摘要:

The data presented here are the first to describe the distribution of estrogen receptor-β(ERβ)-like immunoreactivity in brain tissue. We employed an affinity purified rabbit antisemm made against a portion of the C-terminal of the ERβ protein. The majority of ERβ-like immunoreactive (ERβ-ir) neurons were found in the following regions: lateral septum, bed nucleus of the stria terminalis, paraventricular nucleus, supraoptic nucleus, medial amygdala, the dentate gyms and the CA1 and CA2 fields of the hippocampus. A few ERβ-ir neurons were noted in the anterior hypothalamus, periventricular nucleus, medial preoptic area, and in the arcuate nucleus. All of the immunoreactivity appeared nuclear in its subcellular distribution, with the exception of the cells in the lateral septum, CA1 and CA2. In these areas immunoreactivity was noted throughout the perikarya and in cell processes. The data suggest that ERβ mediates estrogen’s actions in a subset of hypothalamic and limbic

ISSN:0028-3835    

DOI:10.1159/000127221

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Since prostaglandins (PGs) and histamine (HA) seem to be involved in the activation of the hypothalamic-pituitary-adrenal axis following immunochallenges with lipopolysaccharide (LPS) endotoxin and cytokines, we investigated whether the histaminergic and eicosanoid systems in the male rat brain interact in their regulation of ACTH secretion. The PG synthesis inhibitor indomethacin (10 mg/kg i.p.) attenuated the ACTH response to LPS (10 µg/kg i.p.) and HA (30 µg i.c.v.). Infusion of PGE1, PGE2 or PGF2α (1 and/or 5 µg infused intracerebroventricularly) stimulated ACTH secretion. The ACTH response to PGEi was inhibited by the HA synthesis inhibitor α-fluoromethyl-histidine and the H1· receptor antagonist mepyramine (MEP) but not the H2 receptor antagonist cimetidine (CIM). Neither MEP nor CIM affected the ACTH response to PGE2. MEP and CIM attenuated the ACTH response induced by PGF2α. The findings indicate that HA and some PGs in the brain interact in their stimulatory regulation of ACTH secretion. Such an interaction may also be involved in their mediation of the ACTH response to immunochal

ISSN:0028-3835    

DOI:10.1159/000127222

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Previous studies in our laboratory suggest that neurotensin (NT) acts centrally to modulate adrenocorticotropin hormone (ACTH) and corticosterone release. In the present studies, we examined hypothalamic-pituitary-adrenal (HPA) function under basal conditions and during restraint stress following central administration of the highly specific NT receptor antagonist, SR48692. Chronic delivery of SR48692 to the paraventricular nucleus (PVN) of the hypothalamus via indwelling central cannulae attenuated both the diurnal- and stress-induced elevations in HPA activity. Thus, SR48692 decreased the diurnal increase in plasma ACTH and corticosterone during the evening phase of the cycle, but did not affect morning levels. Restraint-induced increases in plasma ACTH and corticosterone levels were also significantly reduced in the SR48692-implanted animals. This suggests that the inhibitory effects of SR48692 were restricted to periods of stimulated HPA activity. A decrease in corticotropin-releasing hormone (CRH)-like immunoreactivity was observed within the PVN following chronic SR48692, and parallel decreases in CRH-like immunoreactivity were observed within the external zone of the median eminence. These findings suggest that endogenous NT serves to increase HPA activity during periods of enhanced stimulation.

ISSN:0028-3835    

DOI:10.1159/000127223

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The corticotropin-releasing hormone (CRH) gene contains a perfect palindromic motif in its promoter region that allows binding of the cyclic adenosine monophosphate response element binding protein, CREB. Since previous studies suggest that the CRH gene can be activated by cyclic adenosine mono-phosphate, we determined whether stress and feedback inhibition by glucocorticoids in CRH-producing neurons in the hypothalamic paraventricular nucleus could be mediated by changes in the phosphorylation of CREB. Antisera to CREB and phospho-CREB Ser133 (PCREB), the active phosphorylated form of CREB, were used for immunohistochemical studies on rat brain. In nonstressed animals CREB immunostaining was confined to the nucleus of cells ubiquitously throughout the hypothalamus, while PCREB immunostaining was discretely localized in magnocellular neurons and only a few cells in the medial parvocellular subdivision of the paraventricular nucleus. Ether and handling stress markedly increased the number of PCREB-labeled neurons in the parvocellular subdivision. Double immunolabeling with CRH antiserum revealed that the majority of hypophysiotropic CRH neurons in stressed animals expressed PCREB. Following systemic administration of dexamethasone (100 µg/day) for 2.5 days, PCREB immunostaining was completely abolished in parvocellular CRH-producing neurons after ether or handling stress. Dexamethasone had no apparent effect on CREB immunostaining. These results demonstrate that glucocorticoids suppress CREB phosphorylation in hypophysiotropic CRH neurons and suggest that prevention of CREB phosphorylation is a possible mechanism for feedback inhibition of CRH biosynthesis by glucocorticoids

ISSN:0028-3835    

DOI:10.1159/000127224

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Catecholamines and neuropeptide Y (NPY) levels were determined in the adrenals of rats treated for 2.5 days with chlorisondamine (6 mg/day), a nicotinic ganglionic blocking agent, metyrapone (66 mg/day), an inhibitor of the 11 β-hydroxylase activity or both metyrapone and chlorisondamine. Chlorisondamine induced a significant increase in adrenal weight (31%) without significant rise in hypothalamic CRH content, plasma ACTH level and plasma corticosterone concentration. This drug was unable to affect significantly dopamine (DA), norepinephrine (NE) and epinephrine (E) content of the adrenals; in contrast, it induced a significant decrease (90%) of plasma NE and E levels. Chlorisondamine induced no change in adrenal NPY content as well as NPY mRNA level determined by Northern blot but significantly increased NPY plasma level. Metyrapone-treatment induced a significant drop of plasma corticosterone level and elicited a significant reduction of hypothalamic CRH content, a rise (460%) of the plasma ACTH concentration associated with a significant increase (18%) of the adrenal weight. A marked increase of DA (240%) and significant decrease of E (22%) in the adrenal gland were observed in response to metyrapone treatment. In addition, metyrapone induced a drop (23%) in plasma E level. In both the adrenals and the plasma, the ratio E/NE was significantly reduced by metyrapone treatment. Metyrapone elicited a significant increase of adrenal NPY content (88%) as well as of NPY mRNA revealed by Northern blot analysis but was unable to significantly affect NPY plasma level. The effects of chlorisondamine, given in combination with metyrapone on both hypothalamic CRH content and plasma ACTH level, were similar to those induced by metyrapone given alone. Chlorisondamine-mediated pharmacological ganglionic blockade increased metyrapone-induced adrenal hypertrophy and adrenal DA storage but prevented metyrapone-induced depletion of adrenal E as well as increase of the adrenal NPY mRNA level and NPY content. Chlorisondamine-induced elevation of plasma NPY level was not observed under metyrapone treatment. Present data suggest that the increase in adrenal NPY synthesis in response to metyrapone treatment is mediated by transsynaptic cholinergic activation and implies nicotinic receptors. On the other hand, adrenal TH may be regulated by additional or different mechanisms, which possibly involve nonnicotinic transmission. Present work also suggests that the suppression of the glucocorticoid feedback inhibition of hypothalamic CRH neurons could stimulate sympathoneuronal outflow and consequently elicit transsynaptic cholinergic activation of adrenal neuropeptide Y gene expression

ISSN:0028-3835    

DOI:10.1159/000127225

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In the amphibian Xenopus laevis, adaptation of the skin color to background light intensity is regulated by α-melanophore-stimulating hormone (α-MSH), a proopiomelanocortin (POMC)-derived peptide. In animals adapted to a white background, the level of POMC biosynthesis in the intermediate pituitary is much lower than in animals adapted to a black background. Release of α-MSH from neurointermediate lobes of white-adapted animals is stimulated in vitro by the regulatory peptides sauvagine and thyrotropin-releasing hormone (TRH), which are produced in the magnocellular nucleus of the hypothalamus. To study the role of sauvagine, cAMP, TRH and phorbol 12-myristate 13-acetate (PMA) in the regulation of POMC biosynthesis, the degree of incorporation of radioactive amino acids into the POMC protein was determined after treatment of the neurointermediate lobes with these secretagogues. When lobes of white-adapted animals are incubated in vitro, biosynthetic activity spontaneously increases because hypothalamic inhibitory control is removed by dissection. In addition to this control situation, the effects of secretagogues were tested on lobes with an inhibited level of biosynthesis, which is achieved by addition of neuropeptide Y (NPY) to the incubation medium. After 24 h of treatment, TRH stimulated POMC biosynthesis in NPY-inhibited lobes of white-adapted animals from 40.2 to 95.3% of control level. This stimulation could not be reduced by adding PMA, which indicates that protein kinase C is not involved in the stimulation of POMC biosynthesis by TRH. Sauvagine partially restored POMC biosynthesis from 27.2 to 62.5% of control level, whereas 8-Br-cAMP completely counteracted NPY inhibition from 27.8 to 97.5% of control level. After 3 days of treatment, stimulation by sauvagine and 8-Br-cAMP was maintained (sauvagine increased POMC biosynthesis in NPY-inhibited lobes from 7.4 to 36.2% of control level and 8-Br-cAMP stimulated from 6.5 to 82.5% of control level). TRH had no effect on POMC biosynthesis after 3 days of treatment, although its receptor was still functional as was shown in superfusion experiments where TRH stimulated α-MSH secretion. The observations indicate that the neuropeptides sauvagine and TRH differently control POMC biosynthesis in the Xenopus intermediate pituitary. This differential regulation is not only apparent with regard to time aspects (sauvagine has a sustained regulatory function, whereas TRH is only effective in the initial phase of POMC biosynthesis stimulation), but also an uncoupling of biosynthetic and release processes could be shown for TRH, which did not occur with sauvag

ISSN:0028-3835    

DOI:10.1159/000127226

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Electrochemical and electrical stimulation of the medial preoptic area (MPA) was shown to induce release of LH in rats. Owing to differences in cytoarchitecture and neural afferents between the medial (mMPA) and lateral (IMPA) parts of the MPA, we decided to explore whether this difference in organization would distinctly influence the secretion of gonadotropin. Both parts of the MPA were electrochemically stimulated on the day of proestrus in freely behaving rats bearing chronic implanted electrodes. An anodic direct current of 100 µA was delivered for 40 s at 11.00 h and blood samples were obtained every hour until 17.00 h. Serum LH concentrations in rats stimulated in the medial part of the MPA showed a robust rise 1 h after the stimulus was applied and the values remained high up to the end of the bleeding period. All these animals ovulated. An initial rise in serum LH was also seen in rats stimulated in the IMPA but serum values thereafter returned to basal levels, significantly lower than those in the mMPA-stimulated or in control, nonstimulated rats. Only 2 rats showed full ovulation and the others failed to ovulate or had partial ovulation. Injection of the serotonin antagonist, methysergide, did not affect the response of rats stimulated in either the mMPA or IMPA. The GABA antagonist, bicuculline, had no effect on LH release evoked by IMPA stimulation but blocked the release induced by mMPA stimulation. This later blockade was partially reversed by the administration of the opioid receptor antagonist, naloxone, suggesting the existence of GABA facilitatory influences on LH release via inhibition of opioidergic inputs to the GnRH neurons. On the other hand, naloxone administration had no effect on LH release evoked by stimulation of the mMPA but partially reversed the inhibition resulting from stimulating the IMPA. These data indicate that the mMPA and IMPA have opposite effects on LH secretion and provide evidence for the possible neurotransmitters involved

ISSN:0028-3835    

DOI:10.1159/000127227

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0028-3835    

DOI:10.1159/000127228

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Excitatory amino acids, particularly glutamate, are thought to be important for the maturation of the brain-pituitary-gonadal axis and the induction of puberty in the rat. We have previously shown that, in the female rat, GnRH neurons preferentially express the KA2 and NMDAR2A receptor subunit mRNAs, but not AMPA or NMDAR1 mRNA. The aim of the present study was to determine whether the onset or rate of KA2 and NMDAR2A receptor expression in GnRH neurons is correlated with the onset of puberty. Dual in situ hybridization using digoxigenin-labeled GnRH cRNA probes and 35S-labeled glutamate receptor subunit probes, followed by autoradiography and image analysis were used to measure the KA2 or NMDAR2A mRNA content in GnRH neurons in 20- to 50-day-old female rats which were sacrificed at 08.00 or 17.00 h. The results show that: (a) the KA2 mRNA content of GnRH neurons and the number of GnRH neurons expressing KA2 mRNA increase progressively in the morning hours between postnatal days 20 and 40; (b) the diurnal pattern of KA2 mRNA levels in GnRH neurons changes between days 40 and 50 from high KA2 levels in the morning hours before day 40 to high KA2 mRNA levels in the afternoon in 45- and 50-day-old animals; (c) while the high levels of KA2 mRNA in GnRH neurons in the morning hours of 20-to 40-day-old animals are paralleled by an overall increase in KA2 expression in the preoptic area, the rise in KA2 mRNA in GnRH neurons in the afternoon of 45- and 50-day-old animals appears to be specific for the GnRH neurons, and (d) no significant differences were detected for the NMDAR2A mRNA content in GnRH neurons among the different age groups and the morning and afternoon values. Since the gradual increase in the KA2 mRNA content in GnRH neurons of animals reaching puberty as well as the reversal of diurnal rhythmicity in KA2 receptor mRNA content of GnRH neurons coincide with the times of vaginal opening and first ovulation, it is suggested that glutamate, acting through KA2 receptors directly on GnRH neurons is, at least in part, an important factor in the excitatory regulation of the postnatal sexual development of the female rat. In contrast, expression of the NMDA-preferring receptor, NMDAR2A, in GnRH neurons appeared to be unchanged during this development.

ISSN:0028-3835    

DOI:10.1159/000127229

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

In addition to its traditional role as a circulating vasoactive peptide, vasopressin (VP) has been shown to play significant roles in central cardiovascular processing. The recent description of VP receptors within the subfomical organ (SFO) has suggested this circumventricular organ (CVO) as a potential locus for feedback actions of circulating VP on the brain. The well-established anatomical connections between SFO and hypothalamic autonomic control centers provide further arguments in support of such a view. This study was undertaken to determine the physiological consequences of activation of VP receptors within the SFO of urethane anesthetized rats. Micro injection (0.5 µl) of 5 pmol VP into SFO resulted in significant decreases in blood pressure (BP, mean AUC-638.3 ± 110.3 mm Hg·s, p 0.05, n = 9). In contrast to the former depressor effects, VP microinjection (5 pmol in 0.5 µl) into the third ventricle produced large increases in BP (mean AUC 1,461.8 ± 368.97 mm Hg·s, p 0.05, n = 6). The hypotensive effects observed in response to VP microinjection into SFO were abolished by systemic treatment with a V1 0.05) compared to BP response before V1 receptor blockade (mean AUC -605.9 ± 119.8 mm Hg·s, n = 4). These results suggest that the SFO may be an essential structure in the feedback control loop through which circulating VP influences descending autonomic pathways involved in cardiova

ISSN:0028-3835    

DOI:10.1159/000127230

出版商:S. Karger AG    

年代:1997

数据来源: Karger