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PubMed1979

Estrogen receptor in the thymus of the castrated mice.

Sucrose density gradient ultracentrifugation and dextran-coated charcoal adsorption permitted us to characterize the estrogen-binding proteins in cytosols obtained from the thymus, spleen and mesenteric lymph node of the castrated male and female mice of C57BL strain. The thymic cytosol from both sexes incubated with 3H-estradiol-17 beta in the presence of excess unlabeled steroids showed a specific estrogenbinding 4 S protein with its binding capacity of 10(-14) moles/mg protein for males and 4 x 10(-15) moles/mg protein for females, respectively. The dissociation constant was of 4 x 10(-10) M for males and 3 x 10(-10) M for females, respectively. No specific binding was, however, found in the cytosols of the spleen and mesenteric lymph node. Steroid analysis by thin-layer chromatography of the thymic cytosols after incubation of them with 3H-estradiol-17 beta showed that a fair amount (around 60%) of radioactivity was from the undegradated radioactive steroid still bound to 4 S binder in both sexes. Enzyme study and heat experiment revealed that the estrogen specific 4 S binding component in the thymic cytosols bears at least protein in nature and is of heat-labile nature. These results strongly suggest that the thymus of the castrated mice contain a specific estrogen receptor, the nature of which is in part protein and heat-labile.

Animals↗
PubMed1987

The intra-acinar distribution patterns of alcohol-dehydrogenase activity in the liver of juvenile, castrated and testosterone-treated rats.

Rat liver alcohol dehydrogenase shows characteristic sex-differences with respect to activity and heterotopy. For the recognition of gonadal influences on the intra-acinar distribution patterns luminometric determinations of ADH activity were carried out on 50-150 ng lyophilized liver tissue samples which had been microdissected along the sinusoidal length. Juvenile rats of both sexes showed equally high alcohol dehydrogenase activity, which surpassed the adult values by a factor of 2 in males and 1.3 in females. The distribution pattern was rather flat, with a weak maximum at the beginning of the last third of the sinusoid. Castration of adult male and female rats resulted in an increase of alcohol dehydrogenase activity to around the prepubertal values. The intra-acinar profiles showed a gradual increase in activity from low periportal values to a peak near the perivenous zone. Only the hepatocytes directly adjacent to the efferent venule showed an even lower activity. Administration of testosterone to castrated animals had no effect on the ADH activity in males and resulted in only a slight decrease of enzyme activity in females. The intra-acinar distribution patterns showed an intermediary peak at the end of the second third of the sinusoidal length in males and a gradual increase of activity, beginning periportally, in the direction of the perivenous zone in females. The present findings on total activity of ADH and its distribution patterns in the liver are considered to be the result of complex hormonal alterations rather than a specific effect of testosterone.

Age Factors↗
PubMed1975

Androgenic properties and adrenal depressant activity of megestrol acetate observed in castrated male rats.

Megestrol acetate (17alpha-acetoxy-6-dehydro-6-methylprogesterone), a synthetic steroid with high progestational activity, is used in oral contraceptives but also in the treatment of prostatic diseases in man. To investigate whether megestrol acetate has any androgenic properties the growth of the ventral and dorsolateral prostate, the coagulating glands and the seminal vesicles was studied morphologically in castrated rats treated with megestrol acetate and in non-treated castrated rats. The effect of megestrol acetate on the body weight, the levator ani muscle and the adrenals was also studied. Megestrol acetate was administered in daily doses of 0.02 mg, 0.2 mg, 2.0 mg or 20.0 mg for a period of 21 days. Megestrol acetate in the two higher doses retarded growth and gave a low weight for the levator ani muscle at autopsy indicating an anti-anabolic or catabolic action of megestrol acetate in high doses. Megestrol acetate in daily doses of 0.2, 2.0 and 20.0 mg caused an involution of the adrenal glands. After the two higher doses the weight of the adrenals amounted to only about a third of that of the untreated rats. Megestrol acetate in the lower doses had no demonstrable effect on the growth of the accessory reproductive glands. After the two higher doses of megestrol acetate some growth of the dorsal part of the dorsolateral prostate and of the coagulating glands was observed. Only the seminal vesicles exhibited complete morphological criteria of an androgenic stimulation and then only after the largest dose of megestrol acetate. The investigation shows that megesterol acetate has weak androgenic properties which are apparent at a dose per kg body weight approximately 200 times greater than that used in the treatment of prostatic diseases in man.

Acetates↗
PubMed1975

5alpha-androstenone in peripheral plasma of pigs, diurnal variation in boars, effects of intravenous HCG administration and castration.

5alpha-Androstenone2) has been measured in pig peripheral plasma by radioimmunoassay (RIA). In 73 mature boars values ranging from 1.2 ng to 54.1 ng per ml plasma with a mean value of 18.3 ng/ml and SD equal to 15.9 were found. In female pigs and castrated male pigs the mean concentrations were 2.3 ng/ml (n equal to 18) and 1.1 ng/ml (n equal to 19) with SD equal to 0.8 and SD equal to 0.3 respectively. Clear-cut diurnal variations in the concentration of 5alpha-androstenone in plasma samples from boars were not observed. Intravenous injection of HCG in boars caused an abrupt rise in the 5alpha-androstenone level reaching a maximum in 90 min. Twenty-eight hours after the injection a second peak of plasma 5alpha-androstenone was observed. Following castration of boars the level of 5alpha-androstenone in peripheral plasma fell within 4 days, to levels found in female pigs.

Androstenes↗
PubMed1975

Measurement of rat LH with a double-antibody solid-phase radioimmunoassay: effect of LH-RH and of testosterone oenanthate in castrated animals.

A double-antibody solid-phase radioimmunoassay for the measurement of rat LH was described. The use of a solid-phase method for the second incubation resulted in a considerable saving of time as compared to the conventional double-antibody method. The sensitivity and accuracy of the method were not affected by this modification. It was found that there was a cross-reaction between the NIAMD-anti-rat-LH-serum-1 used and NIAMD-rat-FSH-RP-1. This indicates that the test system does not specifically measure rat LH but gonadotrophic activity. The RIA was tested under different experimental conditions. In male rats, the effect of castration and of subsequent treatment with testosterone oenanthate upon serum LH, and upon the weight of the seminal vesicles, the ventral prostate, and the levator ani, was examined. Serum LH rose rapidly after castration and reached 2 to 4 weeks after orchidectomy a maximum (8-9 fold increase). Subsequent treatment with testosterone oenanthate caused a rapid decrease of serum LH. The accessory sex organs showed reciprocal changes of weight. In oophorectomized rats whose pituitaries had been blocked with oestradiol monobenzoate and progesterone, a linear log-dose response of plasma LH was found after administration of various doses of synthetic LH-RH.

Animals↗
PubMed1982

Effects of the antioestrogen tamoxifen on steroid induced morphological and biochemical changes in the castrated dog prostate.

The effect of the antioestrogen tamoxifen (TA) was investigated in different types of steroid-induced benign prostatic hyperplasia (BPH) in the castrated dog by histological, histochemical and biochemical analysis. A 6 months treatment with oestradiol-17 beta (E2) alone resulted in cystic and stromal hyperplasia and squamous epithelial metaplasia with a striking prostatic weight increase DNA and RNA content of the total glands increased significantly. The histochemical results and zinc values indicated the loss of normal epithelial function due to metaplatic transformation. The E2 induced cystic and metaplastic hyperplasia was prevented by TA while the stromal proliferation was significantly decreased but not abolished. Biochemical determinations revealed an effect similar to castration. After combined treatment with E2 and 3 alpha-androstanediol (3 alpha-diol) TA completely suppressed squamous metaplasia. A 3 alpha-diol induced glandular proliferation, monitored by a positive histochemical reaction, and significantly elevated zinc, DNA and RNA contents prevailed. A partial stromal stimulation indicates stimulating effects of 3 alpha-diol too on the stroma. The antioestrogenic effects of tamoxifen on experimentally induced BPH mainly manifest at the E2 induced epithelial alterations. The abolishing effects at the stromal level are distinct but not so impressive.

Androstane-3,17-diol↗
PubMed1979

Effects of season on the secretion of LH and testosterone in intact and castrated red deer stags (Cervus elaphus).

At 2--4 monthly intervals during the year blood samples were collected every 15 min for 6 h from 2 intact and 3 castrated red deer stags to study the relationship between season and the secretion of LH and testosterone. In the intact stags plasma LH and testosterone concentrations changed during the year; the LH levels were maximal in August during the phase of testicular redevelopment, while the testosterone levels were maximal from September to November coinciding with the time of peak testicular activity and the mating season. The castrated stags had higher plasma levels of LH than the intact stags at all times of the year, and there was no clear seasonal cycle in LH levels in these animals.

Animals↗
PubMed1979

Effects of castration, 5 alpha-dihydrotestosterone and cyproterone acetate on enzyme activity in the mouse epididymis.

The influence of castration, androgen replacement therapy and cyproterone acetate on the activity of beta-glucuronidase, acid and alkaline phosphatases and glucose-6-phosphate dehydrogenase was studied in the caput, corpus and cauda epididymidis of the mouse. The results add further evidence that the epididymis is not uniform but has regional differences in activity. Thus beta-glucuronidase was found to be androgen-dependent only in the cauda epididymidis, whereas glucose-6-phosphate dehydrogenase was under androgenic control in the caput epididymidis. The response of alkaline and acid phosphatases to castration and to androgen replacement was different in different segments.

Acid Phosphatase↗
PubMed1980

A study of some major testicular steroids in the pig in relation to their effect on the development of male characteristics in the prepubertally castrated boar.

Prepubertally castrated boars received subcutaneous injections twice weekly, from 12 to 38 weeks of age, of testosterone or 5-androstenediol (5-androstene-3 beta,17 beta-eiol) (2 mg/5 kg), or each of these steroids in combination with oestrone (1 mg/5 kg). All steroid treatments induced growth and secretory activity of the accessory organs. The prostate was maintained best by testosterone, and the seminal vesicles by 5-androstenediol. No specific effects of oestrone on these organs were found. Champing of excess saliva was induced in all treated pigs when they were introduced to an oestrous gilt, but only boars receiving testosterone displayed intense mating behaviour including mounting and, in 3 animals, ejaculation; no specific effects of oestrone on behaviour were seen. Low normal levels of unconjugated androgen, and normal to high levels of unconjugated oestrogen were circulating in the treated pigs. There was evidence that peripheral metabolism of exogenous steroids had occurred: 5-androstenediol to testosterone, these two androgens to oestrogen, and sulphation of oestrogen. The sulphate conjugates of dehydroepiandrosterone, 5-androstenediol and oestrone predominated in the peripheral plasma of mature intact boars. Concentrations of 3 alpha-androstenol (5 alpha-androst-16-en-3 alpha-ol) in the submaxillary glands of androgen-treated pigs were similar to those in untreated castrates, thus indicating that androgens are probably not precursors of the pheromonal 16-androstene steroids in vivo.

Androgens↗
PubMed1997

Expression and degradation of rat androgen receptor following castration, testosterone replacement and antiandrogens administration: analysis by Western blot and immunohistochemistry.

To elucidate the autoregulation of androgen receptor (AR) by androgen and antiandrogen, Western blot analysis and immunohistochemical study were performed. Castration reduced the immunodetected AR content, and nuclear staining was lost without cytoplasmic staining. Testosterone (T) supplement restored AR content. Quick response of AR content restoring following single administration of T was observed 48 hours after castration. The recovery of AR content detected by Western blot under each condition was accompanied by recovery of the reduced unclear staining intensities in the epithelia. Neither steroidal nor non-steroidal antiandrogens, chlormadinone acetate and flutamide, altered the AR content in normal rat ventral prostate 5, 12, 24 or 48 hours after single administration. Furthermore, neither of the drugs at various doses altered AR levels 12 hours after single administration. In summary, the rat AR is upregulated by androgen. Single administration of antiandrogens have no effect on immunodetected AR content.

Administration, Oral↗
PubMed1975

Effects of testosterone and prolactin or growth hormone on the accessory sex organs of castrated mice.

In 5-day experiments, neither bovine prolactin (300 or 100 i.u./kg) nor ovine growth hormone (25 i.u./kg) alone significantly enhanced accessory sex organ weights in the castrated mouse. Seminal vesicle weights, and to a lesser extent anterior prostate gland weights, were augmented by the simultaneous injection of testosterone (1-5 mg/kg) daily plus prolactin or growth hormone. The effect was greater than that produced by testosterone alone. The levels of fructose in accessory sex organs used to indicate androgenic activity were similar in castrated mice receiving testosterone alone or in combination with prolactin or growth hormone. Prolactin alone did not influence uptake of (3H)testosterone by the seminal vesicles or anterior prostate gland over a 5 min period in vivo.

Animals↗
PubMed1975

The synergistic action of alpha-melanocyte-stimulating hormone and testosterone of the sebaceous, prostate, preputial, Harderian and lachrymal glands, seminal vesicles and brown adipose tissue in the hypophysectomized-castrated rat.

Alpha-Melanocyte-stimulating hormone was shown to act synergistically with testosterone to stimulate the sebaceous, prostate and the seminal vesicles in hypophys-ectomized-castrated rats. The sebaceous glands differed from the other three organs in that alpha-MSH not only acted synergistically, but also had a significant effect which was independent of the presence of exogenous testosterone. The response of the brown adipose tissue to testerone, considerably reduced by hypophysectomy, was not restored by alpha-MSH. The Harderian and lachrymal glands were also pituitary-dependent and their weights in hypophysectomized-castrated rats were not restored by alpha-MSH.

Adipose Tissue, Brown↗
PubMed1978

Antiandrogenic effects of the pineal gland and melatonin in castrated and intact prepubertal male rats.

In castrated prepubertal rats, pinealectomy enhanced the testosterone-induced growth response of the seminal vesicles and melatonin inhibited this effect in a dose-related manner. In entire animals, the serum concentration of LH was increased after pinealectomy with no significant changes in other parameters. Administration of melatonin to intact, pinealectomized rats did not affect the serum concentrations of LH or testosterone but caused a dose-related decrease in the weight of the seminal vesicles. The highest dose of melatonin tested reduced the weight of the ventral prostate gland and the uptake of radioactivity by both the ventral prostate gland and the testes after injection of [5-3H]uridine. It is suggested that the pineal gland and melatonin may exert an antagonistic effect on the biological activity of androgens administered to castrated rats and that melatonin can reduce the growth of the accessory sex organs of intact, pinealectomized rats, in spite of a high concentration of LH in the serum. The well-known inhibitory influence of systemically administered melatonin on the accessory sex organs in male rats may be due to its antagonistic effect at a peripheral level.

Animals↗
PubMed1980

Synergism between bovine seminal plasma extract and testosterone propionate in suppressing serum concentrations of gonadotrophins in acutely castrated rats: a role for inhibin.

The rise in concentrations of FSH and LH in serum seen 24 h after castration was suppressed by the administration of an extract of bull seminal plasma or testosterone propionate at the time of castration. Whereas testosterone propionate preferentially suppressed LH, the seminal plasma extract suppressed FSH and LH equally. Small doses of bull seminal plasma extract and testosterone, that had little effect separately, acted synergistically to supress levels of FSH and LH to those found in intact animals, while combinations of larger doses had little further effect. This selective interaction suggests how inhibin and testosterone might together regulate concentrations of FSH and LH in the blood of the male rat.

Animals↗
PubMed1983

Concentrations of immunoreactive luteinizing hormone releasing hormone in discrete brain regions of the cockerel: effects of castration and testosterone replacement therapy.

The validity of using a radioimmunoassay employing an antiserum raised against synthetic luteinizing hormone releasing hormone (LH-RH) for the quantification of luteinizing hormone releasing factor (LH-RF) in birds was investigated. Extracts of avian hypothalamus yielded displacement curves which were parallel to that of the synthetic LH-RH standard and the immunoreactive potencies of a number of extracts assayed concurrently using two different anti-LH-RH sera were found to be similar. Moreover, after chromatography of cockerel hypothalamic extract on carboxymethyl-cellulose, immunoreactive and biologically active LH-RF were found in the same eluate fractions. Immunoreactive LH-RH was shown to be widely distributed in cockerel hypothalamus with the highest concentrations present in the mediobasal hypothalamus (MBH; 6.55 +/- 1.86 pg/microgram protein, n = 6) and medial preoptic region (POR; 0.95 +/- 0.07 pg/microgram protein, n = 6). The postcastration rise in plasma LH in the cockerel was accompanied by significant (P less than 0.05) increases in the concentration of LH-RH in five hypothalamic areas including the POR; testosterone replacement therapy completely reversed these effects. Although castration raised the mean concentration of LH-RH in four other hypothalamic areas including the MBH, these differences were not significant. However, testosterone replacement therapy depressed LH-RH in all four regions to levels significantly (P less than 0.05) less than those in castrated cockerels. These findings constitute the first direct evidence that the negative feedback action of testosterone on LH secretion in the cockerel is mediated, at least in part, by an action on hypothalamic LH-RF-producing neurones.

Animals↗
PubMed1985

The passage of 5 alpha-dihydrotestosterone from serum into cerebrospinal fluid and LH negative feedback in castrated rhesus monkeys.

Seven castrated monkeys were given either 50 or 100 micrograms 5 alpha-dihydrotestosterone (DHT) propionate/kg per day. There was no correlation between serum and cerebrospinal fluid (CSF) levels of DHT, which remained very low in the CSF (0.3-0.6% of blood levels) despite the presence of high, supraphysiological amounts in the circulation. There was also no relation between unbound DHT in the blood and the CSF, in which all DHT is unbound. These results differ from previous work on testosterone, the metabolic precursor of DHT. 5 alpha-Dihydrotestosterone propionate at the higher dose maintained suppressed levels of serum LH; LH in two out of four monkeys treated at the lower dose increased to levels observed in castrated, untreated rhesus monkeys. There was no predictable relationship between the amount of DHT in the CSF and levels of LH in the blood: by contrast, DHT in the blood was correlated with serum levels of LH. Levels of LH rose in monkeys in which total blood DHT fell below about 68 nmol/l and, even more obviously, if unbound DHT decreased to less than about 2 nmol/l. Differences between the distribution of testosterone and DHT between blood and CSF cannot be explained by serum binding, lipid solubility or clearance from the brain, and suggest that there may be some mechanism for excluding DHT from the CSF. Though DHT reaches the CSF from the blood in small amounts, levels there do not relate predictably to those in the vascular compartment. It seems unlikely, therefore, that levels of intracerebral DHT are controlled by changes in those of the blood.

Animals↗
PubMed1985

Induction of selective release of FSH in castrated male rats bearing an ovarian transplant by the administration of human chorionic gonadotrophin.

The present study was undertaken to determine whether hypothalamic differentiation is involved in the selective release of FSH during the periovulatory period using adult male rats castrated and implanted with an ovary. Adult male rats (70-90 days old) were castrated and an ovary obtained from a prepubertal female rat (26 days old) was immediately grafted subcutaneously. Four weeks later, human chorionic gonadotrophin (hCG, 10 i.u.) was injected i.v. into the experimentally manipulated rats to induce ovulatory changes in the grafted ovaries. Another group of similarly prepared rats was injected with 0.9% (w/v) NaCl solution as controls. After injection of hCG, plasma concentrations of FSH increased significantly by 6 h, reached peak values at 12 h and declined to control levels at 36 h. On the other hand, plasma concentrations of LH were reduced by 6 h and decreased further during the next 36 h. An abrupt fall in plasma concentrations of oestradiol-17 beta occurred within 3 h of the administration of hCG. Histological examination revealed that ovulatory changes and luteinization of follicles were induced in grafted ovaries by 18 h after the injection of hCG. Thirty-six hours after treatment with hCG, a set of newly formed corpora lutea was observed in grafted ovaries and plasma concentrations of progesterone were raised. Treatment with oestradiol-17 beta did not inhibit the selective release of FSH after the administration of hCG, suggesting that the abrupt decrease in secretion of oestradiol-17 beta from the grafted ovary is not involved in the occurrence of the FSH surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Leptin and ciliary neurotrophic factor enhance the formation of gap junctions between folliculo-stellate cells in castrated male rats.

We investigated the effects of the leptin and ciliary neurotrophic factor (CNTF) on gap junction formation between folliculo-stellate cells in the anterior pituitary glands of male rats. Thirty-day-old Wistar-Imamichi strain male rats were castrated, and 30 days later they received intraperitoneal injections of either human recombinant leptin or recombinant rat CNTF. They were divided into seven groups according to the injected materials: PBS as a control, either 0.04, 0.2 or 1.0 mg/kg leptin or either 0.004, 0.02, or 0.1 mg/kg CNTF. Five rats from each group were killed 1, 2, 3, 4 and 5 days after the injections, and the pituitary gland was removed from each rat. Then the specimens were prepared for observation by transmission electron microscopy. We quantified the number of follicles and gap junctions and calculated the rate of occurrence of gap junctions as the ratio of the number of gap junctions existing between folliculo-stellate cells per intersected follicle profile in electron photomicrographs. The administration of 1.0 mg/kg leptin and 0.1 mg/kg CNTF to castrated male rats increased the number of gap junctions between folliculo-stellate cells. These observations indicate that the formation of gap junctions within the anterior pituitary gland of male rats is under the influence of leptin and CNTF.

Animals↗