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PubMed1977

Inhibition by prolactin of post-castration rise in LH.

Castration of male and female rats resulted in a marked rise in serum LH. The rise in serum LH was partially or completely prevented by injection of prolactin (Prl), by implantation of a small amount of Prl in the median eminence (ME), by grafting 2 anterior pituitaries (APs) underneath the kidney capsule, or by transplantation of a Prl-secreting pituitary tumor underneath the skin. The larger pituitary tumor transplants secreted more Prl and were more effective in reducing LH release than the smaller tumors which secreted less Prl. Suppression of LH release generally was greater during the earlier than in the later phases of the different treatments. The pituitary LH response to synthetic LH-RH was the same in ovariectomized rats with or without pituitary grafts, and the decrease in hypothalamic LH-RH after orchidectomy was prevented by pituitary grafts. These results indicate that Prl can depress LH release after castration and that these effects are mediated via the hypothalamus.

Animals↗
PubMed1977

Pituitary responsiveness to LRF in castrated male hamsters exposed to different photoperiodic conditions.

The effect of various doses of LRF on pituitary LH and FSH release was examined in castrated adult male hamsters with different photoperiodic histories. Gonadotropin (Gn) release in response to LRF was independent of whether the animals had been exposed to a photostimulatory (LD 14:10) or a nonstimulatory (LD 6:18) light cycle for 60 days following castration. The lowest dose that caused a significant increase in serum Gns was 10 ng LRF/100 g b.w. for LH and 50 ng LRF/100 g b.w. for FSH. These results indicate that photoperiod, which is well known to exert major effects on the reproductive system of the golden hamster, does not do so by directly altering the responsiveness of the pituitary gland to hypothalamic Gn-releasing factor.

Animals↗
PubMed1978

Luteinizing hormone response of castrated rabbits to treatment with testosterone propionate and estradiol benzoate.

The effects of sex steroids on luteinizing hormone (LH) secretion in rabbits of both sexes castrated for at least 2 weeks previously were investigated. An intramuscular (i.m.) injection of testosterone propionate (TP) or estradiol benzoate (EB) was given about midway through blood sampling which ranged from 6 to 12 h. LH and steroids were measured by established radioimmunoassay (RIA) procedures. Variable responses were obtained with animals. Castration itself in most instances led to increases in circulating levels of LH which ranged from normal levels to greater than 200 ng/ml with some evidence for episodic variation. EB was more effective than TP in reducing LH levels and inhibiting episodic release.

Animals↗
PubMed1978

The effect of exposure to ether on prolactin secretion and the half-life of endogenous prolactin in normal and castrated male rats.

Normal and castrated male rats implanted with permanent right atrial cannulae were used, and sequential blood samples were taken every 2 min through the cannula. When the rats, both normal and castrated, were exposed to ether for 2 min, the prolactin (Prl) concentration in plasma was immediately and dramatically elevated. During 40 min of continuous ether anesthesia, plasma Prl concentration was not sustained. After the initial 'surge' of Prl secretion, which lasted about 15 min, the concentration returned to normal levels. Following the peak of the Prl 'surge', Prl disappeared from the circulation with a calculated half-life of 7 min (mean value: 6.9 min; confidence interval: 6.3-7.7).

Animals↗
PubMed1981

Differential effects of low serum levels of estradiol-17 beta on hypothalamic LHRH levels and LH secretion in castrated male rats.

In castrated male rats, gonadal steroid treatment raises the medial basal hypothalamic (MBH) LHRH levels and suppresses LH release. We have now examined whether the steroid-induced MBH LHRH response could occur concomitantly with normal pituitary LH secretion. Of the various concentrations tested, serum estradiol-17 beta (E2) levels in the range of 9-16 pg/ml consistently and selectively stimulated the accumulation of LHRH in the MBH after a long latency period of 60-72 h. These low E2 levels did not suppress LH release at any time interval. Serum LH levels and the episodic pattern of LH secretion were similar to those of castrated control rats. It is unlikely that enhanced pituitary sensitivity in E2-treated rats may have compensated for a decrease in LHRH release since the LH response to exogenous LHRH was similar in E2-treated and control rats. These studies show that dissociation of the feedback effects on the MBH LHRH and pituitary gland LH release may be obtained with low serum concentrations of E2 in male rats; low E2 levels stimulate LHRH accumulation in the MBH by mechanisms which may not involve inhibition of LHRH release.

Animals↗
PubMed1985

Castration affects male rat brain opiate receptor content.

We previously reported that saturable stereospecific binding of [3H]-naltrexone in rat brain homogenates prepared from castrated male rats was greater than the corresponding binding in intact animals. We now report that we have replicated these results and that the difficulty of other investigators in observing these differences is due to methodological factors. Specifically, when samples were filtered individually and rapidly, differences between castrated and intact rats were maintained. The increase in binding was also observed when tissues were washed to remove endogenous opioids prior to incubation, when [3H]-naloxone was used as the ligand, and when various antagonists were used as displacers in the radioreceptor assay.

Animals↗
PubMed1984

Effect of sulpiride on the adenohypophysis of castrated male rats. Immunocytochemistry and ultrastructural cytomorphometry.

Previous studies have shown that N-[(1-ethyl-2-pyrrolidinyl)methyl] )-2-methoxy-5-sulfamoylbenzamide (sulpiride), a psychotrophic drug of clinical use, is a potent antidopaminergic agent, and acts on prolactin and gonadotroph secretions. Cytological changes caused by the effects of this drug were studied in castrated male rats treated with daily doses of sulpiride 5 mg/100 g body weight. Animals were sacrificed 2 months after treatment and their hypophyses processed for cytological and immunohistochemical studies. Cytomorphometry was carried out at the ultrastructural level. An immunocytochemical study was performed with peroxidase-labelled antibody to determine PRL, FSH and LH hormones in gland sections. The administration of sulpiride produced a decrease in granules of prolactin cells. Only the Golgi region showed a positive prolactin reaction and the cytomorphometric study indicated an increase of the area occupied by the endoplasmic reticulum and Golgi complex. In gonadotrophs, treatment with sulpiride decreased the vacuolatin caused by castration. The area occupied by the endoplasmic reticulum was smaller, whereas that occupied by secretion granules and lysosomes became larger. It is suggested that sulpiride treatment increased markedly the mammotroph activity and decreased the gonadotroph one, restoring the vacuolation of the endoplasmic reticulum vacuolation to normal.

Animals↗
PubMed1983

Effect of castration on hypothalamic testosterone metabolism in the male rat.

In vitro studies were performed of hypothalamic testosterone (T) metabolism 30 days after castration of adult male rats. No changes were seen in T conversion into dihydrotesterone and estrogens in the castrated rats. Plasma T levels were decreased while plasma estradiol concentrations did not differ from those of intact controls. It was suggested that the hypothalamic T metabolism probably is not androgen dependent.

Animals↗
PubMed2005

Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer.

PURPOSE: To evaluate the antitumor activity and safety of the epothilone B analog, ixabepilone, with or without estramustine phosphate (EMP), in chemotherapy-naive patients with progressive castrate metastatic prostate cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive ixabepilone (35 mg/m(2)) by intravenous infusion every 3 weeks with or without EMP 280 mg orally three times daily on days 1 to 5. RESULTS: Between December 2001 and October 2003, 92 patients were enrolled and randomly assigned to treatment with ixabepilone alone (45 patients) or in combination with EMP (47 patients). Grades 3 and 4 toxicities experienced by more than 5% of patients included neutropenia (22%), fatigue (9%), and neuropathy (13%) on the ixabepilone arm, and neutropenia (29%), febrile neutropenia (9%), fatigue (9%), neuropathy (7%), and thrombosis (6%) on the ixabepilone + EMP arm. Post-treatment declines in prostate-specific antigen of > or = 50% were achieved in 21 of 44 patients (48%; 95% CI, 33% to 64%) on the ixabepilone arm, and 31 of 45 patients (69%; 95% CI, 55% to 82%) on the ixabepilone + EMP arm. In patients with measurable disease, partial responses were observed in eight of 25 patients (32%; 95% CI, 14% to 50%) on the ixabepilone arm, and 11 of 23 (48%; 95% CI, 27% to 68%) on the ixabepilone + EMP arm. Time to prostate-specific antigen progression was 4.4 months (95% CI, 3.1 to 6.9 months) on the ixabepilone-alone arm and 5.2 months (95% CI, 4.5 to 6.8 months) on the combination arm. CONCLUSION: Ixabepilone, with or without estramustine phosphate, is well tolerated and has antitumor activity in patients with castrate metastatic prostate cancer.

Aged↗
PubMed1981

TAT measures of gender identity (castration anxiety) in father-absent males.

DAT stories of 28 father-absent (FA) and 103 father-present (FP) college males were coded for castration anxiety. Relying on Stoller's (1974) use of castration anxiety (CA) as an index of core male gender identity, it was predicted that FA males would have less secure gender identity and higher CA than FP males. The FP subjects were grouped into three subgroups according to ratings of the quality of father-son interaction (positive, neutral and negative). Social class, age, SAT scores and story-length did not discriminate between FAs and FPs. FAs were significantly higher in CA, but there were no significant differences between the three FP subgroups. Age at father-loss did not affect CA, although father-absence through death rather than divorce, separation or desertion was associated with higher CA. Presence of a stepfather, other significant older male, sibling sex or birth-order did not affect CA level of FAs.

Adolescent↗
PubMed1977

Effects of testosterone implants and hypothalamic lesions on luteinizing hormone regulation in the castrated male rat.

The effects of intrahypothalamic and subcutaneous implants of testosterone (T) and those of hypothalamic lesions on resting levels of circulating LH and pituitary responsiveness to exogenous LHRH were studied in castrated male rats to elucidate hypothalamic and pituitary regulation of LH secretion. Two hundred mug implants of testosterone propionate (TP) in the median eminence region suppressed plasma LH titers before evidence of direct inhibition of pituitary function (as indicated by testing with LHRH) was found. Such implants release appreciable amounts of T into the peripheral circulation in the immediate post-operative period, and SC Silastic (constant release) capsules containing T have similar effects. The findings suggest that, regardless of the site of implant, the initial negative feedback inhibition of LH by T is not dependent on direct action at the pituitary levels but rather appears to be a hypothalamic effect. In the days following exposure to hypothalamic or peripheral implantation of T, however, a progressively developing decline in the response to exogenous LHRH was observed. In order to determine whether this effect results from suppression of endogenous LHRH release, the median eminence-arcuate region was destroyed to remove the source of LHRH. In these animals, the suppression of plasma LH was evident on the first day after the lesion, but pituitary responsiveness to LHRH was unaffected until after one week. When Sialastic capsules were implanted SC into lesioned animals, a more rapid (less than 1 week) inhibition of pituitary responsivity ensued. Suprachiasmatic lesions did not affect basal LH secretion or pituitary responses to LHRH. The data provide evidence for a dual feedback action of T on LH in castrated male rats: an initial inhibitory effect presumably due to hypothalamic inhibition (commencing at around 6h after hypothalamic of SC implantation of T), and a subsequent suppression of pituitary responisveness (after one day) presumably due to direct action of T on the pituitary. In addition to these phenomena, findings in rats bearing median eminence-arcurate lesions suggest that the removal of endogenous LHRH by itself leads to an eventual decline in pituitary responsiveness (greater than one week postoperatively).

Animals↗
PubMed1982

Rapid increase of serum FSH levels in castrated male hamsters following transfer from short to long days or exposure to a single long day.

The purpose of this study was to develop an animal model in which a change in the length of the day could induce a rapid alteration in pituitary gonadotropin release. The transfer of castrated male hamsters (castrated for 34 days) that had been maintained on a nonstimulatory LD 6:18 light cycle for 14 weeks to a stimulatory LD 14:10 light regime resulted in a 2-3 fold increase in serum FSH levels within three days. Furthermore, exposure to a single LD 14:10 light cycle also induced a significant increase in serum FSH titers within three days, even though the animals had been returned to LD 6:18. This animal model should prove extremely useful in elucidating the neutral, endocrine and cellular events which mediate the effects of light on reproductive function.

Animals↗
PubMed1975

Influence of adrenalectomy, castration, and light cycle on steroid hydroxylase activity in the adult male rat liver.

The contribution of the adrenals, the testes, and a light/dark cycle to the regulation of hepatic steroid hydroxylases was studied in vitro by measuring transformation rates (nmol/mg protein/min) of dehydroepiandrosterone (DHA). Normal and adrenalectomized male rats were kept in 12 h light:12 h dark (12L:12D) or in constant light (CL) for 1 week. Normal and castrated rats were kept in 12L:12D for 3 weeks. Rats were killed at 4-h intervals over a 36-h period, hepatic microsomal fractions were incubated with [4-14C]DHA, and C-7 and C-16-oxygenated products were quantitated. The overall mean rate of 7alpha-hydroxylation decreased in normal rats exposed to CL. Rates of both 7alpha- and 16alpha-hydroxylation were significantly greater in normal rats than in the respective group of treated rats, except for the 7alpha-hydroxylase in castrated rats. These results indicate that 16alpha-hydroxylase activity is both gonadal- and adrenal-dependent, whereas 7alpha-hydroxylase activity is adrenal-dependent only. Both enzymes are sensitive to light/dark modulations, although a circadian rhythm could not be conclusively established.

Adrenal Glands↗
PubMed1976

Qualitative changes in the pituitary gonadotropins of the male Rhesus monkey following castration.

Characterization of pituitary LH and FSH from intact and castrated male monkeys showed that gonadotropins from intact males are smaller in average apparent molecular size, and disappear from the circulation of test rats more rapidly than hormones from castrated males. Furthermore, intact male monkey LH and FSH are smaller and are cleared from the rat circulation faster than the gonadotropins from intact female monkeys. We conclude that 1) in the rhesus monkey changes in the properties of pituitary LH and FSH resulting from orchidectomy are similar to those which follow ovariectomy, 2) the response to gonadectomy of the male monkey with regard to the molecular properties of FSH is opposite to that of the male rat, and 3) the relationship between the influence of male and female sex hormones on the apparent molecular size of FSH in the monkey is the reverse of that in the rat.

Animals↗
PubMed1984

Leydig cell hypoplasia causing male pseudohermaphroditism: diagnosis 13 years after prepubertal castration.

An 11-yr-old patient with male pseudohermaphroditism who was castrated at nine days of age and raised thereafter as a female was evaluated to determine the cause of abnormal sexual differentiation. Stimulation with ACTH for 8 h revealed no abnormality in the biosynthesis of cortisol or adrenal androgens. The administration of fluoxymesterone (10 mg, orally, daily) for 5 weeks at age 13 yr led to significant decrements in serum levels of sex steroid-binding globulin and T4-binding globulin to a degree similar to that found in 2 normal men, but no change in the basally elevated levels of FSH and LH. LH bioactivity was normal in the rat Leydig cell bioassay. Skin fibroblasts cultured from a labial skin biopsy revealed normal 5 alpha-reductase activity and normal androgen receptors. Reexamination of the original testis specimens by light microscopy failed to reveal Leydig cells. Furthermore, when immunoperoxidase staining for testosterone was performed on the tissue sections, only 30-35 positive cells/10 high power fields were seen. In contrast, examination of testis sections from 4 male infants who died of other causes revealed 94-836 cells/10 high power fields that stained positively for testosterone. Although hCG stimulation testing to confirm Leydig cell hypoplasia could not be done in this patient because of previous castration, this patient demonstrates that the diagnosis can be made without it by the use of immunohistochemical stains and in vivo and in vitro tests to exclude other disorders of androgen biosynthesis or androgen action.

Adrenocorticotropic Hormone↗
PubMed1984

Estrogen stimulates growth hormone and somatomedin-C in castrate and intact female baboons.

To evaluate the effects of physiological concentrations of estrogen on plasma concentrations of somatomedin-C (Sm-C) and GH, 16 chronic castrate female baboons were implanted either with blank Silastic capsules (n = 5) or capsules containing crystalline estradiol (E2; n = 11), which remained in place for 7 days. By day 7, serum E2 levels in treated animals rose into the physiological adult female range (mean +/- SEM, 96 +/- 9.2 pg/ml) and were greater (P less than 0.0005) than those in control animals (27.5 +/- 3.4 pg/ml). Sm-C concentrations rose significantly by day 7 in treated animals compared to those in control animals, whether assayed from unprocessed plasma (96% increase; P less than 0.01), plasma pretreated with glycine-HCl (99% increase; P less than 0.01), or plasma extracted with acid-ethanol (72% increase; P less than 0.02). GH concentrations in these animals were low and were not significantly different in E2-treated and control animals. To evaluate the effects of pharmacological doses of E2 on Sm-C and GH concentrations, six intact adult female baboons were treated with six daily injections of 1 mg E2 benzoate in oil. Serum E2 rose to a mean level of 1669 +/- 320 pg/ml on day 7. The plasma Sm-C concentration by day 7 was significantly higher than the pretreatment value whether assayed in untreated plasma (4.3-fold increase; P less than 0.01), plasma pretreated with glycine-HCl (2-fold increase; P less than 0.01), or plasma extracted with acid-ethanol (1.7-fold increase; P less than 0.01). Mean serum GH concentrations rose significantly from 3.3 ng/ml on day 0 to 23.6 ng/ml by day 7 (P less than 0.02). Evaluation of the chromatographic profile of native baboon plasma suggested a marked increase in [125I]Sm-C binding to plasma proteins after in vivo pharmacological E2 treatment; a broad peak of [125I]Sm-C binding over a size range from that of albumin to gamma-globulin was found. These results indicate that estrogen treatment of castrate or intact female baboons with both physiological and pharmacological doses results in an increase in plasma Sm-C concentrations that, at least in pharmacological doses, are mediated through an increase in GH concentrations. Although pharmacological E2 treatment results in a stimulation of plasma proteins that bind Sm-C, the effects on plasma Sm-C concentrations were found after procedures that diminish interference from circulating binding proteins. These data support the concept that estrogen may play a role in the physiological increase in plasma concentrations of Sm-C associated with normal puberty.

Animals↗
PubMed1983

Osmium-impregnation patterns of the Golgi complex in the epididymal epithelial cells of castrated and testosterone-injected mice.

After prolonged exposure of mouse epididymal epithelial cells to a solution of osmium tetroxide, reduced osmium compounds were detected in the Golgi cisternae and in the cytoplasm adjacent to the Golgi complex. Their appearance changed in time under certain conditions. Eight days after castration each cisterna of the regularly arranged Golgi lamellae fragmented into small vesicles, in which deposits of reduced osmium compound were in reduced amounts or completely absent, but no notable decrease of the fine reduced osmium particles in the cytoplasm adjacent to the Golgi complex occurred. The amount of deposit in the Golgi cisternae in castrated mice recovered to the normal level after the subcutaneous injection of testosterone for two weeks. On the other hand, the osmium particles observed in the cytoplasm adjacent to the Golgi complex during the recovery process of the lamellar structure increased in amount. This study showed that the reduced osmium compounds were of two kinds, and that the deposits contained in the Golgi cisternae were related to secretory products, and might be controlled by hormonal factors, but the fine reduced osmium particles that appeared in the cytoplasm adjacent to the Golgi complex might be regulated by other factors.

Animals↗
PubMed1977

Effect of hypolipidemia on testosterone-stimulated prostatic growth in castrated rats.

Hypolipidemia caused by Simfibrate feeding for 3 weeks reduced responses of weight and nucleic acid contents to testosterone administration in the ventral and dorsolateral prostates of castrated rats. However, the effect of testosterone on the contents of citrate, fructose, zinc and the activity of testosterone 5alpha-reductase in the glands of castrated animals was not modified by Simfibrate feeding.

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