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Differences in the effects of acetylcholine on the vas deferens from normal and castrated rats. A participation of adrenergic mechanisms.

The epididymal portion of the rat vas deferens from normal and castrated rats exhibited clear differences regarding both the threshold and the maximal response to acetylcholine. Alpha adrenoceptor antagonists, hexamethonium and 6-hydroxydopamine diminished the effectiveness of low acetylcholine concentrations on normal and castrated preparations of the epididymal portion of isolated rat vas deferens, but did not influence the maximal response. On the other hand, desipramine enhanced the action of low concentrations of acetylcholine, both in threshold and maximal response; but failed to alter the reactivity to high concentrations of acetylcholine. The results obtained suggest that low doses of acetylcholine may affect the contractile function of the isolated epididymal portion of rat vas deferens by producing a release of norepinephrine from presynaptic sites and acts in a similar fashion on preparations from both normal and castrated animals.

Acetylcholine↗

Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats.

Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further treated with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues.

Animals↗

[Dehydroepiandrosterone inhibits aggressive behavior in castrated male mice].

Group-housed triads of castrated male Mice attack lactating female intruders. We had previously observed that testosterone or oestradiol inhibited this aggressive behavior. The Mouse brain contains relatively large mounts of dehydroepiandrosterone (D), therefore we have investigated the behavioral effect of this steroid. D was inactive in intact males, whereas it markedly inhibited the attack directed by castrated males, when delivered by an osmotic minipump at the dose of 83 micrograms/day. D was also given by daily injections for 15 days in oil solution, the dose of 80 micrograms/day decreased attacks of castrated males below the level of intact controls, the dose of 40 micrograms was partly active, whereas the dose of 20 micrograms was inactive.

Aggression↗

[Effect of testosterone on ethanol oxidation during chronic alcoholism in castrated rats].

It has been shown in non-alcoholized male rats that castration significantly and appreciably raises the level of endogenous ethanol. In chronic alcoholization of castrated and non-castrated rats, the rate of ethanol elimination (REE) is noticeably increased, with testosterone producing no essential effect on the REE. In the liver, alcohol dehydrogenase activity rises insignificantly under the effect of testosterone, whereas aldehyde dehydrogenase activity declines 30--100%.

Alcohol Dehydrogenase↗

[Primary closure of the scrotal wound in the castration of stallions].

A method of castration in stallions is reported on, in which primary closure of the wound caused by castration was attempted. Primary wound-healing occurred in 90 per cent of 110 stallions showing normally descended testicles, whereas this proportion was 97.4 per cent in thirty-eight unilaterally cryptorchid stallions in which the normally descended testicle was removed using the method described. It is concluded that the present method of castration will only be successful when surgery is carried out under strictly aseptic conditions.

Animals↗

Intestinal oxalate uptake in castrated male and female rats: evidence for altered brush border membrane composition.

The intestinal uptake rate of oxalate (mumoles/h/g tissue wt.) in castrated male (CM) rats, CM rats administered estradiol, and female (F) rats was 1.8, 1.4 and 1.3 times higher than that of male rats, whereas castrated female (CF) rats and CF rats administered testosterone absorbed oxalate at a rate similar to F rats, thereby, suggesting that gonadectomy affected intestinal uptake of oxalate only in male rats The intestinal oxalate uptake rate in all the groups increased linearly with increasing oxalate concentration (0.1- 6.0 mM). Chemical composition of brush border membrane showed significant changes in the sialic acid, phospholipid and cholesterol content following castration, which may lead to ultrastructural changes in the membrane thereby, increasing the absorption of oxalate.

Animals↗

[Cytoplasmic and nuclear testosterone receptors in the hypothalamus of androgenized female and castrated male rats].

Receptors for testosterone (T) in the preopticoanterior hypothalamus (PO) and in the arcuate nucleus and median eminence (ARC + ME) were examined in neonatally androgenized female and neonatally castrated male rats. As a result of neonatal castration of males, the concentration of cytoplasmic and nuclear receptors for T in the PO dropped to an undetectable level. In the ARC + ME, the number of T-binding sites in the cytosole fraction remained unchanged, while that in the nuclear fraction decreased 2-fold. In the cytosole fraction of neonatally androgenized females, receptors for T were detectable only in the ARC + ME, the level of binding being not different from that seen in this hypothalamic area in intact and neonatally castrated males. At the same time in the nuclear fraction, receptors for T were detectable in both hypothalamic areas, the number of T-binding sites in the ARC + ME being 1.5 times less than in the PO. The data obtained attest to the involvement of receptors for T in sexual differentiation of the brain and regulation of gonadotropic function of the hypophysis.

Animals↗

[Maturation of gonadotropin function during growth of the male rat: influence of neonatal castration (author's transl)].

Evolution during growth of plasma level gonadotropins, was studied in the normal or castrated rat at birth. In the control animals, the plasma level of gonadotropins increased from the 25th day to the 40th day, then declined to the 90th day. Neonatal castration induced a new phenomenon: the increase of plasma gonadotropins in the normal rat corresponded with a decrease in the castrated animals and inversely. Testis hormones affected gonadotropin function; however, an autonomous maturation of this function, independent of gonadal secretions, appeared to exist.

Aging↗

Suppressive effect of morphine on serum gonadotropin levels in castrated rats.

A single administration of morphine reduced both serum LH and FSH levels in castrated Wistar rats. As the inhibitory effect of morphine on serum LH was antagonized by naloxone, the opiate receptors are involved. Decrease in the serum FSH levels induced by morphine was considerably less than the decrease in serum LH, and naloxone did not significantly reverse this effect of morphine on serum FSH. Increase in the serum LH induced by exogenous LHRH was slightly potentiated and not inhibited by a large dose of morphine, in both intact and castrated rats. Increase in the serum FSH in intact male rats induced by exogenous LHRH was not altered by morphine. In the castrated animals, exogenous LHRH did not further increase the serum FSH levels and the latter was not altered by a concomitant administration of morphine. These results clearly show that the decrease in serum gonadotropin levels by morphine is not due to inhibition of the stimulatory effect of LHRH on the pituitary gland. The mechanism of the differential suppression on serum LH and FSH by morphine is postulated.

Animals↗

Chronic sulpiride treatment produces supersensitivity of striatal adenylate cyclase to dopamine in sexually immature or adult castrated rats.

Sulpiride, a substituted benzamide antipsychotic drug, is considered to be a selective antagonist at dopamine D-2 receptors, largely because it does not inhibit dopamine-stimulated adenylate cyclase activity. It was found that sulpiride in vitro can block dopamine-stimulated adenylate cyclase activity in rat striatum from sexually immature or adult castrated male rats. Chronic treatment with sulpiride (20 mg/kg i.p. twice daily for 15 days) resulted in supersensitivity of dopamine-stimulated adenylate cyclase activity in striatum from sexually immature (3-4 weeks old) as well as adult castrated rats. The apparent Ka was decreased 4-fold in the sulpiride-treated animals, whereas the apparent Vmax remained unchanged. This treatment did not alter dopamine-stimulated adenylate cyclase activity in the striatum from adult male rats. Acute treatment with sulpiride was slightly inhibitory to dopamine-stimulated adenylate cyclase in striatum from the immature rat, suggesting that the supersensitivity after repeated injections could be a compensatory increase. In in vitro studies it was found that sulpiride at nanomolar levels could inhibit the ability of low concentrations of dopamine to stimulate adenylate cyclase activity in striatal particulate fractions from sexually immature or adult castrated rats. Sulpiride did not affect dopamine-stimulated adenylate cyclase in the adult rat striatum. Our results indicate that sulpiride can affect dopamine-stimulated adenylate cyclase activity in animals that are lacking testosterone, or perhaps estrogen. This suggests that sex hormones could regulate the sensitivity and pharmacological profile of dopamine receptors for their ligands.

Adenylyl Cyclases↗

Partial inhibition of castration induced ventral prostate regression with actinomycin D and cycloheximide.

Sprague Dawley male rats were injected subcutaneously with either actinomycin D or cycloheximide in saline immediately after castration. Control animals received saline only. Treatment was repeated daily for 4 subsequent days, and 24 hr after the last injection rats were sacrificed by decapitation. Ventral prostates were dissected and weighed. Actinomycin D and cycloheximide administration significantly reduced the rate of prostatic weight loss in castrated rats; serum testosterone levels in the control and drug treated animals were comparable. Histologic studies of the prostates indicated that drug treated animals had more active epithelial cells than saline injected controls. These results indicate that the rate of prostatic regression induced by castration can be modified by drugs such as actinomycin D and cycloheximide.

Adrenal Cortex Hormones↗

Castration induces a marked reduction in the incidence of thyroid cancers.

Although thyroid disease in humans predominates in females, the prognosis of thyroid cancer in males is much less favorable. To further explore the role of male sex hormones, we utilized the experimental model of radiation-induced follicular cancer in the rat, studying the effects of castration on tumor development. Microscopic evidence of tumor formation was correlated with the biochemical parameters serum thyroxine (T4), thyrotropin (TSH), and thyrocalcitonin (TC) at 24 months. The incidence of follicular carcinomas in intact males ws 58%, compared to 28% in comparable females. Castration of males caused a reduction in the incidence to 22%. Mean circulating levels of TSH were markedly elevated in all three irradiated groups. Mean T4 levels were reduced significantly only in irradiated castrated animals. TC levels were reduced in all irradiated groups. We conclude that although elevated levels of TSH probably play a significant role in the development of radioactive iodine-triggered follicular thyroid neoplasms in the rat, male sex hormone may also play an important role beyond their known effect on basal and thyrotropin-releasing hormone-stimulated TSH.

Adenocarcinoma↗

[Early effect of adrenalectomy and castration on the demethylating activity of the liver microsomal fraction in male rats].

The author examines three indices in liver microsomal fraction during the first five days after castration and adrenalectomy of male rats: demethylation in vitro of amidophen, amount of cytochrome P450 and cytochrome b5. Demethylating activity is lowered significantly to the respective control on the second day after adrenalectomy--73%, on the fifth day--61%; after castration on the third day--71%, on the fifth day--75%; after simultaneous castration and adrenalectomy after two days--53%, but on the fifth day--22%. The amount of cytochrome P450 diminishes parallely to the demethylating activity is due to the reduced amount of cytochrome P450, but the reduction of the latter is explained by the lowered activity of aminolevulanatsynthetase--the limiting enzyme in the synthesis of heme of cytochrome P450. Androgens and corticoids are inductors of microsomal oxidative enzymes and probably on the basis of this action the activity of aminoevulinatsynthetase is affected.

Adrenal Glands↗

Fiber-type effects of castration on the cholinergic receptor population in skeletal muscle.

The effects of castration on the extensor digitorum longus, soleus and levator ani muscles of the adult male rat were examined. After castration, no change was observed in the number of sites or the binding affinity of [125I]-monoiodo-alpha-bungarotoxin to the nicotinic cholinergic receptor population of the slow fiber muscle (soleus). The two fast fiber muscles (extensor and levator) showed no change in binding affinity but a significant change in the number of sites. In these two fast fiber muscles, the number of sites begins to increase within the first few days after castration, peaks at 14 days and begins to decline. The results presented in this report demonstrate three major concepts: 1) influences on skeletal muscle mediated by one receptor population can change the characteristics of another receptor population; 2) at least some androgen effects on skeletal muscle are fiber type specific; and 3) the development of extrajunctional receptors is not solely the function of the nerve-muscle relationship.

Animals↗

Lipids in accessory sex glands of immature, mature and castrated male rats.

The distribution of lipids in accessory sex glands of male rats (immature, adult and castrated) has been analysed. The total lipids and phospholipids in adult rats were maximum in caput epididymis and minimal in prostate. An intermediary picture existed in the cauda epididymis and seminal vesicle. In general, phosphatidyl choline and ethanolamine were the major phospholipids in the tissues. Castration depleted the phospholipids in all the tissues. Glycerides were found to accumulate in caput and cauda epididymis, but were depleted in seminal vesicle and prostate in castrated rats. In immature rats, the total lipids were more than that of adults in caput and cauda epididymis but were less in seminal vesicle and prostate. It is suggested that these discrepancies may be due to the differences in the endogenous titres of hormones, and/or associated with structural and functional specificity of the tissues.

Aging↗

Increase in medial palisade zone dopamine activity after long-term castration in the male rat.

The catecholamine (CA) content was measured in nerve terminals of the median eminence (ME) in normal, castrated and adrenalectomized male rats using quantitative microfluorimetry. CA turnover was determined by rates of CA disappearance after tyrosine hydroxylase inhibition. Noradrenaline (NA) levels and turnover in the subependymal layer (SEL) were unchanged 4 weeks after respective surgeries. Dopamine (DA) levels but not turnover in the lateral palisade zone (LPZ) were increased by castration. DA levels and turnover rates were significantly increased in the medial palisade zone (MPZ) by castration, whereas adrenalectomy selectively decreased MPZ CA levels without affecting the turnover rates. These results were discussed in relation to the concept of a medial and a lateral tuberoinfundibular DA pathway innervating different neuroendocrine structures in the rat ME.

Adrenalectomy↗

Glucocorticoid induction of hepatic alpha2u-globulin synthesis and messenger RNA level in castrated male rats in vivo.

alpha2u-Globulin is a male rat liver protein of Mr = 20,000 which is synthesized in the liver of adult male rats, secreted into the serum, and excreted in the urine. Its function is unknown. The hepatic synthesis of this protein is under complex hormonal control. We had previously shown that castration of male rats diminishes hepatic alpha2u-globulin synthesis and the level of its mRNA, and that administration of androgen to these castrated animals results in the reinduction of the synthesis of this protein and the level of its mRNA. We now report that alpha2u-globulin synthesis and the level of its mRNA can be fully reinduced in castrated males by administration of glucocorticoid alone. This induction is much more rapid than the androgenic induction and is inhibited by the glucocorticoid antagonist progesterone. Administration of glucocorticoid to intact male animals does not induce alpha2u-globulin synthesis above normal levels; however, if alpha2u-globulin synthesis has been depressed in intact male rats by pretreatment with estrogen or cyproterone acetate, the level of this protein can be reinduced by administration of glucocorticoids. The implications for the control of alpha2u-globulin gene expression are discussed.

Animals↗

Sexual behaviour following castration in experienced and inexperienced male rabbits.

Sexual behaviour following castration was studied in rabbits with varying precastrational sexual experience. Although most aspects of sexual behaviour declined within a few weeks of castration, experienced animals of mixed strains continued to mount with unreduced frequency for at least 10 weeks following castration. Inexperienced animals, as well as experienced New Zealand White animals, ceased to ejaculate and mount within 4 weeks. The effect of experience on postcastrational sexual behaviour thus seems to vary between different rabbit strains.

Animals↗