetine, unlike other antidepressants, also inhibits calcium fluxes, which results in an inhibition of maximal NE effect. Since the contractile response of the reproductive tract is under the influence of testosterone, the effect of fluoxetine could be modified according to the endocrine status of the animal. In the present study we evaluated the influence of castration and testosterone replacement (1 mg per 100 g body wt.) on the peripheral action of fluoxetine. Castration was followed by a decrease in vas deferens weight and the appearance of spontaneous activity. Testosterone replacement reversed these effects. Concentration-response curves to NE and calcium were obtained in the absence and the presence of fluoxetine in vasa deferentia from normal, castrated and testosterone-treated castrated rats. After castration the effect of fluoxetine on vas deferens contractility was markedly altered. The spontaneous activity that appears after castration was prevented by fluoxetine and the stimulatory effect on NE-induced contractions was not observed. In contrast, the inhibitory action of fluoxetine on maximal NE effect was increased. Testosterone replacement restored vas deferens response to NE in the presence of fluoxetine. Fluoxetine did not modify the binding parameters of [(3)H]prazosin in vasa deferentia from normal or castrated animals. Cocaine shifted the NE concentration-response curve to the left in all groups, suggesting that the changes in fluoxetine effect following castration were not the result of an alteration of the neuronal uptake mechanism. The nitric oxide synthase inhibitor l-NMMA did not modify vas deferens response to NE in castrated animals either in the absence or presence of fluoxetine. An increased sensitivity to the inhibitory effect of fluoxetine was observed in the calcium concentration-response curves in vasa deferentia from castrated rats, an effect that was reversed by testosterone replacement. The results suggest that the alteration in the responsiveness of vasa deferentia from castrated rats to calcium could be responsible for increased sensitivity to the inhibitory effect of fluoxetine. It is concluded that vas deferens contractile response is testosterone dependent and that this behaviour modifies the effect of drugs such as fluoxetine that have dual effect on contractility.

Adrenergic alpha-Antagonists↗

PubMed1984

Pituitary androgen receptors and the resistance of long-term castrated rams to the androgenic control of luteinizing hormone (LH) secretion.

Luteinizing hormone (LH) responses of short-term (24 h) and long-term (6 mo) castrated rams to testosterone replacement therapy were investigated. Testosterone filled Silastic capsules which maintained physiological concentrations of testosterone in blood (approximately 3.2 ng/ml) prevented the post-castration rise in serum LH of short-term castrated rams but failed to effectively reduce the established elevated serum LH levels in long-term castrated rams. The LH response to exogenous LHRH was also suppressed in the short-term castrated rams, whereas the response was increased in direct proportion to basal LH levels in long-term castrates. The possibility that a change in pituitary androgen receptors may explain the resistance of long-term castrates to testosterone feedback was examined. For this purpose, a cytosolic androgen receptor binding assay was developed using tritiated methyltrienolone (R 1881) as the labeled ligand and dextran-charcoal to separate free and protein-bound steroid. Stable, high affinity (Kd = 0.3-1.5 nM), saturable binding of R 1881 was demonstrated in pituitary cytosol from both intact and castrate rams. Relative binding specificities in intact rams, however, suggested partial binding to a progestin-binding component, whereas receptor binding in long-term castrates was androgen specific. For this reason, androgen receptor binding was studied after addition of triamcinolone acetonide to occupy apparent progestin binding sites. We observed no differences in either androgen receptor concentration (4.10 +/- 0.70 versus 3.23 +/- 0.45 fmol/mg protein; Mean +/- SD) nor ligand affinity at 0 degrees C (Kd = 0.66 +/- 0.34 versus 0.40 +/- 0.08 nM) in 6 mo compared to 24-h castrate rams. These data indicate that the inability of androgens to suppress gonadotropin secretion in long-term castrate rams is unlikely to be related to specific changes in pituitary cytosol androgen receptors.

Animals↗

PubMed1994

Some pre- and postjunctional effects of castration in rabbit isolated corpus cavernosum and urethra.

Pre- and postjunctional effects of castration were investigated in isolated corpus cavernosum (CC) and prostatic and preprostatic urethral preparations obtained from rabbits that had been castrated surgically 14 days before investigation. Preparations obtained from untreated animals were used as controls. Castration did not change the relaxing effects of SIN-1 (NO donor) or papaverine in CC preparations contracted by noradrenaline (NA). Electrical field stimulation of CC preparations contracted by NA or endothelin-1 produced frequency-dependent and tetrodotoxin-sensitive relaxations. As compared with controls, the electrically induced relaxations were increased in preparations from castrated animals. Pretreatment with prazosin increased the electrically induced relaxations in CC from untreated rabbits, but had no effect on preparations from castrated animals. In CC preparations incubated with 3H-NA, castration significantly reduced the electrically evoked release of 3H. L-NOARG, an inhibitor of NO synthase, had no effect on 3H-efflux. In prostatic, but not preprostatic, urethral preparations contracted by NA, the relaxant effects of SIN-1 and vasoactive intestinal polypeptide were significantly smaller following castration. Furthermore, castration significantly reduced electrically evoked relaxations in prostatic urethral preparations contracted by NA, while in preprostatic urethra, no such effect was seen. Castration or L-NOARG had no effect on the electrically induced release of 3H-NA in either of the urethral tissues. The results suggest that the hormonal changes caused by castration may modulate the functional effects in vitro of some parts of the urogenital tract. In penile erectile tissue, the relaxations induced by electrical field stimulation are increased, probably for the most part through a decrease in the neuronal release of NA. In prostatic urethra, on the other hand, electrically evoked relaxations are decreased, possibly as a result of an impaired ability of the smooth muscle itself to respond to relaxant agents. In preprostatic urethra, castration has no obvious functional effects. The physiological consequences of these findings in the in vivo situation remain to be established.

Animals↗

PubMed1995

Influences of sex, castration, and androgens on the eumelanin and pheomelanin contents of different feathers in wild mallards.

In mallards the bright nuptial plumage of the drake represents the neutral, sex hormone-independent coloration of the species that both sexes eventually exhibit after castration. We compared the pheo- and eumelanin contents of feathers from the head, breast, flank, and under-tail coverts in five groups of mallards after the post-nuptial molt in summer: intact hens, intact drakes, castrated drakes, castrated drakes injected with testosterone during the spring, and castrated drakes injected with 5 alpha-dihydrotestosterone during the spring. In the head feathers and under-tail coverts, the gonadal hormones of the intact birds and the testosterone injections into castrates significantly reduced the eumelanin content, tended to increase the pheomelanin content, and, thereby, changed the melanin type from eumelanic in the untreated castrates to mixed melanic in the other three groups. The eumelanin contents of the flank feathers did not differ among the groups, but the pheomelanin contents at this site was significantly elevated in the two intact groups and the testosterone-treated compared to the uninjected castrates. Again, the melanin type changed from eumelanic in the castrates to mixed melanic in the other three groups. The high pheomelanin content of the breast feathers in the castrated birds was significantly reduced in the hens, intact drakes, and testosterone-injected castrates with a concomitant tendency for elevated eumelanin contents. At this site, a change occurred from pheomelanic to mixed melanic. 5 alpha-dihydrotestosterone was clearly less effective than testosterone in affecting the melanin contents in castrates and resulted in an intermediate coloration.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

PubMed2006

Inhibitory effects of castration in an orthotopic model of androgen-independent prostate cancer can be mimicked and enhanced by angiogenesis inhibition.

PURPOSE: Today, the most important treatment of advanced prostate cancer is castration; unfortunately, however, the long-term effect of this therapy is insufficient. Recent studies suggest that castration-induced prostate involution could be caused by primary effects in the prostate vasculature; therefore, we examined if antivascular treatments could mimic the effects of castration. EXPERIMENTAL DESIGN: Androgen-independent AT-1 prostate cancer cells were grown inside the ventral prostate in adult rats. Tumor-bearing animals were treated with an inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor signaling, N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine (ZD6474, AstraZeneca, Södertälje, Sweden), and short-term effects (after 3 days) were compared with those induced by castration. RESULTS: Castration caused decreased vascular density in the normal tissue surrounding the tumor and consequently increased tumor hypoxia and apoptosis, and moderately decreased tumor growth. ZD6474 treatment resulted in decreased tumor vascular density accompanied by increased tumor hypoxia, apoptosis, and decreased tumor growth, suggesting that castration and antiangiogenic therapy work through similar mechanisms. Interestingly, castration or ZD6474 alone worked by reducing vascular density in the surrounding normal tissue and ZD6474 also in the tumor. Combined treatment with castration + ZD6474 was more effective than castration and ZD6474 alone in inducing tumor hypoxia, apoptosis, necrosis, and decreasing tumor vascular density. CONCLUSION: These findings show that a drug that targets the vasculature in the tumor and in the surrounding ventral prostate lobe could mimic and even enhance the effects of castration. Our present findings thus suggest that castration + ZD6474 could be a particularly effective way to treat prostate tumors.

Angiogenesis Inhibitors↗

PubMed1989

Diminished role of LHRH in the control of gonadotroph morphology and function in the long-term castrated male rat.

It was found in previous studies that the neurotransmitter control of the secretion of LHRH and LH differs between long-term castrated and ovariectomized rats. One interpretation of these data was that there was a reduced 'positive drive' in the male, and the question was raised 'how do the gonadotrophs of long-term castrated rats maintain a high level of LH secretion?'. In the present series of experiments, evidence for a reduced dependence of the gonadotrophs upon LHRH stimulation is provided. Although sensitivity to native LHRH was not completely lost in long-term castrated rats, two potent LHRH antagonists (D-pyroglu1,D-Phe2,D-Trp3,6)-LHRH and (N-acetyl-3,4-dehydro-Pro,p-fluoro-D-Phe2,D-Trp3,6)-LHRH, were found to inhibit LH secretion in short-term castrated and long-term ovariectomized rats, but not in long-term castrated rats. Neither blockade of axonal transport with colchicine nor immunoneutralization of LHRH with an antiserum against LHRH (both administered 48 h before blood sampling) produced reductions in serum concentrations of LH in long-term castrated rats, although these treatments significantly suppressed LH levels in short-term castrated animals. Chronic (6-day) infusions of the second LHRH antagonist (up to 450 micrograms/day) neither reduced LH secretion nor altered the morphology of the 'castration cells' in the pituitaries of long-term castrated rats. Chronic treatment with testosterone (15 days), however, reversed these parameters to some extent, and when the testosterone treatment was coupled with chronic infusions of the LHRH antagonist, significantly lower serum levels of LH and reductions in the size of the castration cells were observed. These data thus indicate that castration cells may function autonomously, without the need for LHRH, and that testosterone in some way restores the dependency on LHRH and/or the responsiveness to LHRH of these cells.

Animals↗

PubMed2000

Influence of castration and estrogen replacement on sexual behavior of female-oriented, male-oriented, and asexual rams.

An experiment was conducted to determine whether exogenous estradiol-17beta (E2) could restore sexual behavior in castrated rams. The protocol consisted of three sequential 6-wk periods during which rams were studied while 1) intact, 2) bilaterally castrated, or 3) implanted s.c. with two 7.6-cm silastic implants each containing 309+/-16 mg of E2. Rams (classified as female-oriented [FOR, n = 7], male-oriented [MOR, n = 7], or asexual [n = 7]) were subjected to 30-min sexual behavior tests every 2 wk during the ensuing 18 wk. Rams were observed for mounts and ejaculations using two ovariectomized, estrous ewes and two intact males secured in stanchions. Behavioral data were analyzed using the signed rank test, but asexual rams showed no sexual behavior and therefore were not evaluated statistically. Jugular blood was collected prior to castration and at the end of the 18-wk period, and testicular venous (n = 21) and arterial (n = 8) bloods were collected immediately prior to castration. Radioimmunoassay was used to quantify systemic levels of estrone (E1), E2, and testosterone (T) and testicular serum concentrations of oxytocin (OT). Mounting behavior of MOR and FOR declined after castration (P < .05 and P < .10, respectively). Castration reduced the number of ejaculations by FOR (P < .05), but not by MOR (P > .10). Mounting behavior of castrated MOR and FOR was not affected by E2 treatment relative to that observed if castrated only (P > .10). Treatment of asexual rams with E2 did not stimulate sexual behavior in these rams. There were no marked differences (P > .10) among ram groups with regard to serum concentrations of E1, E2, or T prior to castration (overall mean +/- SE, 12.8+/-.7, 7.6+/-.5, and 2,670+/-780 pg/mL, respectively) or any difference (P > .10) in systemic concentration of E1 or E2 among ram groups after rams were implanted with E2 (overall mean +/- SE, 9.7+/-.7 and 9.0 +/-.7 pg/mL, respectively). Serum concentrations of E2 after implantation of the steroid did not differ from those present while rams were intact (P > .10). Testicular venous and arterial serum concentrations of OT were low and did not differ within or between rams. These results suggest that restoration of E2 concentrations to physiological levels in castrated adult rams (regardless of sexual orientation) cannot stimulate or reestablish sexual behaviors to levels observed prior to castration.

Animals↗