摘要:

Twelve days after hypophysectomy depleted atrial natriuretic polypeptide (ANP) concentrations were measured in the plasma and in 8 of 18 microdissected brain nuclei of rats. Reduced ANP levels were found in brain structures (subfornical organ, organum vasculosum laminae terminalis, preoptic and hypothalamic periventricular nuclei, paraventricular nucleus, lateral hypothalamic area), which are directly involved in the central regulations of salt and fluid homeostasis, as well as in the medial amygdaloid nucleus and the locus ceruleus. ANP concentrations in the median eminence, medial preoptic and arcuate nuclei did not alter by hypophysectomy. Elevated ANP concentrations were measured only in the supraoptic nucleus of hypophysectomized rats.

ISSN:0028-3835    

DOI:10.1159/000126229

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Previous studies have shown that pyridostigmine (PD) is capable of increasing the growth hormone (GH) response to GH-releasing hormone (GHRH) in young healthy subjects. In order to investigate the influence of age and sex on the PD potentiation of GHRH-induced GH release, we have studied the GH response to GHRH (50 µg i.v.) 1 h after oral administration of placebo or PD (60 mg) in 8 young healthy men (aged 19-28 years) and 8 age-matched young women (aged 18-25 years) during the follicular phase of the menstrual cycle, as well as in 8 postmenopausal women (aged 57-62 years) and 8 age-matched elderly men (aged 56-64 years). In the same subjects the effect of PD alone (60 mg p.o.) was also studied. Furthermore, in 6 postmenopausal women and 6 elderly men, the effect of a 30-mg PD oral dose on GH secretion and GH response to GHRH was evaluated with a similar protocol. The GH responses (mean ± SE) to GHRH + placebo were similar in young men (peak 20.1 ± 2 ng/ml, AUC 1,250 ± 113 ng/ml/min) and women (peak 29.3 ± 2.3 ng/ml, AUC 1,769 ± 305 ng/ml/min). PD 60 mg was capable of significantly increasing the GH response to GHRH in young men (peak 43.5 ± 5.1 ng/ml, AUC 3,734 ± 472 ng/ml/min, p < 0.005) but not in women (peak 39 ± 2.3 ng/ml, AUC 2,479 ± 205 ng/ml/min). The GH responses to GHRH + placebo were also similar in postmenopausal women (peak 6.2 ± 0.7 ng/ml, AUC 540 ± 80 ng/ml/min) and age-matched men (peak 11.3 ± 0.6 ng/ml, AUC 763 ± 73 ng/ml/min) although these responses were significantly decreased when compared to those observed in young individuals. PD 60 mg administration induced a significant increase in GH response to GHRH both in postmenopausal women (peak 27 ± 3.6 ng/ml, AUC 2,224 ± 251 ng/ml/min, p < 0.001) and elderly men (peak 49.7 ± 2.4 ng/ml, AUC 4,557 ± 263 ng/ml/min, p < 0.001). The GH increment, however, was greater in elderly men than in postmenopausal women (p < 0.005). In young men, elderly men and postmenopausal women, PD 60 mg potentiated the action of GHRH rather than merely being additive. A similar effect was observed when a 30-mg PD dose was preadministered in elderly men and women. Our data clearly demonstrate a marked influence of age and sex on the PD potentiation of the GHRH-stimulated GH secretion. PD significantly potentiated GH responses to GHRH in young men, elderly men and postmenopausal women but n

ISSN:0028-3835    

DOI:10.1159/000126230

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We recently reported that pituitary gonadotropes, major targets of circulating inhibins and activins, are also capable of synthesizing the inhibin (I) α- and inhibin/activin (I/A) βB-subunits. In the present study, we examined the sub-cellular distribution of these subunits, with special attention given to determinating the extent to which they might be colocalized with the gonadotropins in secretory granules. Pituitaries from adult male rats were cryofixed, molecular distillation-dried, and resin-embedded. Immunogold staining methods were used to examine concurrently the distributions of an I/A subunit and FSH or LH. I/A subunits were detected only in cells that also labeled positively for a gonadotropin, and, in contrast to the gonadotropins, were sequestered almost exclusively within secretory granules. The Iα-subunit colocalized with FSH in 31%, and with LH in 36%, of all positively stained granules. The I/AβB-subunit was found with FSH or LH in about 25% of the granules. Approximately 52-69% of the granules contained FSH or LH alone; 7–18% were positive only for an I/A subunit, and this varied as a function of the particular gonadotropin with which costaining was carried out. Dual staining for the Iα-and the I/AβB-subunits indicated that at least 35% of all immunolabeled granules showed positive signals for both subunits. Coupled with methodological considerations to indicate that these estimates of the extent of colocalization are likely to be conservative, these data suggest that inhibin and activin are characteristically copackaged, and presumably coreleased, with the gonado

ISSN:0028-3835    

DOI:10.1159/000126231

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The specific binding of 125I-human prolactin (hPRL) was studied in different areas of the human brain. Particularly high binding affinity of the hormone was found in the choroid plexus and this tissue was therefore selected for further studies. The hippocampus, the hypothalamus and the pituitary were among other regions containing prolactin-binding sites. In the choroid plexus the amount of PRL receptors was significantly higher in females than in males and was also found in both sexes to decrease with age. The binding affinity of 125I-hPRL to choroid plexus was 3.0 × 109M-↑and the binding capacity was 10.3 pmol per mg protein. Following solubilization with Triton X-100 the PRL receptor fraction retained its hormone-binding properties and upon molecular sieve chromatography it behaved as a protein with a molecular mass of approximately 250,000. Cross-linking of I25I-hPRL to receptors from choroid plexus and subsequent sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis indicated a major hormone-binding unit of Mr 44,000. This value is about 7,000 smaller than that reported earlier by us for the growth hormone receptors from the same tissue, following cross-linking to 125I-human growth hormone (hGH). By affinity column chromatography a complete separation of the hPRL and hGH binding units was achieved. It was thus shown that in choroid plexus the binding sites for GH and PRL occur as discrete entiti

ISSN:0028-3835    

DOI:10.1159/000126232

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

There are data indicating that stress-induced prolactin (PRL) release is blunted in the lactating rat like the release of other stress-associated hormones. In this experiment, the PRL release evoked by administration of estrogen, which is another principal stimulus for PRL release, was examined in ovariectomized lactating rats 8-15 days after delivery. Estradiol benzoate (EB, 20 µg) injections into ovariectomized nonlactating rats induced a PRL surge starting between 13:00 and 15:00 h with a peak at 17:00 h 2 days after the treatment, whereas the EB-induced PRL surge was absent in ovariectomized lactating rats separated from their pups at 09:00 h on the day or in mothers without separation from their pups. Injection of either thyrotropin-releasing hormone (TRH; 10 µg/kg) or pimozide (0.5 mg/kg) elevated serum PRL concentrations similarly in lactating and nonlactating rats when examined just before the beginning of the expected estrogen-induced PRL surge. Thus, the main cause for the reduced PRL response to estrogen in lactating rats seems not to be in the pituitary gland but in the brain. Progesterone, which is know to induce a PRL surge in ovariectomized estrogen-primed rats by acting on the mediobasal hypothalamus, also failed to evoke a PRL surge in lactating rats. Recovery from the inhibitory influence of suckling on PRL response to EB followed a time course similar to that observed in response to immobilization stress or to morphine injection; estrogen-induced PRL surge started to recover at 6 days and was almost fully recovered 8 days after weaning. These facts indicate that suckling stimuli may cause functional alterations in the neural systems responsible for PRL release, resulting in refractoriness of the PRL response to ovarian steroid

ISSN:0028-3835    

DOI:10.1159/000126233

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Somatostatin receptors on lactotroph cells of the anterior pituitary are positively regulated by estradiol. In the present work, we investigated whether estradiol regulation of somatostatin receptors also occurred in the female rat brain. 125I-Tyr0-DTrp8-somatostatin (125I-SRIF: 780 Ci/mM) was used as a ligand. Female adult rats were ovariectomized and treated or not with estradiol benzoate (20 µg/day for 1 or 8 days). In female brains, 125I-SRIF binding, as assessed by film radioautography, was high in the basolateral amygdala, CA1 field and dentate gyms of the hippocampus and locus coeruleus, moderate in the median habenula and deep layers all through the cortex. Castration or estradiol treatment did not modify 125I-SRIF binding in these regions. By light-microscopic radioautography, a subpopulation of 125I-SRIF-labeled cells was localized in the ventrolateral portion of the arcuate nucleus. Ovariectomy alone did not significantly affect the number and binding density of 125I-SRIF-labeled cells in the arcuate nucleus. However, estradiol treatment in ovariectomized animals significantly increased both parameters. Along the estrus cycle, the number of 125I-SRIF-labeled cells was not significantly modified but 125I-SRIF binding density was significantly higher in proestrus as compared to diestrus I, diestrus II and estrus. These results demonstrate that brain 125I-SRIF binding sites are positively regulated by estradiol only in the arcuate nucleus of the hypothalamus

ISSN:0028-3835    

DOI:10.1159/000126234

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Endogenous opioid peptides (EOPs) stimulate prolactin (PRL) release in various physiological conditions in the rat. Moreover, EOPs are essential in initiating and maintaining the nocturnal PRL surges that occur over the first half of gestation in the rat. The purpose of this study was to investigate the potential role of the opioid β-endorphin (β-End) in mediating the nocturnal PRL surges. Day 8 pregnant rats received an infusion of 2.5, 10, 25 or 100 ng/µl/min β-End intracerebroventricularly (i.c.v.) for 15 min at 12.00 h, an intersurge period. PRL increased in a dose-dependent manner and from this, the largest dose was used in subsequent experiments to ensure maximal opioid receptor stimulation. The next experiment defined the temporal sensitivity of the neuroendocrine system regulating PRL surges to exogenous β-End. Day 8 pregnant rats showed dramatic PRL responses to β-End when given at midnight (presurge) or 12.00 h (intersurge), but greatly attenuated responses at 02.00 h (early surge) and 04.00 h (late surge). Animals treated at 06.00 h (postsurge) showed recovered responsiveness to β-End. To determine what may account for the significantly lower PRL increases to β-End during the surge, day 8 pregnant rats received 100 ng/µl/min β-End i.c.v. for 15 min at 10.00 h, and then again at 12.00 h. All animals showed PRL increases greater than 1,140 ng/ml at 10.00 h, but the subsequent response to β-End at 12.00 h was reduced by 70%. In another experiment, β-End was infused at midnight and the animals were monitored for a subsequent endogenous nocturnal PRL surge. Although all animals showed a rapid increase in PRL following β-End treatment, 5 of 8 animals did not have a nocturnal PRL surge. This suggests that the initial β-End may downregulate its receptors, and therefore account for the much lower PRL response to β-End during the surge. To determine whether an insufficient amount of pituitary PRL may account for the small response to β-End during the surge, hemipituitary PRL concentration was measured. Pituitary PRL concentration was found to be lower at 04.00 h, when the incremental increase in plasma PRL to β-End was smallest, compared to the concentration at midnight, when the response was highest. However, at 02.00 h, pituitary PRL levels were similar to those at midnight, yet the PRL response to β-End differed greatly at these 2 times. Based on these results, lower pituitary PRL concentration during the nocturnal surge may only partially account for the attenuated PRL response to β-End. Downregulation of β-end receptors or less dopamine available for inhibition by β-End in the tuberoinfundibular dopamine neurons also are

ISSN:0028-3835    

DOI:10.1159/000126235

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Pituitary oxytocin (OT) secretion is inversely related to saline consumption in several experimental models of sodium appetite in rats. Because systemic OT administration does not inhibit sodium appetite, release of OT as a neurotransmitter within the brain, coincident with its secretion from the pituitary, may be related to inhibition of sodium ingestion. The present studies evaluated this possibility by increasing brain OT concentrations both exogenously and endogenously in rats with hypovolemia produced by subcutaneous administration of polyethylene glycol (PEG) solution. Intracerebroventricular (i.c.v) administration of OT completely abolished intake of 0.5 M NaCl in PEG-treated hypovolemic rats, but did not significantly affect PEG-stimulated water intakes. Endogenous OT secretion was stimulated by systemic treatment with naloxone, which has been shown to increase peripheral and central OT levels. In both one-bottle (0.5 M NaCl) and two-bottle (water and 0.5 M NaCl) drinking tests, intraperitoneal naloxone completely abolished sodium appetite in association with markedly increased pituitary secretion of OT. This inhibition of sodium appetite could be prevented by i.c.v. pretreatment with a specific OT-receptor antagonist, although the antagonist by itself did not affect PEG-stimulated sodium intake. These findings therefore support previous reports which have found that sodium appetite in rats is inhibited by treatments that elicit pituitary release of OT, and provide more direct evidence that brain OT is causally involved in the inhibition of sodium appetite stimulated by such treatments in rats.

ISSN:0028-3835    

DOI:10.1159/000126236

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

To investigate possible mechanisms whereby the augmentation of hypothalamic proopiomelanocortin (POMC) messenger ribonucleic acid (mRNA) levels occurs with pubertal development, we employed the techniques of testosterone administration and in situ hybridization histochemistry in sexually immature male rats. Six animals from each of the following groups were studied: (1) untreated controls (CTRL); (2) empty capsule (SHAM); (3) testosterone capsule (TEST), and (4) untreated adults (ADLT). Capsules were implanted at 21 days of age. Groups 1-3 were sacrificed at 35 days of life; group 4 at 55 days. Ventral prostate and seminal vesicle weights were obtained to assess the biologic effect of testosterone. Hybridizations were performed on coronal brain slices through the region of the arcuate nucleus using a 35S-labeled oligonucleotide probe complementary to a 30-base sequence within POMC mRNA. Anatomically matched tissue sections (11 per animal, from the retrochiasmatic region rostrally to the premammillary nucleus caudally) were exposed to x-ray film, followed by densitometric analysis. The mean serum testosterone concentration of the TEST group was significantly greater than that of the ADLT animals; values for the CTRL and SHAM rats were undetectable. The accessory sex organ weights of the ADLT animals were greater than those of the TEST rats; both values were greater than those of the CTRL and SHAM groups which were indistinguishable. Increased levels of hypothalamic POMC mRNA were observed in the male rat after pubertal development. However, no effect of exogenous androgen administration was demonstrable on hypothalamic POMC gene transcript levels in sexually immature rats despite an observed biologic effect of increased size of the accessory sex organs. These findings suggest that gonadal steroid hormones alone are insufficient, at least in the prepubertal state, to stimulate the expression of the hypothalamic POMC gene. Additional factors, such as those responsible for the initiation of puberty and maturational processes of puberty, may be important in the regulation of POMC gene expression.

ISSN:0028-3835    

DOI:10.1159/000126237

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The obese Zucker rat (fa/fa) is an animal model for genetic obesity characterized by hyperphagia, hyperinsulinemia, and severe insulin resistance in peripheral tissues. Adrenal steroids seem to play an important role in the onset of fatty syndrome in these animals. There is strong evidence of abnormal regulation of the hypothalamic-pituitary-adrenal axis in obese Zucker rats. Considering the physiological function of arginine vasopressin (AVP) as an adrenocorticotropic hormone secretagogue, the present study was carried out to investigate the role of glucocorticoids in the control of hypothalamic AVP systems in lean and obese Zucker rats. In the first experiment, mifepristone (RU 38486), a glucocorticoid receptor antagonist, was administered for 4 days (10 mg/kg orally twice daily), and the expression of AVP mRNA in hypothalamic paraventricular and supraoptic nuclei was measured using in situ hybridization, and the concentrations of AVP in the pituitary gland and in the median eminence were quantified. Plasma corticosterone levels were also analyzed. Mifepristone treatment resulted in a threefold increase in plasma corticosterone levels in lean Zucker rats, but it did not change corticosterone secretion in obese animals. Mifepristone treatment decreased AVP mRNA levels in lean animals in the supraoptic nuclei, while in obese animals the AVP mRNA content was increased in the paraventricular nuclei. Mifepristone treatment significantly increased the concentration of AVP in the median eminence in lean rats and decreased it in obese animals. Mifepristone treatment did not change concentrations of AVP in the pituitary gland. In the second experiment, mifepristone was given for 4 days (10 mg/kg orally twice daily), and its effects on 24-hour food intake and plasma AVP concentrations were measured. Mifepristone treatment significantly increased the plasma AVP concentrations in lean animals, while in obese rats the plasma AVP levels remained unchanged. Basal plasma AVP levels were significantly higher in obese as compared with lean rats. The food intake was not changed by mifepristone. Our results suggest that blockade of glucocorticoid receptors, not resulting in complete adrenal insufficiency like adrenalectomy, differentially modulates hypothalamic AVP systems in lean and obese Zucker rats. This may be associated with the inability of mifepristone to activate the hypothalamic-pituitary-adrenal axis in obese animals which may be due to aberrant glucocorticoid receptor regulation in established genetic obesity.

ISSN:0028-3835    

DOI:10.1159/000126238

出版商:S. Karger AG    

年代:1992

数据来源: Karger