ISSN:0028-3835    

DOI:10.1159/000126781

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Magnocellular neurons of the supraoptic (SON) and paraventricular (PVN) nuclei projecting to the neurohypophysis produce, in addition to the classical hormones vasopressin and oxytocin, a large number of other peptides, one of which is cholecystokinin (CCK). Binding sites for CCK have been identified in the posterior pituitary. Recently the cDNAs for CCKA and CCKB receptors were isolated and characterized, and CCKA and CCKB receptor mRNAs were localized in the SON and PVN. We have used complementary oligonucleotides and in situ hybridization histochemistry to study CCKB receptor mRNA in hypothalamic neurons. Changes in the expression of CCKB receptor mRNA in the SON and PVN were analysed in salt-loaded as well as in hypophysectomized animals. Levels of CCKB receptor mRNA in the PVN and SON increased markedly in salt-loaded animals as compared to controls. An increase in CCKB receptor mRNA levels was seen in the SON and PVN after 3 days of salt loading, with high levels continuing through 5 and 7 days. At 14 days, the levels of CCKB receptor mRNA in the PVN were significantly lower as compared to 7 days. Hypophysectomy 5 days prior to sacrifice, resulting in a nerve lesion in the neurohypophysial pathway and removal of the anterior pituitary hormones, induced a significant increase in CCKB receptor mRNA levels in neurons of the PVN. The increase in CCKB receptor mRNA labelling after salt loading was mainly observed in the ventrolateral part of the PVN and in the dorsolateral part of the SON, corresponding to oxytocin-containing neurons, whereas the increase after hypophysectomy was mainly seen in the central part of the PVN and in the ventral part of the SON, corresonding to vasopressin-containing neurons. The results suggest that the synthesis of CCKB receptors in magnocellular neurons is increased upon osmotic challenge and hypophysectomy.

ISSN:0028-3835    

DOI:10.1159/000126782

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

GABAA receptors mediate the inhibition of somatostatin gene expression and NMDA receptors mediate its stimulation. The aim of this study was to determine whether the two major neurotransmitters in the central nervous system (GABA and glutamate) could interact to control somatostatin mRNA content in primary cultures of hypothalamic neurons. Neurons were incubated for 15 min on days 3, 5, 7 or 11 of culture with Mg2+-free medium containing either NMDA (20 µM) or bicuculline (50 µM) to investigate the ontogenesis of somatostatin secretion in response to NMDA and GABA. We found that NMDA significantly elicited somatostatin release from day 3, and bicuculline-induced release was observed from day 5. An ontogenetic study of somatostatin mRNA levels revealed that it steadily increased up to day 5 (6-fold) and a slight but nonsignificant decrease was observed on day 7 which stabilized until day 13. Experiments were thus carried out on day 11 of culture. Pharmacological manipulations of the two types of receptors (NMDA and GABAA) were performed to study the effect of the interaction on somatostatin mRNA accumulation. Time-course studies revealed the optimal time of action of the neurotransmitters (20 h). Our results demonstrated that bicuculline-induced mRNA accumulation was not additive with that elicited by NMDA after 20 h of incubation. In contrast, (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d’)cyclohepten-510-imine hydrogen (MK-801) at 10 µM completely abolished the stimulatory effect of bicuculline during the same time period. In addition, muscimol was unable to decrease somatostatin mRNA levels when NMDA receptors were blocked by MK-801. These results suggest that bicuculline and NMDA-induced responses share at least one common step in the control of somatostatin mRNA le

ISSN:0028-3835    

DOI:10.1159/000126783

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

To examine the role of receptor changes in the adaptive response to physiological stimulation, the density and distribution of excitatory amino acid receptors within the hypothalamus and other brain regions were examined in rats deprived of water for 2 days. Membrane binding assay revealed an increase in glutamate receptor density and a small shift in the affinity of glutamate for the receptor. Regional analysis of these changes by receptor autoradiography specific for NMDA, non-NMDA or metabotropic glutamate receptor binding indicated that NMDA and metabotropic receptor densities are increased in the brain. Regional increases were found principally for the NMDA receptor binding within the supraoptic nucleus, anterior hypothalamus, caudate-putamen and globus pallidus with no significant changes in 24 other brain regions. No significant changes were found in any brain regions for AMPA receptors. Metabotropic and kainate receptors tended to parallel the NMDA receptor changes, although few regions reached statistical significance. These changes indicate that brain regions associated with water balance regulation show selective adaptive increases in NMDA receptors during water deprivation which may facilitate prolonged activation of these cells.

ISSN:0028-3835    

DOI:10.1159/000126784

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

A double-labeling immunofiuorescence procedure was used to determine whether progesterone receptor (PR)-containing neurons in the mediobasal hypothalamus of female guinea pig also contain neurotensin (NT). Animals were ovariectomized, primed by estradiol to induce PR and injected intracere-broventricularly with colchicine to visualize NT-immunopositive neurons. Approximatively 24% of the NT-immunoreactive (IR) neurons in the ventrolateral nucleus (VL) displayed PR immunoreactivity, accounting for 4% of the total population of cells containing PR in this region. The arcuate nucleus (AR) was observed to have both populations, but coexistence was rare. These findings provide neuroanatomical evidence that a subset of NT neurons is directly regulated by progesterone in the VL, a site that plays a key role in the control of female sexual behavior.

ISSN:0028-3835    

DOI:10.1159/000126785

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The biological effects of pituitary adenylate cyclase-activating peptide (PACAP) 27 and 38 on peptide secretion and gene regulation were studied in the mouse corticotrope-derived cell line AtT20. Treatment of these cells with PACAP 27/38 led to a dose-dependent increase in cAMP content and ACTH accumulation in the medium with an apparent ED50 value close to 10–9M The genomic effects of PACAP were first investigated by using a reporter gene containing a cAMP responsive element (CRE: TGACGTCA). PACAP 27/38 stimulate transcription from this construct and the effect is further increased when cells are cotreated with the phosphodiesterase inhibitor rolipram. Furthermore, we show by measuring nuclear heterologous proopiomelanocortin (POMC) RNA levels or by using a reporter gene containing the POMC promoter region, that PACAP stimulates POMC transcription. This transcriptional stimulation is mediated by the cAMP-dependent protein kinase (PKA) since genetic inactivation of PKA by a dominant inhibitory mutant of this enzyme completely abolished the effect of PACAP on POMC transcription. Finally, we show that the transcriptional stimulation of POMC by PACAP is repressed by the glucocorticoid receptor agonist dexamethasone. Taken together, these data suggest that PACAP is a hypophysiotropic hormone that exert similar if not identical functions as corticotropin-releasing hormone (CRH) on corticotrope cell

ISSN:0028-3835    

DOI:10.1159/000126786

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Arginine-vasopressin (AVP) is regarded as a potent stimulator of pituitary adrenocorticotropin (ACTH) secretion and participates therefore in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis function in concert with the physiological activator of the axis, hypothalamic corticotropin-releasing hormone (CRH). We examined the effects of AVP and/or three synthetic V1b receptor antagonists on the activity of the HPA axis in vivo and in vitro in the rat. AVP was injected intravenously to Sprague-Dawley rats (1 µg/rat) through an indwelling jugular catheter. AVP stimulated ACTH release, with maximal effect 10 min after injection. Intravenous injection of three V1b antagonists, [1-(β-mercapto-β, β-cyclopentamethylenepropionic acid),2-O-ethyltryrosine,4-valine] arginine vasopressin (d(CH2)s[Tyr(Et2)]VAVP (WK 1-1), 9-desglycine[1-(β-mercapto-β, β-cyclopentamethylenepropionic acid),2-O-ethyltyrosine,4-valine] arginine vasopressin desGly9d(CH2)5[Tyr(Et2)]-VAVP (WK 3-6), and 9-desglycine[1-(β-mercapto-β, β-cyclopentamethylene-propionic acid),2-D-(0-ethyl)tyrosine,4-valine] arginine vasopressin des Gly9d(CH2)5[D-Tyr(Et2)]VAVP (AO 3-21), prevented AVP-stimulated ACTH secretion. Explanted rat hypothalami incubated in vitro with graded concentrations of AVP (10-14-10-5M) secreted immunoreactive CRH (iCRH) in a concentration-dependent fashion. Maximal stimulatory effect occurred at the concentration of 10-6M. Incubation of hypothalami with WK 1-1, WK 3-6, or AO 3-21 (10-6M) prevented AVP-stimulated iCRH secretion. Results suggest that AVP plays a relevant, multiple role in the activation of the HPA axis in the rat. In fact, interactions between AVP and the pituitary corticotroph may not be solely due to a direct effect of AVP on ACTH secretion, but also to activation of the hypothalamic CRH neuron. These effects of AVP appear to be mediated by the V1b recepto

ISSN:0028-3835    

DOI:10.1159/000126787

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The effects of the reversible monoamine oxidaseA (MAOA) inhibitor moclobemide on the rat hypothalamic-pituitary-adrenocortical (HPA) axis were studied. The time-course experiments showed that moclobemide, given via the drinking water (4.5 mg/kg/day), produces significant decreases (p < 0.05) in adrenal weight after 5 (–23%) and 7 weeks (–16%) of treatment. It was found that long-term moclobemide treatment had neuroanatomically distinct effects on corticosteroid receptor expression. Hippocampal mineralocorticoid receptor (MR) levels were upregulated at 2 (+65%), 5 (+76%) and 7 (+19%) weeks of treatment. Glucocorticoid receptor (GR) levels in this limbic brain structure were slightly up-regulated by 10% at 5 weeks, and indistinguishable from controls after 2 and 7 weeks of treatment. After 5 weeks of treatment, MR levels were unchanged in the hypothalamus, and increased by 44, 24 and 28% in the neocortex, amygdala and anterior pituitary, respectively. GR concentrations were elevated by 24 and 14% in the hypothalamus and anterior pituitary, respectively, whereas neocortical and amygdaloid receptor levels were not altered. After 5 weeks of moclobemide treatment, marked decreases in [125I]Tyr0-ovine corticotropin-releasing hormone ([125I])-oCRH binding capacity and proopiomelanocortin (POMC) mRNA content were observed in the anterior pituitary. Regarding the functional implications of long-term anti-depressant treatment, moclobemide treatment (5 weeks, 4.5 mg/kg/day) significantly attenuated stress (30-min novel environment)-induced plasma ACTH (–35%) and corticosterone (–29%) levels; no changes were observed in basal plasma ACTH and corticosterone levels. In conclusion, this study shows that moclobemide has a concerted influence on multiple elements of the HPA axis manifesting functionally as a reduced neuroendocrine responsiveness to stress. In previous experiments, it was found that the structurally and pharmacologically distinct antidepressant amitriptyline after long-term administration also attenuated HPA axis activity. We postulate that an adjustement of HPA axis activity may be regarded as a common denominator for clinically efficacious antidepressan

ISSN:0028-3835    

DOI:10.1159/000126788

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Variations of serum prolactin (PRL) levels and activities of tuberoinfundibular dopaminergic (TIDA) neurons during the afternoon of ovariectomized (OVX) rats treated with or without estrogen were determined in this study. Long-term OVX rats treated with or without polyestradiol phosphate (0.1 mg/rat, s.c.) were decapitated every hour from 10.00 to 19.00h(except 11.00 and 13.00 h). Serum PRL and median eminence (ME) dihydroxyphenylacetic acid (DOPAC) or dihydroxyphenylalanine (DOPA) levels were determined by radioimmunoassay and high performance liquid chromatography plus electrochemical detection, respectively. A prominent PRL surge started and peaked around 14.00–15.00h, and remained significantly higher than levels of 10.00 and 12.00 h throughout the afternoon. Significant decreases of ME DOPAC and DOPA concentrations were also observed between 14.00 and 19.00 h. In OVX rats with no estrogen replacement, no PRL surge was observed and the changes of ME DOPAC concentrations during the afternoon were not significant except for that at 17.00 h. The ME DOPA accumulation, however, exhibited significantly lower levels from 14.00 to 19.00 h than that at 12.00 h, indicating that an endogenous rhythm for DA synthesis existed in OVX rats. In estrogen-treated OVX rats bearing bilateral lesions of the suprachiasmatic nuclei, both changes in serum PRL level and TIDA neuron activity were abolished. We conclude that an endogenous rhythm of the activities of TIDA neurons may exist in both OVX and OVX plus estrogen-treated rats. The rhythm is regulated by the suprachiasmatic nuclei and may be amplified by estrogen for the induction of PRL surg

ISSN:0028-3835    

DOI:10.1159/000126789

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Melatonin, a pineal hormone, is known to play an important role in mediating changes in the reproductive system which occur in response to seasonal changes in the length of the day. An in vitro pituitary perifusion system has been used to examine both direct and indirect effects of melatonin on pituitary gonadotropin basal secretion and responsiveness to GnRH stimulation. Anterior pituitaries from adult male golden hamsters were perifused with an APS 10 perifusion system for 6 h. Both basal secretion and secretion in response to hourly GnRH stimulation (1 min, 35 ng/ml pulses) were evaluated for LH and FSH. In order to expose pituitaries to shorter and longer durations of melatonin, tissue was perifused with melatonin-containing medium following dissection in the daytime (when endogenous melatonin levels are low) and following dissection in the nighttime (when endogenous melatonin levels are high). Exposure of pituitary tissue from golden hamsters to melatonin during perifusion caused a decrease in basal secretion of LH but did not affect GnRH stimulated LH or FSH release regardless of the time of dissection. There was, however, an effect of some diurnal factor to lower FSH responsiveness to GnRH stimulation from tissue dissected in the nighttime. It is suggested that melatonin may be responsible for this diurnal difference. Therefore, melatonin can act directly at the anterior pituitary to lower basal LH secretion, and melatonin or some other diurnal factor can act in vivo to lower pituitary FSH secretion in response to GnRH stimulation during the night.

ISSN:0028-3835    

DOI:10.1159/000126790

出版商:S. Karger AG    

年代:1994

数据来源: Karger