摘要:

Thyrotropin-stimulating hormone (TSH) and prolactin (PRL) responses to an acute oral challenge of fenfluramine (60 mg), a central serotoninergic (5-hydroxytryptamine) releasing/uptake inhibiting agent, were examined in 8 healthy males in order to assess the role of central serotoninergic stimulation in the release of TSH. Plasma PRL, but not TSH, was significantly elevated by fenfluramine. These data suggest that central serotoninergic activity does not play an important role in the physiologic release of plasma TSH in man. Further, thyrotropin-releasing hormone is unlikely to be the PRL-releasing factor involved in the fenfluramine-induced stimulation of PRL.

ISSN:0028-3835    

DOI:10.1159/000124924

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

In this study we have evaluated a possible role for brain serotoninergic neurons in the regulation of vasopressin secretion using pharmacological methods. In order to accomplish this, we have developed a specific and sensitive vasopressin radioimmunoassay along with a highly reproducible plasma extraction protocol. These tools were used to evaluate the plasma vasopressin response to several pharmacological challenges in conscious rats. Treatment with the serotonin (5-HT) releaser p-chloroamphetamine caused a significant increase in plasma vasopressin concentration. This effect was blocked by posterior hypothalamic deafferentation which separates serotonin cell bodies in the midbrain from their nerve terminals in the hypothalamus. Administration of graded doses of several 5-HT1 agonists had no effect. However, treatment with MK212, a serotonin agonist with 5-HT1 + 5-HT2 activity, induced a significant increase in plasma vasopressin concentration. The effect of MK212 on plasma vasopressin was completely abolished by the selective 5-HT2 receptor blocker LY53857. These studies confirm and extend studies by others that provide pharmacological evidence for serotoninergic regulation of vasopressin secretion via a selective 5-HT2 receptor mechanism. The specific neuroanatomical site(s) where serotonin exerts this effect are unknown, and the physiological consequences of these studies remain to be established.

ISSN:0028-3835    

DOI:10.1159/000124925

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Immunohistochemical studies have identified immunoreactive prolactin (IR-PRL) in the hypothalamus and other areas of the rat brain. However, immunocytochemical techniques make it difficult to quantify the amount of antigen localized in a specific region. In this study, IR-PRL was extracted from selected regions of the rat brain, consisting of the median eminence, dorsal and ventral hypothalamus, thalamus, amygdalae, cerebellum, cortex, hippocampus, septum, pons-medulla, and olfactory lobes, and the concentrations of IR-PRL were determined by radioimmunoassay. Whereas IR-PRL was detected in all brain regions in both the male and the female rat brain, the concentrations of IR-PRL in the female rat were significantly greater than those measured in the corresponding region of the male rat brain. In the female rat, hypophysectomy significantly reduced, but did not eliminate, the concentration of IR-PRL in hypothalamus, amygdala, thalamus, and pons-medulla. In contrast, hypophysectomy did not affect the concentration of IR-PRL in any brain regions of the male rat. Injection of colchicine into the lateral ventricle decreased the concentration of IR-PRL in the median eminence and increased the concentration of IR-PRL in the ventral hypothalamus in male and female rats. In addition, extracted hypothalamic and pituitary IR-PRL displayed similar dilution curves in the PRL assay and elution patterns on Sephadex G-100. These data indicate that both the male and the female rat brain contains an IR-PRL-like material with physicochemical properties similar to those of pituitary PRL. This material is differentially distributed in the male and female brain and is found in greater concentrations in the female brain. Finally, the maintenance of IR-PRL in the brain in hypophysectomized rats and the decrease in median eminence IR-PRL in colchicine-treated rats suggest that this IR-PRL-like material is synthesized in the central nervous system.

ISSN:0028-3835    

DOI:10.1159/000124926

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The significant relationship of drinking to brain opioid receptors was determined using naloxone, a preferential antagonist of opioid µ receptor, in water-deprived rats. Whereas 48-hour food deprivation did not affect naloxone binding in any brain regions, 48-hour water deprivation caused a significant decrease in naloxone binding in the striatum, but not in the other brain regions. The striatal naloxone binding was found to progressively decrease with a period (0–48 h) of water deprivation. No significant change in naloxone binding in the hypothalamus or midbrain was observed during water deprivation. Water deprivation did not change the affinity constant of naloxone binding in the striatum. These observations indicate that the change in the striatal opioid receptors was specifically associated with thirsty sensation in the r

ISSN:0028-3835    

DOI:10.1159/000124927

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The in vitro effects of estrogens, progestins, and their related analogs on muscarinic receptor binding sites were studied in the hypothalamic membranes prepared from ovariectomized rats. The binding assays were performed under a nonequilibrium condition. Progestins and their metabolites were active in inhibiting the binding of [3H](-)QNB to muscarinic receptors, whereas estrogenic compounds were devoid of this effect. Progesterone was also found to be active in inhibiting the binding of [3H](-)QNB to pituitary membranes. The IC50 values of progesterone and its metabolite, 17α-hydroxyprogesterone, were 34 and 24 µM, respectively. The inhibitory effect of progesterone was rapid, reversible, and not dependent on divalent metal ions (Ca2+, Cu2+, Fe2+, Mg2+, Mn2+, and Zn2+). Analyses of the binding data with Scatchard and Lineweaver-Burke plots revealed that progesterone significantly increased the apparent Kd of muscarinic receptor binding sites from 0.54 (SE= ± 0.08) nM to 2.44 (SE= ± 0.49) nM in hypothalamic membranes and from 0.21 (SE= ± 0.03) nM to 0.34 (SE= ± 0.03) nM in pituitary membranes without a significant effect on the receptor density in both membrane preparations. Progesterone decreased the rate of association of [3H](-)QNB with muscarinic receptors without a significant effect on its rate of dissociation from the [3H](-)QNB-receptor complex. These results indicate that progesterone, but not estrogenic compounds, was capable of interacting with hypothalamic and pituitary muscarinic receptors in

ISSN:0028-3835    

DOI:10.1159/000124928

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Several lines of experimental evidence suggest that acetylcholine (ACh) is excitatory to the hypothalamic-pituitary-adrenal (HPA) axis. Since previous experiments have shown that ACh does not affect pituitary adrenocorticotropin secretion in vitro, we hypothesized that ACh stimulates the HPA axis by causing hypothalamic corticotropin-releasing hormone (CRH) secretion. We examined this hypothesis using an organ culture system that measures the ability of single rat hypothalami to secrete immunoreactive CRH (IR-rCRH) in vitro. ACh stimulated hypothalamic IR-rCRH secretion in a dose-dependent fashion, at concentrations ranging from 3.3 × 10–10 to 10–5M. This effect was antagonized by the simultaneous presence of atropine and hexamethonium, a muscarinic and a nicotinic receptor antagonist, respectively (p < 0.05). Further evidence for the cholinergic regulation of the CRH neuron was provided by the findings that both carbachol, a muscarinic receptor agonist, and nicotine, a nicotinic receptor agonist, stimulated IR-rCRH secretion in a dose-dependent fashion. These effects were antagonized by atropine and hexamethonium, respectively, suggesting that both muscarinic and nicotinic receptors are involved in the process. ACh stimulated hypothalamic IR-rCRH secretion in the presence of phentolamine, an α-adrenergic antagonist, and ritanserin, a serotonin receptor antagonist, suggesting that the cholinergic stimulation of CRH secretion is not mediated by α-adrenergic or serotonergic interneurons. We conclude that ACh stimulates hypothalamic CRH secretion via both muscarinic and nicotinic receptor mechanisms. This effect is not mediated by a serotonergic or α-adrenergic interneuron. These data suggest that ACh may be implicated in the regulation and the stress activation of the HPA axis

ISSN:0028-3835    

DOI:10.1159/000124929

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The effect of constant light and constant dark on the circadian rhythm of the concentrations of hypothalamic corticotropin-releasing-factor-like immunoreactivity (CRF-LI), plasma ACTH, and corticosterone was investigated. Groups of rats were maintained under normal light-dark, constant light, or constant dark conditions for 10 days. Rats were then killed over a 24-hour time period and hypothalamic CRF-LI, plasma ACTH, and corticosterone concentrations were determined by radioimmunoassay. Under normal light-dark conditions, troughs in hypothalamic CRF-LI concentrations coincided with peaks in plasma ACTH and corticosterone concentrations. In rats housed under constant dark conditions for 10 days, higher hypothalamic CRF-LI concentrations were detected at 20.00, 24.00 and 04.00 h than at 08.00, 12.00 and 16.00 h. These relatively high hypothalamic CRF-LI concentrations coincided with relatively low plasma ACTH concentrations. The amplitude of plasma ACTH concentrations was markedly attenuated compared to levels of rats housed under normal light-dark conditions. The rats exposed to constant dark continued to demonstrate higher plasma corticosterone concentrations post meridiem than ante meridiem. The peak in plasma corticosterone coincided with the peak in plasma ACTH concentrations; however, the amplitude was normal. In rats maintained in constant light for 10 days, a decrease in hypothalamic CRF-LI concentrations at 20.00 h coincided with a peak in plasma ACTH. The peak in plasma ACTH concentrations was not associated with a peak in plasma corticosterone concentrations. The rhythm of plasma corticosterone concentrations was dramatically attenuated and phase-shifted. Together, these findings indicate that alterations of normal light-dark conditions result in changes in the circadian variation in hypothalamic CRF-LI, plasma ACTH, and corticosterone concentrations. Changes in the circadian rhythm of plasma ACTH concentrations were related to changes in the rhythm of hypothalamic CRF-LI, but an apparent dissociation between the pituitary and adrenal rhythms was observed.

ISSN:0028-3835    

DOI:10.1159/000124930

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Lipotropin and peptides related to β-endorphin were extracted from the anterior pituitary and the pars intermedia of porcine pituitary and were resolved by gel exclusion and ion exchange chromatography. Possible heterogeneity in the structure of the lipotropin was investigated by identifying the C-terminal fragment released by limited proteolysis with trypsin; the cleavage was restricted to the carboxyl group of arginine residues by employing citraconylation to protect the ε-NH2 groups of lysine. The lipotropin obained from both regions of the pituitary gave rise to the same C-terminal peptide which contained the 31-residue sequence of β-endorphin; none of the 26- and 27-residue forms was detected. In contrast, the β-endorphin-related peptides that were isolated directly from the pars intermedia exhibited a high degree of C-terminal proteolysis: they were present principally as the 26- and 27-residue peptides. The results demonstrate that lipotropin differs from β-endorphin in that it occurs exclusively in the form that contains the full C-terminal sequence. It is concluded that during biosynthesis lipotropin undergoes conversion to β-endorphin before proteolysis takes place at the C-terminus. The processing reactions that convert lipotropin to β-endorphin 1–31 and β-endorphin 1–31 to β-endorphin 1–27 are thus ordered and not competitive. The results also indicate that glycylglutamine, the bioactive C-terminal dipeptide of lipotropin, is formed from β-endorphin and not f

ISSN:0028-3835    

DOI:10.1159/000124931

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Arachidonic acid and its lipoxygenase products may contribute to the process of prolactin (PRL) release. In the present study we investigate the role of 15-hydroperoxyeicosatetraenoicacid (15-HPETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) on PRL secretion from GH3 cells. The incubation of GH3 cells with the lipoxygenase product 15-HETE significantly increased PRL release in a concentration-dependent manner. Nordihydroguaiaretic acid (NDGA), which reduces the production of arachidonate metabolites via the lipoxygenase pathway, also reduced basal and TRH or arachidonic-acid-stimulated-PRL release. The inhibitory effect of NDGA on PRL release could be overcome by the addition of 15-HETE. The time course curve of PRL release from cells challanged by 15-HETE had the same profile as that of cells stimulated by TRH. The stimulating effect of 15-HPETE (ED50 = 0.7 × 10–9M), which is the direct precursor of 15-HETE, on PRL release was greater than TRH or 15-HETE (ED50 M). Furthermore 15-HPETE and 15-HETE seemed to affect the release of newly synthesized PRL. These data indicate that 15-HETE and 15-HPETE could be important intracellular components in the control of PRL secretion and may account for at least a part of arachidonate-induced PRL release from

ISSN:0028-3835    

DOI:10.1159/000124932

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The quantitative autoradiographic deoxyglucose method was used to study the effects of acute adrenalectomy on local cerebral glucose utilization in conscious albino rats. Five hours following removal of the adrenal glands, glucose utilization was increased (4–55%) throughout the brain, particularly in the locus ceruleus, hypothalamic paraventricular nucleus, hippocampus, median eminence and anterior lobe of the pituitary gland. These structures are involved in the regulation of corticotropin-releasing factor, vasopressin, and adrenocorticotropic hormone. Treatment with dexametha-sone (0.25 mg/kg i.m.) substantially reduced or prevented the stimulatory effects of adrenalectomy on cerebral glucose metabolism. These results demonstrate: (1) the existence of a negative feedback loop between the brain and adrenal glands in which corticosteroids exert an inhibitory action on glucose utilization of brain regions participating in adrenotropic regulation, and (2) a general inhibitory action of glucocorticoids on cerebral metabolis

ISSN:0028-3835    

DOI:10.1159/000124933

出版商:S. Karger AG    

年代:1988

数据来源: Karger