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Effects of pinealectomy, anosmia and blinding on serum and pituitary prolactin in intact and castrated male rats.

Serum prolactin was measured in lightly etherized rats between 4 and 5 a.m. and between 11 a.m. and 12 noon at various times after operation in intact rats and rats that had been operated on. Serum prolactin was elevated in the late nocturnal samples from intact rats and this elevation was prevented by pinealectomy. With time following the operation, daytime serum prolactin was also lowered in pinealectomized animals. In animals rendered anosmic by olfactory bulb removal, serum prolactin was also lowered. Superimposed pinealectomy only lowered late nocturnal serum prolactin in anosmic rats. Blinding the rats by ocular enucleation lowered nocturnal serum prolactin initially and dampened the daily rhythm in prolactin, but superimposed pinealectomy had no effect on the blinded animals. The combined sensory deprivation produced by both blinding and olfactory bulb removal resulted in low prolactin titers regardless of whether blood samples were taken during the day or late at night and, as in the case of blinded animals, there was no effect of pinealectomy. Superior cervical ganglionectomy also lowered serum prolactin. Serum prolactin declined following castration in intact animals and this decline was accentuated by pinealectomy. Either blinding or anosmia also lowered serum prolactin in the castrated animals but, as in intact animals, pinealectomy had little effect on the sensory-deprived rats. A further lowering of prolactin occurred in castrated animals which were both blinded and anosmic; in these animals, pinealectomy again had no additional effect. Measurement of the pituitary prolactin content in the castrated animals at sacrifice revealed a significant lowering of values in blinded animals, with restoration of the values to control levels by pinealectomy. Anosmia also lowered the pituitary prolactin content but this was not reversed by pinealectomy. The lowest pituitary prolactin was found in blinded, anosmic animals and these changes were not reversed by pinealectomy. The weight of the pineal gland increased significantly in anosmic, blinded, or blinded and anosmic rats. It is concluded that pineal secretions in the male rat elevate serum prolactin, particularly late at night, and that loss of input from olfactory and to a lesser extent from visual pathways results in a decrease in the titer of the hormone. This decrease is especially apparent in blinded, anosmic rats.

Animals↗

Effects of pinealectomy, anosmia and blinding alone or in combination on gonadotropin secretion and pituitary and target gland weight in intact and castrated male rats.

Pinealectomy had inconstant effects on serum gonadotropins when blood samples were taken during the day, however late nocturanal titers of both FSH and LH tended to decline and this decline tended to be reversed by pinealectomy. Either anosmia or blinding elevated nocturnal FSH and had a tendency to elevate nocturnal LH titers- effects which were only inconstantly modified by pinealectomy. Blinding plus anosmia lowered both daytime and nocturnal FSH titers; the lowering of nocturnal levels was reversed by pinealectomy. There was a less pronounced lowering of nocturnal LH titers in these doubly-operated animals and again this was partially reversed by pinealectomy. These changes in gonadotropin titers probably accounted at least in part for the testicular atrophy seen in the doubly-operated animals and its reversal by pinealectomy. Following castration, plasma gonadotropin titers rose in all groups and the final level of FSH attained was highest in the pinealectomized animals. Similarly, final levels of FSH and LH were further increased in castrates by blinding, anosmia or blinding plus anosmia, but these changes were not consistently modified by pinealectomy. At sacrifice of the castrates, pituitary FSH and LH concentrations were not modified by pinealectomy, however they were elevated by anosmia or by the double sensory-deprivation. The atrophy of the seminal vesicles induced by castration was partially prevented by pinealectomy, which suggests that the pineal also exerts a direct inhibitory effect on this accessory organ. Alterations in anterior and posterior pituitary weight were also observed.

Animals↗

Correlative changes in the response to castration and the onset of refractoriness in male golden hamsters.

This investigation was designed to determine if a correlation exists between a change in the response of the hypothalamo-hypophysial axis to castration and the onset of refractoriness in male hamsters exposed to short days (in this case LD 6:18). The castration response, here defined as a significant increase in serum gonadotropins over levels in intact males, in males exposed to short days for 2 weeks was no different from that observed in long day males. On weeks 4 and 6 the response was greatly attenuated, and on weeks 8 and 10 no castration response was observed. Refractoriness was first observed in a few animals exposed to LD 6:18 for 8 weeks, and in increasing numbers of animals on weeks 10, 12, 13 and 14 of short-day treatment. Thus, short day exposure results in a simultaneous loss of response of the hypothalamo-hypophysial axis to castration and initiation of refractoriness.

Animals↗

Pinealectomy and lesions of the suprachiasmatic nucleus affect the castration response in hamsters exposed to short photoperiods.

Castration of male hamsters that have been exposed to a nonstimulatory photoperiod (e.g., LD 6:18) results in an attenuated increase in serum LH and FSH levels when compared to the increase observed following castration of hamsters exposed to a stimulatory photoperiod (e.g., LD 14:10). The short-day-induced inhibition of pituitary gonadotropin release, which is not dependent on the negative feedback effects of gonadal steroid hormones, is abolished if (1) the animals are transferred to LD 14:10; (2) the suprachiasmatic nuclei are lesioned at the time of castration; or (3) pinealectomy accompanies castration. These results indicate that both the pineal gland and the SCN mediate the steroid-independent inhibition of pituitary gonadotropin release that occurs during exposure to short days.

Animals↗

Age-related differences in the effect of castration upon hypothalamic LHRH content in male rats.

Male rats aged between 15 and 75 days were orchidectomized or only anesthetized. After various periods from 2 h to 42 days, 8 animals of both groups were sacrificed. Serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as well as the hypothalamic luteinizing hormone-releasing hormone (LHRH) content were determined by radioimmunoassay. At the times studied within 15 days of castration, no significant change in hypothalamic LHRH content was observed in rats orchidectomized at 21 days of age. However, when studied 3-6 weeks after castration, those animals showed a reduced hypothalamic LHRH content. No differences were observed between anesthetized and orchidectomized rats aged 15, 18 or 21 days and studied 1 week later. In contrast, castration of 75-day-old rats resulted in a significant reduction of the hypothalamic LHRH content after 2-15 days. A significant decrease was also observed 1 week after orchidectomy of rats aged 24-50 days. 1 day after orchidectomy, LH and FSH serum levels were markedly increased in 21- as well as 75-day-old rats. In the latter, serum LH concentrations did not change any further whereas in the former a plateau was only seen after 1 week. In rats orchidectomized at various ages ranging from 15 to 50 days, no consistent differences appeared in serum gonadotropin concentrations evaluated 7 days later. According to these data, variations in hypothalamic LHRH content after orchidectomy differ according to age and maturity. In 15- to 21-day-old rats, the age-related increase in hypothalamic LHRH content was not immediately affected by castration as it was in older animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Effects of castration and testosterone on the pituitary and adrenal responses of the newborn rat to ether inhalation.

In 8-day-old rat newborns, the pituitary response to 2 min of ether inhalation was noted to vary according to sex. Plasma ACTH levels were similarly increased in males and females at the end of ether exposure; however, during the following 30 min, ACTH levels were always higher in females than in males. In order to verify that the putative masculinization of some neuroendocrine pathways involved in the pituitary response to ether stress was the result of the transitory surge of testosterone at birth, fetuses at term were delivered by cesarean section and thereafter immediately castrated or sham-castrated under cold anesthesia (males), injected with testosterone heptylate (1 mg s.c.) or olive oil used as solvent (females) before being put in the care of a nurse. The rise in plasma testosterone levels during the 1st h after birth was prevented or stopped in males put at 2 degrees C. At the 8th postnatal day, the newborns were subjected to 2 min of ether inhalation; they were sacrificed either just, before or after the end (0 and 30 min) of the stress procedure. Plasma immunoreactive ACTH level and adrenal corticosterone content were measured. The pituitary response, shown by the ACTH increase, in castrated or sham-castrated males and testosterone-injected females was similar to that of intact males but very different from that observed in olive-oil-injected or intact females. The rise in adrenal corticosterone content 30 min after ether inhalation was greater in intact and olive-oil-injected females than in testosterone-injected ones or in males; adrenal response was well correlated with the maintenance of ACTH release in the former and the decrease following transitory surge in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

Effect of denervation or castration on ultrastructural and histochemical properties of feline bulbocavernosus muscle.

The histochemical and ultrastructural changes in the mature feline bulbocavernosus muscle (BCM) induced after 10 days of denervation or castration were compared. Control BCM, denervated BCM, and BCM from castrated cats reacted similarly for myosin ATPase (predominantly dark staining) and for succinic dehydrogenase (predominantly high). Staining for phosphorylase was decreased in the denervated BCM and BCM from castrated cats. Intrafiber lipid content was reduced after denervation or castration. The appearance of lysosome-like structures in BCM from both treatment groups was the most obvious ultrastructural alteration. Other ultrastructural changes were focal and infrequent.

Animals↗

Effect of castration on the experimental renal hypertension of the rat. Blood pressure, nephrosclerosis, long-chain fatty acids, and N-acetylation of PAH in the kidney.

Rats were rendered hypertensive by clamping one renal artery. Both kidneys remained in situ ('two-kidney one-clip Goldblatt hypertension'). Half of the animals were simultaneously castrated. 18-24 weeks after the operation both castrated females and males had a lower level of hypertension than the uncastrated controls. The kidneys of castrates contained less connective tissue (measured as the content of hydroxyproline) and long-chain (C-18) fatty acids and had a higher specific activity of the enzyme N-acetylating p-aminohippurate (N-acetyltransferase) than those of uncastrated rats. Thus, castration seems to alleviate some renal effects of the Goldblatt hypertension. In all animals the clamped kidney contained more hydroxyproline and C-18 fatty acids and had a lower N-acetyltransferase activity than the contralateral untouched organ. These results are in accordance with the theory that renal fatty acid concentration interferes directly with the N-acetyltransferase activity of the kidney. The enhanced hydroxyproline content of the kidneys (nephrosclerosis) inhibits N-acetylation most probably indirectly by raising the tissue concentration of C-18 fatty acids.

Acetyltransferases↗

Reversal by testosterone of atrophy of accessory genital glands of castrated male sheep. A histologic and morphometric study.

The histologic features of male accessory genital glands of entire sheep (group I), castrated sheep (group II), castrated sheep treated with 40 daily intramuscular injections of 50 milligrams testosterone propionate (group III), and castrated sheep treated with 600 milligrams testosterone propionate 72 hours before death (group IV) were compared. Sheep were castrated at 3 months old and all sheep were killed when 15 months old. Volume fractions of glandular tissue, intralobular fibromuscular tissue and perilobular fibromuscular tissue of the seminal vesicles and Cowper's glands fluctuated significantly (P less than 0.05) during postcastration atrophy and after repeated testosterone treatment. Atrophy in sheep in group II was least in the prostate but greatest in Cowper's glands, seminal vesicles and ampullae of vasa deferentia. Seminal vesicle plexi, whose cytons had a statistically significant (P less than 0.05) degree of shrinkage, also were atrophied. After treatment with testosterone the postcastration atrophy of plexal neurons was almost reversed in sheep in group III. There also was hypertrophy of epithelial cells but the testosterone treatment failed to reduce to normal the fibromuscular volume fraction of the accessory genital glands. Testosterone propionate treatment of sheep in group IV failed to elicit appreciable morphologic changes. These results are compared with our previous findings on the content and uptake of zinc by the accessory genital glands. It is suggested that accumulation of zinc in the accessory genital glands of sheep is not necessarily closely linked to normal histologic appearance.

Animals↗

Ultrastructural localization of prolactin in the rat anterior pituitary glands by preembedding peroxidase-labeled antibody method: observations in normal, castrated, or estrogen-stimulated specimen.

Ultrastructural localization of prolactin (PRL) was studied immunocytochemically (preembedding peroxidase-labeled antibody method) in a variety of pituitaries, including those from 1) normal, 2) castrated, and 3) castrated and estrogen-stimulated rats. In the normal rat, PRL was observed in cisternae of the rough endoplasmic reticulum (RER), perinuclear spaces, Golgi saccules, and secretory granules. In the castrated rats, PRL cells were rather atrophic and were filled with many small PRL-positive secretory granules. RER and Golgi saccules were rather inconspicuous and were almost devoid of PRL localization. The serum PRL level was markedly lowered. With estrogen stimulation after castration, the serum PRL level was markedly elevated and PRL cells showed a pronounced increase of PRL filled cisternae in the RER. From these observations, the role of secretory granules, Golgi apparatus, and RER in hormonal secretion was defined, and it was postulated that some peptide hormones would be secreted along two alternative pathways, i.e., either 1) a long (regulated) pathway or 2) a short (accelerated) pathway, in accordance with their secretory activities, which could be altered by various stimulations such as the use of estrogen.

Animals↗

Increase in pituitary levels of luteinizing hormone and follicle-stimulating hormone after pinealectomy in both intact and castrated male rats.

Twenty-eight-day-old male Wistar rats were pinealectomized and/or castrated. Animals were killed 26 days later and anterior pituitaries were dissected out, weighed, and their content of LH and FSH measured by RIA. Pinealectomized rats showed higher body weights than sham-operated animals, which suggests an inhibitory influence of the pineal on growth. The weights of pituitaries were increased by both pinealectomy and castration. However, in pinealectomized rats, but not in castrated, the elevated pituitary weights seemed to be due to the high body weights of those animals. The pituitary content and concentration of LH and the content of FSH were increased by pinealectomy in both intact and castrated rats. This finding may suggest that the pineal gland exerts an inhibitory action on the hypothalamic-pituitary axis that seems to be independent of the testicular function.

Animals↗

Influence of estrogen-progesterone combinations on gonadotropin secretion in castrate female rats(1).

In order to study the effect of progesterone in modulating the secretion of gonadotropins, various doses of progesterone were administered to castrated immature and mature female rats. Progesterone did not prevent the postcastration rise of FSH and LH in these animals. Various amounts of progesterone were then administered to castrated rats that were treated with a constant low dose of estradiol. In animals given doses of estradiol that were able to decrease serum FSH and LH below castrate levels, but not to prevent the post-castration rise, the effect of progesterone was dose-dependent. A very low dose of progesterone lowered serum gonadotropins, an intermediate dose brought about an increase in secretion, and high doses were suppressive. The modifying action of progesterone appears to be dependent upon the level of estrogen, the dose of progesterone, and the time of administration.

Age Factors↗

The effects of castration and treatment with testosterone on the biliary excretion of (3H)aldosterone in rats.

The rate of excretion of aldosterone radiometabolites into the bile duct cannulation, and the intravenous injection of (3H)aldosterone, was demonstrated to be markedly increased in male rats following castration. In 1 h, 72% of the injected 3H-radioactivity was excreted in the bile of castrated male rats compared with 26% in the intact male control rats. Castration of the males led to the increased biliary excretion of aldosterone metabolites and the elimination of the sex-dependence of this process in rats. The ovariectomy of female rats did not substantially increase the rate of excretion of aldosterone metabolites via the bile. Castrated male rats treated with testosterone excreted aldosterone metabolites into the bile at a slower rate. A similar treatment of ovariectomized female rats with testosterone also significantly slowed the rate of biliary excretion of the aldosterone metabolites. These findings suggest that the presence of androgens plays an important role in regulating the routes of hepatic metabolism of aldosterone and the rates of clearance of aldosterone and its metabolites from the plasma into the bile of rats.

Aldosterone↗

The effect of different doses of oestradiol-17 beta on collagen synthesis in the femur of castrated female rats.

The effect of different doses of oestradiol-17beta on collagen metabolism in the femur of castrated young mature female rats was studied. The animals received daily injections of the hormone for 21 days and 25 muCi [14C] proline was injected intraperitoneally 24 h before the rats were sacrificed. The rats receiving 1 mug oestradiol per day had a significantly higher specific activity of hydroxyproline in bone compared to the normal and the castrated control rats. At the same time the bone weights and collagen content per femur was less in the rats receiving oestradiol 1 and 2 mug/day than in the control animals. The higher specific activity of bone hydroxyproline in the rats receiving oestradiol-17beta 1 mug/day did not, however, indicate a higher bone collagen accretion rate. As all rats received the same amount of [14C] proline, and the body weights differed considerably at sacrifice, tha naimals probably had different tissue fluid concentrations of [14C] proline. This possibility was supported by the observation that serum concentrations of radioactivity were inversely correlated to body weights. "Correcting" for differences in body weights, the castrated control rats turned out to be the group with the highest specific activity. On doses of 10 and 20 mug oestradiol-17beta per day, the specific activity of hydroxyproline in bone was lower than in the control rats while bone weights and collagen content of the femur were not different from the corresponding values of the castrated controls. This finding suggests a "slow down" of collagen metabolism - both with regard to the accretion and the resorption.

Animals↗

Peripheral and central androgenic stimulation of sexual behaviour of castrated male rats.

The effects of androgens on the maintenance and restoration of sexual behaviour (mounts, intromissions and ejaculations) of castrated male rats were studied. In the maintenance study the rats were treated during 5 weeks, starting one day following castration. Testosterone propionate maintained sexual behaviour at an almost normal level. The androgenoestrogen intermediate 19-hydroxytestosterone propionate was unable to prevent the decline in the number of ejaculations over the weeks although this hormone maintained the post-ejaculatory refractory period in those rats that ejaculated and also maintained normal sexual latencies. In the restoration study administration of testosterone propionate during 7 weeks to long-term castrated rats restored sexual behaviour to normal. 19-Hydroxytestosterone propionate treated rats displayed mounts but no other signs of sexual behaviour. The 5alpha-reduced androgen dihydrotestosterone propionate did not restore sexual behaviour. Testosterone propionate and dihydrotestosterone propionate stimulated peripheral target organs; 19-hydroxytestosterone propionate was ineffective in this respect. It has been suggested that testosterone might stimulate sexual behaviour in rats in two ways, i.e., via its aromatization to oestradiol in the brain, andy by stimulating growth of peripheral tissues via its 5alpha-reduction to dihydrotestosterone. In support for this view we have found that the combination of 19-hydroxytestosterone propionate and dihydrotestosterone propionate was effective in restoring the full pattern of sexual behaviour in castrated male rats.

Animals↗

The time course change after castration in short-loop negative feedback control of LH by HCG in women.

The time course of change in the suppressive effect of human chorionic gonadotrophin (HCG) on luteinizing hormone (LH) and/or LH-beta following castration was studied by a specific LH-beta radioimmunoassay. At 14-50 days after castration 8 women were given 10 000 IU of HCG in a single intramuscular injection (group 1), 5 women were given 2000 IU of HCG in the same way (group 2), and 5 were injected with saline as controls (group 5). In addition, 5 women 6-15 months (group 3) and 7 women 3-8 years (group 4) after castration were given 10 000 IU of HCG. The serum concentrations of HCG in groups 1, 2, 3 and 4 reached peak levels of 209.4, 44.1, 210.6 and 238.6 uU/ml, respectively, 4 h after the HCG injection. The serum LH concentration in group 1 was reduced significantly (P less than 0.01) by HCG administration, but the reductions in the LH levels in groups 2, 3 and 4 after HCG injection were not significantly different from that of the controls. These findings suggest that the threshold of the short-loop negative feedback control of LH in women changes with time after castration.

Adult↗

The TSH response to TRH is exaggerated in primary testicular failure and normal in the male castrate.

Basal TSH levels and the TSH response to TRH have been evaluated in 26 males aged 20-48 years with primary testicular failure, and 6 males aged 58-69 years who had been orchidectomised for prostatic carcinoma. The patients with testicular failure were sequentially challenged at 30 min intervals with iv LRH (100 microgram), TRH (200 microgram) and the dopaminergic antagonist, metoclopramide (10 mg). The castrates received a bolus of LRH and TRH given together. The responses in the 2 patient groups were compared to a group of 28 healthy male controls aged 20-40 years, who received the sequential protocol and 8 elderly controls aged 65-79 years, who were given the LRH, TRH bolus. Mean +/- SD basal TSH levels were 3.0 +/- 1.2 muU/ml in primary testicular failure and significantly greater than both control and castrate groups. The peak TSH response to TRH was 18.4 +/- 7.4 muU/ml in testicular failure and significantly greater than in the young controls, where it was 11.5 +/- 5.0 muU/ml. The peak levels in the castrates and in the elderly controls were similar to the young male controls. Total T4 and T3, as well as FTI, primary testicular failure had a reduction in their T3 resin uptake. The normal TSH profile in the castrates indicates that a testicular factor produces the exaggerated responses in primary testicular failure.

Adult↗

Relationships between fat and plasma androstenone and plasma testosterone in fatty and lean young boars following castration.

The effect of weight of fatty tissue on fat and plasma androstenone and on plasma testosterone relationships was studied in the young boar following castration. For this purpose, 9 boars were castrated at 175 days of age, plasma steroid levels were determined daily up to 10 days after orchidectomy and fat androstenone concentration was measured 1, 3, 6, 10 and 15 days after castration. The results show that the apparent half-life of stored androstenone is very variable between boars (range: 4 to 14 days) and do not depend on the weight of fatty tissue. The rate of elimination of plasma androstenone is also very variable between boars. The rate of disappearance of fat androstenone following castration does not depend on the rate of androstenone release from fatty tissue to peripheral plasma but is more likely dependent on the intensity of plasma androstenone catabolism and elimination. Therefore, fat androstenone concentration in the intact boar is almost only depending on the equilibrium between the respective rates of testicular production and elimination.

Adipose Tissue↗