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PubMed1984

Serotonin involvement in the inhibition of luteinizing hormone (LH) release during immobilization in castrated male rats.

The involvement of serotonin in mediating the inhibitory effect of immobilization stress on LH secretion in castrated male rats was examined by employing p-chlorophenylalanine (PCPA, 320 mg/kg, ip), an inhibitor of serotonin synthesis, and 5,6-dihydroxytryptamine (5,6-DHT, 50 micrograms, icv), a drug toxic to the indoleaminergic system. Immobilization stress suppressed pulsatile LH release and decreased mean plasma LH levels. Pretreatment with PCPA or 5,6-DHT apparently eliminated the inhibitory effect of immobilization stress on LH release. These results suggest the possible involvement of a serotoninergic mechanism in mediating the suppression of LH release induced by immobilization stress in castrated male rats.

Animals↗
PubMed1993

Increased concentrations of atrial and plasma atrial natriuretic peptide in castrated male rats.

The effects of orchiectomy and testosterone replacement on the plasma concentration and the atrial stores of atrial natriuretic peptide (ANP) were studied in the rats. Male rats were orchiectomized (Orc) three weeks before replacement with testosterone propionate (TP, 20 mg/ml/kg body weight) or sesame oil for five days. Immunoreactive ANP (IR-ANP) in the extracted right atria and plasma of experimental rats was measured. Plasma ANP concentrations were 206 +/- 22, 927 +/- 151, and 264 +/- 61 pg/ml in normal control, Orc, and Orc + TP rats, respectively. ANP contents in right atria were higher in Orc (108 +/- 9 ng/mg tissue) and TP-treated Orc rats (123 +/- 9 ng/mg tissue) than in normal animals (32 +/- 7 ng/mg tissue). These results indicate an increased plasma concentration and atrial stores in the castrated male rats. Replacement of testosterone in the castrated male rats does not decrease the atrial ANP stores, but decreases the plasma ANP concentration.

Animals↗
PubMed1975

Effects of anti-estrogens on testosterone stimulated male sexual behavior and peripheral target tissues in the castrate male rat.

In the first experiment castrated male rats were injected daily with either vehicle or 800 mug testosterone together with either 6 hr pretreatment or concurrent treatment with the anti-estrogens CI-628 (4 mg) or MER-25 (20 mg). The only treatment found to significantly reduce male copulatory behavior was concurrent treatment with CI-628. Anti-estrogen treatment was also found to slightly reduce body weights, increase seminal vesicle weights in response to testosterone and to have no significant effects on androgen stimulated increases in penis weight and length. In the second experiment castrated male rats were injected daily with either vehicle or 500 mug testosterone together with 2.5 mg injections of CI-628 given 6 hr before and concurrent with the androgen injections. The anti-estrogen treatment was found to markedly inhibit the desplay of male sexual behavior, to reduce body weights, and to stimulate seminal vesicle weights. Penile weights and lengths were again not effected by the anti-estrogen therapy. These results were interpreted as supporting the theory that testosterone stimulated male sexual behavior in the rat following its aromatization to estradiol in the brain.

Animals↗
PubMed1975

Post-ejaculatory vocalization in castrated rats treated with various steroids.

Five groups of rats were observed for sexual behavior as intact subjects and in the 3 weeks following castration. Particular emphasis was placed upon ultrasonic vocalization recorded during the refractory period (RP) following ejaculation. All rats received daily injections (100 mug test steroid + 100 mug dihydrotestosterone propionate, DHTP) from the day of castration. Treatment groups were: Testosterone propionate (TP) + DHTP, N = 5; 19-hydroxytestosterone propionate (19HTP) + DHTP, N = 6; Oestradiol dipropionate (OP) + DHTP, N = 5; DHTP (200 mug/day), N = 6; Vehicle only, N = 7. Ejaculation and normal RPs were maintained with TP, 19HTP and OP treatments. In rats treated with DHTP alone or vehicle only ejaculatory ability declined and RPs increased in length. Ultrasonic vocalization was normal in all rats except those treated with OP, where it was either reduced or absent. In Week 4 treatments in TP + DHTP and OP + DHTP groups were reversed. During Weeks 5-7 vocalization was gradually restored in rats that previously received OP and partially inhibited in animals previously treated with TP. These results indicate that; (1) vocalization may not be dependent on the presence of testicular androgens and, (2) OP has a gradual inhibitory effect on vocalization when given at high doses and this effect is reversible.

Animals↗
PubMed1982

Splitting of wheelrunning rhythms by castrated or steroid treated male and female hamsters.

Male and female hamsters, with or without gonadal hormones, were housed in constant light (LL) while wheel running rhythms were recorded. Estradiol benzoate (EB) in Silastic capsules reduced rhythm desynchronies, such as splitting, in ovariectomized animals compared to blank implanted controls. In males, there were no significant effects of testosterone or EB in Silastic implants, castration or sham operation on incidence of rhythm desynchronies. Males generated split rhythms which differed from females in clarity and the angle at which the limbs of the splitting rhythms diverged. Other differences were (a) greater activity onset variability for castrated females with relatively little onset variability for other groups and (b) more running time by EB treated males than any other group. Splitting for all animals occurred with an average latency in LL of 55 +/- 3 days; the period stabilized in 12 +/- 1 days and was 0.2 hr shorter in length. The two limbs of the split rhythm were a mean 181 +/- 5 degrees apart. Induction of splitting by LL is critically discussed with special reference to the two oscillator model of hamster activity and existing evidence for more than two oscillations in wheelrunning activity.

Animals↗
PubMed1975

Androgen binding to cytosol prepared from epididymides of sexually mature castrated rabbits: evidence for a cytoplasmic receptor.

The presence of androgen-binding activity in cytosol prepared from the major anatomical segments (caput, corpus, and cauda) of the epididymis of castrated sexually mature rabbits has been demonstrated. A portion of this binding activity is likely to be the epididymal androgen receptor. When epididymal cytosol from adult castrated rabbits is analyzed on low-ionic strength (0.01 MKCl) sucrose gradients, two peaks of macromolecular binding could be detected, one congruent to 4.6S and one congruent to 8S. On gradients containing 1.0 M KCl, only one sedimenting form congruent to 4.6S could be demonstrated, suggesting that the 8S component is composed of aggregates. If cytosol was preincubated with labeled androgen, followed by an incubation with unlabeled androgen, and subsequently analyzed for binding on low-ionic strength gradients, only the congruent to 8S peak could be detected, indicating that most of the binding in the congruent to 4.6S region was rapidly dissociable. This suggests that binding in this region was to moieties other than receptor. Since androgen binding proteins (ABP) of testicular origin would have been cleared from the epididymis at the timepoints that we concentrated on for most of these studies, the 4.6S binding probably represents the association of androgen with plasma testosterone binding globulin (TeBG). The binding of androgen to the receptor can be inhibited by cyproterone, while this antiandrogen does not inhibit binding to either ABP or TeBG at the concentration used.

Animals↗
PubMedDate not supplied

Maintenance of sexual behavior in castrate male SW mice using the anti-androgen, cyproterone acetate.

The present study was designed to test the hypothesis that cyproterone acetate (C) might selectively block the actions of dihydrotestosterone (D) and via this action, function as an anti-androgen in male sexual behavior. Sexually experienced male SW mice, a strain previously shown to respond to D following castration, were divided randomly into six groups. Beginning on the day after castration, animals received SC injections for 21 days of either testosterone (T), (D), (C), (T+C), (D+C) or vehicle (V). C was found to significantly reduce seminal vesicle and body weights in all androgen treated groups. There was no evidence to support the contention that C selectively blocks the action of D. To the contrary, in sex tests C maintained palpations, thrust mounts, with intromissions and mounts with ejaculations. Indeed, only animals receiving C alone or in combination with T and D exhibited ejaculations throughout the testing. These results suggest that in the SW mouse, C can work like an androgen in the maintenance of male sexual behavior.

Animals↗
PubMed1976

The significance of dopamine, versus other catecholamines, for L-dopa induced facilitation of sexual behavior in the castrated male rat.

The effects of a wide dose range of L-DOPA on male rat sexual behavior were investigated. The animals were castrated as adults and supplied with small amounts of testosterone propionate. It was found that doses of L-DOPA up to 2.5 mg/kg facilitated, while higher doses inhibited, sexual behavior in animals pretreated with pargyline, 20 mg/kg, + MK486, 50 mg/kg. The effects of L-DOPA on sexual behavior were not restricted to the copulatory act, but included elements preceding the copulatory act as well. Most of the facilitatory effects of L-DOPA 2.5 mg/kg were prevented by the dopamine receptor blocker pimozide; 0.10 mg/kg. It is concluded that dopamine is the catecholamine of major importance in mediating the L-DOPA induced facilitation of sexual behavior in the castrated male rat. However, some elements of the copulatory act appear to be modified by noradrenaline and/or adrenaline as well.

Animals↗
PubMed1983

Effects of testosterone metabolites and of anabolic androgens on the bone marrow and thymus in castrated female mice.

Effects of metabolites of testosterone and of anabolic androgens on bone marrow and thymus of ovariectomized mice were studied. Steroids contained in capsules made of silastic tubing were implanted on the day of castration or were injected at the day of castration (Noralone and T.P.), lymphatic organs were examined two weeks later. It was found that testosterone, 5 alpha-DHT, 3 alpha-diol, Dianabole, T.P., and Noralone caused increases in the relative number of large cells and in activity of 20 alpha SDH in bone marrow. Concomitantly, these steroids caused a marked reduction in thymus cell number and an increase in the responsiveness of the thymus cells to Con A and PHA. The steroid 3 beta-diol increased marrow cell 20 alpha SDH activity but did not affect the thymus cell number. Other steroids tested, Ad-dione 3 alpha or 3 beta-androsterone, 5 beta-DHT, epitestosterone, and progesterone had no effect on thymus or bone marrow.

20-Hydroxysteroid Dehydrogenases↗
PubMed1983

Hormonal regulation of sympathetic neuron development. The effects of neonatal castration.

The effects of neonatal castration on neuronal ontogeny were examined in peripheral sympathetic ganglia in male Sprague-Dawley rats. Tyrosine hydroxylase (T-OH) activity, the rate-limiting enzyme in catecholamine biosynthesis and a marker of noradrenergic maturation, was examined in the hypogastric (HG) and superior cervical ganglion (SCG). Initial studies characterized the normal development of T-OH activity in HG ganglia. Neonatal castration at 10-11 days of age prevented the normal ontogeny of HG T-OH activity: T-OH activity failed to develop normally and was 17% of sham-operated littermate controls when examined at 8 weeks of age, and less than 5% when studied 10 weeks after surgery. In contrast to the effects in HG, there was no change in enzyme activity in the SCG. Replacement therapy with testosterone decanoate completely reversed the developmental alteration in enzyme activity. These observations suggest that hormonal factors modulate noradrenergic ontogeny in peripheral sympathetic ganglia but these effects appear restricted to ganglia whose targets include hormonally dependent sex organs.

Animals↗
PubMed1985

Immunological castration by a totally synthetic vaccine: modification of biological properties of LH-RH after conjugation to adjuvant-active muramyl peptide.

Recently, we demonstrated that immunological castration of male mice can be obtained by immunization with Luteinizing Hormone-Releasing Hormone (LH-RH) directly coupled to NAcMur-L-Ala-D-isoGln-L-Lys (MDP-Lys) without carrier and Freund's Complete Adjuvant (FCA) but in the presence of Polyvinyl-Pyrrolidone (PVP). In the present report, we have observed that: (a) immunization by the conjugate, LH-RH-MDP-Lys, was very effective even in absence of PVP, and this conjugate was more active than other conjugates containing MDP coupled to LH-RH fragments; (b) a strong secondary response could be observed by the administration of free LH-RH suggesting that the endogenous secretion of LH-RH might elicit a boosting effect; (c) administration of MDP-Lys coupled to LH-RH decreased the pyrogenicity of the glycopeptide; (d) such a conjugation also decreased the hormonal activity of the antigen although it enhanced its immunogenicity. These results show that a conjugate (2000 dalton) of a decapeptide hormone with a synthetic adjuvant glycopeptide can induce immunological castration in mice after administration in saline. The immunopharmacological properties of the conjugate and its conditions of efficacy suggest that such an approach could find clinical application.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMedDate not supplied

Effects of neonatal administration of monosodium glutamate and castration on neurokinin A levels in the hypothalamus and anterior pituitary of rats.

The effects of neonatal administration of monosodium glutamate (MSG) and castration on hypothalamic and anterior pituitary levels of neurokinin A (NKA) were studied in male and female rats killed at 46 days of age. In male rats treated neonatally with MSG, body, anterior pituitary, testis, ventral prostate, and seminal vesicle weights and serum testosterone levels were significantly lower than in saline-injected controls. Hypothalamic NKA was significantly lower in MSG-treated male rats as compared with the controls, and no apparent changes were recorded in anterior pituitary NKA. Orchidectomy was followed by a significant decrease in hypothalamic NKA in saline controls, but not in MSG-treated rats. In female rats treated with MSG, there was a significant decrease in body, anterior pituitary, and ovarian weights, as compared with saline-injected controls, but no significant differences were observed in uterine weights and serum estradiol levels. Hypothalamic NKA was lower, although not significantly, in MSG-treated rats as compared with the respective controls, and no differences were recorded in anterior pituitary NKA levels. Ovariectomy was followed by a significant decrease in hypothalamic NKA in both MSG-treated and control rats, but NKA in the anterior pituitary was significantly increased after ovariectomy only in saline-treated controls, whereas MSG-treated females failed to show this response. It is concluded that neonatal MSG treatment resulted in a decrease of hypothalamic NKA, which was particularly pronounced in male rats without any significant change in anterior pituitary NKA levels. The response of hypothalamic NKA to castration and the response of anterior pituitary NKA to ovariectomy were also altered in MSG-treated rats; this may reflect a functional block of some neuroendocrine functions of the hypothalamus that resulted from the neuronal lesions induced by MSG.

Animals↗
PubMed1976

Role of the hypophysis in estrogen-mediated induction of enzymes in the regenerating liver from castrated male rats.

Perfusions with corticosterone, of isolated regenerated livers from adult male rats, subjected to castration, partial hepatectomy and hypophysectomy with or without estradiol treatment during parenchymal regeneration, yielded very similar patterns of biliary steroid metabolites. The degree of steroid conjugation was lower than that seen in livers from normal, untreated, adult male rats. In operated animals, with or without estradiol benzoate treatment, ring A-reduced 20-keto metabolites constituted about 20%, whereas metabolites with a 20-hydroxy group made up approximately 80% of the corticosterone metabolites formed. Furthermore, no 15-hydroxylated metabolites derived from corticosterone, quantitatively the most important compounds in bile from female rats, could be detected in bile from these treated male animals. However, livers from male rats which had been castrated, hepatectomized and treated with estradiol benzoate during liver regeneration, produced 15-hydroxy-tetrahydrocorticosterone to the same extent as female rat livers, when perfused with corticosterone. The results obtained indicate that the effects of estradiol on the induction and differentiation of steroid metabolizing enzymes in the regenerating liver are pronounced and manifested only in the presence of an intact hypophysis.

Animals↗
PubMed2004

Excessive testosterone treatment and castration induce reactive astrocytes and fos immunoreactivity in suprachiasmatic nucleus of mice.

The suprachiasmatic nucleus (SCN) has long been recognized as the central mammalian circadian pacemaker that controls behavioral and physiological processes. The role of the SCN in circadian rhythms has been the subject of a wide range of physiological and behavioral studies, although the influence of homeostasis rhythms (such as fluctuating hormone levels) on the SCN of the hypothalamus is not entirely clear. The present study was undertaken to examine the morphological interactions between astroglial and neuronal elements in the SCN of mice after either a short-term excessive testosterone treatment (ETT) or castration, using glial fibrillary acidic protein (GFAP), and immediate early gene c-fos as well as calbindin-D28k (CB) immunohistochemistry. Both ETT and castration resulted in a significant increase in the accumulation of reactive astrocytes and Fos-imunoreactivity (IR), especially in the dorsomedial (DM) sub-region of the SCN. However, CB-IR neurons in the examined brain regions showed little change. These findings indicate that the DM sub-region of the SCN may be a possible center of hormonal regulation via a hypothalamic neuroendocrine circuit, and that a non-photic stimuli mechanism might play a role in circadian rhythm regulation.

Animals↗
PubMed2005

Novel syngeneic pseudo-orthotopic prostate cancer model: vascular, mitotic and apoptotic responses to castration.

We describe a novel syngeneic "pseudo-orthotopic" in vivo model of prostate cancer progression. Our model uses the dorsal skinfold chamber technique with fluorescence video microscopy and TRAMP-C2 tumor cells. The cells were transfected with a histone H2B-GFP fusion protein, permitting real-time measurement of tumor size, as well as mitotic and apoptotic indices. To generate a "pseudo-orthotopic" milieu, pieces of prostate tissue (10-15 mm2) from donor mice were implanted into the chambers of C57BL/6 mice. The prostate tissue grafted into the chambers retained its native vasculature, as determined by transplantation of prostate tissue from GFP transgenic mice. TRAMP-C2 prostate cancer tumor spheroids (25,000 cells) were implanted in the chamber. Without prostate tissue, TRAMP-C2 prostate tumors were poorly angiogenic, displayed low mitotic and apoptotic indices (0.7 x 10(-4)), and no significant tumor growth could be detected. TRAMP-C2 tumors growing on transplanted prostate tissue in the chamber on the other hand had mitotic indices in the order of 1.6 x 10(-4) and apoptotic indices in the order of 0.8 x 10(-4). Furthermore, tumors with stroma were highly angiogenic, and were fully vascularized within 7-10 days. During a 4-week observation period, the number of tumor cells increased by nearly 300%. We used the model to study the effects of surgical castration. The most profound response was a rapid vascular regression of the tumor vasculature. Castration also increased apoptotic indices within the tumor without significant changes in mitosis. This model may be utilized for the rapid analysis of new therapeutic candidates against prostate cancer.

Adenocarcinoma↗
PubMed1976

Effects of adrenalectomy on the sexual behaviour of castrated and intact BDF1 mice.

Two experiments investigate the effects of adrenalectomy on the capacity of male mice of the BDF1 genotype (C57B1/6Fa male X DBA/2 female) to retain sexual behaviour following castration. Adrenalectomy is without effect and it is suggested that androgens can play no part in the maintenance of sexual behaviour in these castrates.

Adrenalectomy↗
PubMed1985

Effectiveness of castration versus intravenous estrogen therapy in producing rapid endocrine control of metastatic cancer of the prostate.

Nine men with histologically confirmed stage D cancer of the prostate were evaluated with serial serum testosterone levels after being treated with bilateral orchiectomy or intravenous estrogen. Bilateral orchiectomy produced castrate serum testosterone levels (less than or equal to 50 ng. per 100 ml.) within 2 to 6 hours (mean 3 hours) after surgery. Intravenous estrogen therapy did not consistently produce castrate serum testosterone levels immediately but did significantly decrease testosterone within 12 hours after infusion. Both forms of therapy are safe, produce a clinically effective response and offer advantages for patients with advanced prostatic cancer.

Adenocarcinoma↗