摘要:

The effect of various doses of the 5-HT agonist m-chlorophenylpiperazine (MCPP) on neuroendocrine function (prolactin and corticosterone responses) were compared in three different rat strains: Wistar, Sprague-Dawley (SD), and Fawn-Hooded (FH) rats. Administration of various doses of MCPP produced increases in plasma concentrations of prolactin and corticosterone in all three rat strains. The prolactin responses of FH rats to MCPP were significantly smaller than that of either Wistar or SD rats, while corticosterone responses were equivalent across all three strains. On the other hand, baseline concentrations of corticosterone, but not of prolactin, were significantly higher in FH animals relative to both Wistar and SD animals. There was no significant difference in either baseline hypothalamic concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, or dopamine or brain concentrations of MCPP among these three rat strains. These findings support some other data indicating that FH rats, a strain with a peripheral platelet serotonin storage pool disorder, also possess alterations in some neuroendocrine functions which are modulated by serotonin.

ISSN:0028-3835    

DOI:10.1159/000125041

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

We studied the effects of selected leukotrienes and hydroxyeicosatetraenoic acids (HETEs) on prolactin release from primary cultures of female rat anterior pituitary cells. Leukotrienes B4, C4, and D4 had no effect on basal prolactin release; however, they did enhance prolactin release that was stimulated by 1 or 5 nM thyrotropin-releasing hormone (TRH). Leukotriene C4 also enhanced prolactin release that was induced by phorbol myristate acetate (a protein kinase C activator) by maitotoxin (a calcium uptake stimulator), and by angiotensin II. 5-HETE, 12-HETE, and 15-HETE stimulated basal prolactin release at high concentrations (1 µM and greater), and 5-HETE and 12-HETE enhanced TRH-and angiotensin II-induced prolactin release at lower (nanomolar) concentrations as well. In order to determine the role of endogenous arachidonate metabolites in prolactin release, pituitary cell cultures were exposed to selected inhibitors of the 5-lipoxygenase enzyme, which metabolizes arachidonate to leukotrienes and 5-HETE, and to those of the epoxygenase enzyme, which metabolizes arachidonate to epoxyeicosatrienoic acids. These inhibitors decreased basal and secretagogue-induced prolactin release. In additional experiments, it was determined that TRH enhances the liberation from pituitary cells of arachidonate metabolites with high-performance liquid chromatography elution profiles similar to those of leukotriene C4 and ω-OH-leukotriene B4 (a metabolite of leukotriene B4) and the HETEs. Therefore, the production of leukotrienes, HETEs, and epoxyeicosatrienoic acids may be necessary for the normal release of prolacti

ISSN:0028-3835    

DOI:10.1159/000125042

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Plasma adrenocorticotropic hormone (ACTH) and corticosterone were detectable in fetal plasma on day 16 of pregnancy. Thereafter, the levels of both hormones increased steadily in a parallel manner and reached a peak on day 19 of pregnancy. Administration of an antiserum anti-rat corticotropin-releasing factor (CRF) to pregnant rats was followed by a significant decrease in fetal plasma corticosterone as early as day 17. Plasma ACTH measured under the same experimental conditions on day 19 of gestation was also significantly decreased. Similar results have been obtained with fetal plasma collected from adrenalectomized pregnant rats, indicating that the plasma corticosterone decrease in fetuses after immunoneutralization of CRF reflects changes in fetal adrenal secretion and not a diminution of corticosterone transfer from the maternal to the fetal circulation. These results show that endogenous CRF begins to play a physiological role in the regulation of ACTH and corticosterone secretion as early as in 17-day-old fetuses. This effect may occur before the connections between the neurosecretory CRF axons and the hypophysial portal capillaries have been established. Therefore, endogenous CRF may enter the hypophysial portal circulation after intercellular diffusion in hypothalamic tissue.

ISSN:0028-3835    

DOI:10.1159/000125043

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The pituitary glands were removed from 63 human fetuses from 5 weeks of gestation to term and studied by electron microscopy and ultrastructural immunocytochemistry to document the development of cell differentiation and hormone production in the adenohypophysis. At 5 weeks of gestation, Rathke’s cleft was lined by columnar epithelium with abundant cytoplasmic glycogen and occasional secretory granules. By 6 weeks of gestation, cells resembling corticotrophs were identified; in 8-week-old fetuses, type I microfilaments were found in those cells. Well-differentiated somatotrophs were seen in adenohypophyses of 8- to 9-week-old fetuses. Although secretory granules were numerous, the Golgi complex was inconspicuous in early fetal glands. After 10 weeks of gestation, there was a change with morphologic evidence of active hormone secretion; large Golgi regions and sparsely granulated cells were found. Some somatotrophs at this stage contained aggregates of type II microfilaments which resembled the fibrous bodies of sparsely granulated somatotroph adenomas. Densely granulated mammosomatotrophs containing growth hormone and prolactin were identified at 12 weeks of gestation. Cells with characteristics of the glycoprotein hormone cell line were seen in pituitaries at 12 weeks of gestation; thyrotrophs and gonadotrophs were identified after 15 weeks. Typical lactotrophs were not recognized before 23 weeks, but were numerous in pituitaries of fetuses older than 35 weeks. This study documents for the first time the existence of a bihormonal mammosomatotroph in the human fetal pituitary and confirms that somatotrophs and lactotrophs, the two acidophil cell types, are embryologically related. Sparsely granulated somatotrophs appear after densely granulated somatotrophs at a time when fetal serum growth hormone reaches acromegalic levels, and it may be that the two cell types reflect differences in the hormonal milieu. The ultrastructural features of developing adenohypophysial cells resemble those of adenomas found in adult pituitaries, and fetal cytodifferentiation may help to clarify the significance of morphologic variants of adenoma

ISSN:0028-3835    

DOI:10.1159/000125044

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The gonadotropin-releasing hormone (GnRH) waveform arrives at the pituitary gonadotropes via the pituitary portal blood and provides the immediate suprapituitary stimulus to luteinizing hormone (LH) secretion. Despite their importance, nature and influence of the physiological GnRH waveform in vivo have been difficult to study. Recent pharmacological and in vitro studies have suggested the potential importance of the wave contour as a specific and independent factor in the pharmacodynamic effects of GnRH on pituitary gonadotrope LH secretion in vivo, and it has been hypothesized that the steepness of the rising edge of the GnRH wave contour is a specific determinant of pituitary LH secretion. In order to investigate the pharmacodynamic influence of GnRH pulse wave contour on pituitary LH secretion in vivo, variations in plasma LH responses to alterations in GnRH wave contour were measured in chronic ovariectomized, hypothalamopituitary-disconnected sheep undergoing physiological pulsatile GnRH maintenance regimen at a fixed dose (250 ng/pulse) and frequency (interpulse interval 120 min). Variable wave contours were then generated by administration of the same total GnRH pulse dose over various lengths of time from near-instantaneous bolus to increasing lengths of constant-rate infusion time up to 18 min. This model allowed specific examination of pulse wave contour in the absence of concurrent changes in endogenous GnRH or sex steroid secretion and holding constant GnRH pulse dose, frequency, and route of administration. Prolongation of the pulse infusion interval from rapid bolus to 6, 12, and 18 min with a consequent progressive flattening of the GnRH waveform in the bloodstream produced distinctive time course changes (p < 0.0001) with a progressive decrease (p < 0.0001) and delay (p < 0.0001) in peak as well as reduced net (p < 0.0001) LH secretion. These single-dose pharmacodynamic results provide direct support for the hypothesis that the wave contour of a GnRH pulse is a significant determinant of pituitary LH secretion in vivo in sheep. Together with the observed heterogeneity of GnRH patterns in pituitary portal plasma, this suggests the existence of an additional novel mode of hypothalamic regulation of pituitary LH secretion, that of the modulation of the GnRH waveform in the pituitary portal blood.

ISSN:0028-3835    

DOI:10.1159/000125045

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The antinociceptive effect of morphine (5 mg/kg body weight i.p.) in rats subjected to various experimental manipulations of the pituitary-adrenocortical system was studied. The absence of adrenal steroids increased the sensitivity to morphine. The following findings suggest that glucocorticosteroids have a long-lasting influence on opioid-induced antinociception, even when the steroids have been removed by adrenalectomy. First, when rats were adrenalectomized in the morning under basal conditions of pituitary-adrenocortical activity (plasma corticosterone level < 1 µg%), the subsequent hypersensitivity to morphine was more pronounced than when rats were adrenalectomized in the evening (plasma corticosterone level 18.4 µg%). This difference in hypersensitivity to morphine-induced antinociception following adrenalectomy either in the morning or in the evening persisted for at least 2 weeks. Second, exposure to a novel environment (stress of a new cage) or administration of corticosterone (10 mg/kg body weight s.c.) prior to morning adrenalectomy decreased the sensitivity to morphine measured 1 week later. Third, RU 38486, a glucocorticoid antagonist, injected in the lateral cerebral ventricle prior to the evening adrenalectomy increased subsequent morphine antinociception. In attempts to understand the long-term effect on morphine antinociception, the opioid receptor sites were quantified by an in vivo procedure. Quantitative autoradiography of binding sites labeled after intravenous administration of a tracer dose of [3H]-diprenorphine showed a decrease in retention of the labeled opioid in cortical and midbrain regions of rats adrenalectomized in the evening when compared with rats operated in the morning. In conclusion, the data suggest that a neuroen-docrine state invoked by the actual plasma corticosterone level at the time of adrenalectomy has a long-lasting influence on the degree of post-adrenalectomy opioid-induced antinociception. These long-term alterations of opioid responsiveness are reflected in altered binding to the opioid receptor system in the brai

ISSN:0028-3835    

DOI:10.1159/000125046

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The hypothalamic arcuate nucleus plays an important role in the gating system controlling the secretion of hypothalamic neurons. In order to analyze this gating mechanism, arcuate neurons from rats aged 21–22 days were cultured in a chemically defined medium. Addition of nerve growth factor to this medium increased the survival of the arcuate neurons. Neuron characterization was done with the Lucifer Yellow liposome technique and neurofilament immunocytochemistry. Electrophysiological information was obtained with the patch-clamp technique by whole-cell recordings and single-channel measurements. This qualitative inventory demonstrated the presence of at least five types of conductances: a sodium conductance, two potassium conductances, a calcium-activated conductance, presumably determined by potassium, and a leakage conductanc

ISSN:0028-3835    

DOI:10.1159/000125047

出版商:S. Karger AG    

年代:1988

数据来源: Karger