摘要:

Serotonin (5-HT) appears to be involved in the central control of the prolactin (PRL) response to suckling and estrogen. Furthermore, 5-HT may participate in the mediation of stress-induced PRL release. In order further to elucidate the role of 5-HT and the type of 5-HT receptor(s) involved in the PRL response to stress, we investigated the effect of blockade of 5-HT1, 5-HT2 or 5-HT3 receptors on the restraint or ether stress-induced release of PRL in male rats. Pretreatment with the 5-HT1 + 2 receptor antagonist methysergide (0.5 or 2.5 mg/kg i.p.) inhibited or prevented the PRL response to restraint or ether stress. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (0.5 or 2.5 mg/kg i.p.) inhibited the response to restraint or ether stress approximately 30 or 60%, respectively. Higher doses of both 5-HT2 receptor antagonists (10 mg/kg i.p.) had a minor inhibitory effect (5-30% for ketanserin and 50% for LY 53857). Prior intraperitoneal administration of the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the restraint stress-induced PRL release dose-dependently. Both compounds inhibited the PRL response to ether stress, but only the effect of GR was dose-related. The maximal inhibitory effect (70% inhibition of the PRL response to restraint or ether stress) was obtained for both compounds at a dose of 0.1 mg/kg. We conclude that serotonergic neurons are involved in the mediation of the stress-induced PRL release by activation of 5-HT1, 5-HT2 as well as 5-HT3 receptors.

ISSN:0028-3835    

DOI:10.1159/000126251

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Estradiol valerate (EV) treatment in the rat induces a lesion of the hypothalamic arcuate nucleus, resulting in significant decreases in hypothalamic β-endorphin. In addition, the EV treatment causes a selective increase in µ-opioid binding in the medial preoptic area (MPOA). Since β-endorphin neurons located in the arcuate nucleus project extensively to the MPOA, we have hypothesized that the EV-induced loss of these afferents induces a compensatory upregulation of µ-opioid receptors in opioid target neurons. In order to test this hypothesis, we have utilized monosodium glutamate (MSG) treated animals as a model of β-endorphin cell loss and hence of β-endorphin deafferentation of the MPOA. Neonatal MSG treatment has been shown to result in the destruction of 80-90% of arcuate neurons accompanied by pronounced decreases in β-endorphin concentrations in both arcuate nucleus and MPOA. µ-Opioid binding sites were radioautographically labeled in sections from the MPOA of sham- and MSG-injected animals using the methionine enkephalin analogue 125I-FK 33-824 and quantitated by computer-assisted densitometry. The remainder of the hypothalamus of these same animals was utilized for the determination of the β-endorphin concentration. The hypothalami of rats treated with MSG exhibited 62% (p < 0.01) less β-endorphin than saline-injected controls. In addition, the mean µ-opioid-binding densities in the MPOA were 24% (p < 0.05) above controls in the MSG-treated group. Linear regression analysis of hypothalamic β-endorphin concentrations and µ-opioid-binding densities within the same animals yielded an inverse proportional relationship with a coefficient of correlation of-0.85 and a goodness of fit of 0.7. These results substantiate the hypothesis that EV-induced destruction of β-endorphin neurons in the arcuate nucleus may result in chronic µ-opioid receptor upregulation in the MPOA and further suggest that β-endorphin may regulate µ-opioid receptor dens

ISSN:0028-3835    

DOI:10.1159/000126252

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The stimulatory effect of dopamine (DA) on the release of oxytocin (OT) in lactating rats is exerted at the D-1 DA receptor subtype. Because the neural loci mediating this effect have not been identified, the objective of the present studies was to test whether OT release in the lactating rat would be elevated after central administration of a D-1 DA receptor agonist into the third ventricle (3V) or directly into either the rostral paraventricular/anterior commissural nucleus area (PVN/ACN), the central paraventricular nucleus area, or the supraoptic nucleus (SON), all of which contain OT neurosecretory cells. Lactating rats were implanted with a stainless steel cannula directed into one of the above areas or into the arcuate-ventromedial region of the medial basal hypothalamus (MBH), or sites dorsal to the PVN/ACN or SON, which served as anatomical controls. After 6-7 days of recovery, each animal received an intra-atrial cannula for sequential blood sampling, and was used in experiments 24 h later. Animals were separated from their litters, and following a period of basal blood sampling, received central microinjections of either vehicle, the D-1 DA receptor agonist SKF-38393, or the D-2 DA receptor agonist quinpirole, and blood samples were removed periodically for 60 min. An injection of angiotensin II (Ang II, 100 ng) was made into each site as a positive control for OT release. Injection of SKF-38393 (12.5 or 50 µg/5 µl) into the 3V resulted in a statistically significant and dose-releated increase in plasma OT concentrations, which was attenuated by intravenous pretreatment with the specific D-1 DA receptor antagonist, SCH-23390 (1.2 mg/kg). Unilateral injection of SKF-38393 (8 µg) into the SON region also produced a significant increase in plasma OT concentrations, while more modest increases followed injection of this agent into the PVN sites. Systemic pretreatment with the D-1 DA antagonist also blocked the effect of SKF-38393 in the SON. Plasma OT concentrations were not significantly changed after administration of SKF-38393 into the MBH or to dorsal control sites, or after any central injections of vehicle or the D-2 agonist quinpirole. Ang II markedly stimulated OT release after administration to 3V, PVN, SON and MBH, but not to the control sites dorsal to the PVN and SON. The present findings extend previous observations that D-1 DA receptors mediate the central dopaminergic stimulation of OT secretion in the lactating rat, and suggest that the SON region may be an important locus for this effe

ISSN:0028-3835    

DOI:10.1159/000126253

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Reflexive ovulation in the rat, induced by caesarian section performed on day 22 of pregnancy, was blocked by prior bilateral transection of the pelvic and/ or hypogastric nerves, which convey afferent activity from the reproductive tract. Tubal ova and hemorrhagic ovarian follicles were counted 24 h after bilateral nerve transections or sham neurectomy. Whereas the median numbers of ova and hemorrhagic follicles in the sham neurectomy group were 4.5 and 3.5, respectively, these values in each of the neurectomy groups were 0. The present findings indicate that caesarian section activates the pelvic and hypogastric nerves to trigger ovulation. This suggests that normally the rat is a spontaneous ovulator during the estrous cycle (nonpregnancy) phase of its reproductive cycle, and may become a reflexive ovulator at the parturient phase of its reproductive cycle.

ISSN:0028-3835    

DOI:10.1159/000126254

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Lactotrophs have several different kinds of receptors, such as dopaminergic D2, somatostatin, angiotensin II and thyrotropin-releasing hormone receptors, which stimulate or inhibit prolaction release. We have studied the specificity of phenoxybenzamine on receptors in lactotrophs. Phenoxybenzamine is a β-haloalkylamine which alkylates chemically active radicals such as hydroxy, sulfhydryl, and amino groups. This alkylation is an irreversible chemical reaction in contrast to the receptor-secretagogue complex which is present in a state of dynamic equilibrium. Primary cultured rat adenohypophyseal cells were used in this study. A dose-response relationship was examined between concentrations of phenoxybenzamine pretreatment and prolactin release using a monolayer cell culture system. The inhibitory action of dopamine (10 µmol/l) on the control group (13.0 ± 0.1 ng/ml or 86% inhibition relative to the control) was significantly higher than on the 0.1-µmol/l phenoxybenzamine-pretreated group (39.0 ± 0.2 ng/ml or 58% inhibition relative to the control), but the stimulatory effect of thyrotropin-releasing hormone on prolactin release was not significantly affected up to a 10-µmol/l phenoxybenzamine pretreatement as compared with the control group. We thus selected a phenoxybenzamine concentration of 0.1 µmol/l for the next series of perifusion experiments in order to examine dynamic changes in prolactin release. The basal prolaction release was decreased to almost half by phenoxybenzamine pretreatment. The inhibitory action of dopamine (0.1 µmol/l containing 0.1 mmol/l ascorbic acid) was significantly less in the phenoxybenzamine-pretreated group (68% of the basal prolactin concentration) than in the control group (31% of the basal concentration). However, the relative actions of somatostatin, thyrotropin-releasing hormone, angiotensin II, and dibutyryl adenosine 3’,5’-cyclic adenosine monophosphate were not significantly affected by the phenoxybenzamine pretreatment. These observations suggest that phenoxybenzamine is relatively selective to dopaminergic D2 receptors in primary cultured lactotrophs. The basal prolactin release in the phenoxybenzamine-pretreated group increased steadily during the experimental period. The basal prolactin release was doubled within 153.7

ISSN:0028-3835    

DOI:10.1159/000126255

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effect of a high concentration of catecholamines on phenoxybenzamine pretreatment was examined. The efficacy of the pretreatments was monitored by testing the inhibitory action of dopamine on prolactin release. Phenoxybenzamine is a β-haloalkylamine which alkylates and irreversibly inactivates adrenergic α-receptors in smooth muscle. Dopaminergic D2 receptors share several common characteristics with the α-receptors. Primary cultured male rat pituitary cells were used. After phenoxybenzamine (0.1 µmol/l) pretreatment, the inhibitory action of dopamine on prolactin release was significantly reduced in a perifusion system. When the cells were pretreated with phenoxybenzamine in medium containing 0.1 or 1 mmol/l dopamine, the 0.1-mmol/l dopamine did not change the effect of phenoxybenzamine on inactivation of the receptors, but the 1-mmol/l dopamine eliminated the effect of phenoxybenzamine pretreatment. These observations were confirmed with a static monolayer culture system. The observations illustrate that a high concentration of dopamine forms a D2 receptor-dopamine complex and protects the D2 from inactivation by phenoxybenzamine. When the cells were pretreated with 0.1 µmol/l phenoxybenzamine in a medium containing 1 mmol/l epinephrine, the effect of the phenoxybenzamine was also eliminated, suggesting that a sufficient amount of D2 receptor-epinephrine complex was formed to protect the receptor from inactivation. The hormone release in response to a secretagogue depends on its affinity and intrinsic activity. It is, therefore, suggested that the intrinsic activity of epinephrine is much lower than that of dopamine on prolactin release, since the D2 receptor-epinephrine complex is as stable as the D2 receptor-dopamine complex, and the inhibitory action of epinephrine on prolactin release is less than 10% of that of dopamine. This study is the first to demonstrate that a high concentration of dopamine or epinephrine indeed forms receptor-ligand complexes and protects the D2 receptor from inactivation by phenoxybenzamine in endocrine c

ISSN:0028-3835    

DOI:10.1159/000126256

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Insulin-deficient states are associated with an impaired function of the hypothalamic-pituitary-gonadal axis, but the mechanisms underlying hypothalamic alterations in experimental diabetes are still unknown. We investigated the effect of glucose concentrations, in the presence and absence of insulin, on LHRH release from perifused hypothalamic fragments from female adult ovariectomized rats. Glucose and insulin were added to the perifusion medium (Earle’s, pH 7.4, gassed with 95% O2/5% CO2, flow rate 50 µl/min). When glucose was absent (in the presence of insulin 10 mU/1), LHRH release was reduced, peak levels being <5 pg/100 µl. The addition of glucose (100 and 300 mg/dl), in the absence of insulin, resulted in peak LHRH levels fluctuating around 35 pg/100 µl (p < 0.05 vs. glucose 0 mg/dl). When glucose (100 or 300 mg/dl) and insulin (10 mU/1) were combined, an eightfold increase in peak LHRH values was observed, and peak levels reached 300 pg/ 100 µl (p < 0.05 vs. glucose 100 and 300 mg/dl alone). In conclusion, LHRH release by perifused hypothalamic fragments is dramatically increased by low concentrations of insulin; this occurs only when glucose is available. Acutely elevated glucose levels (from 100 to 300 mg/dl) do not affect LHRH re

ISSN:0028-3835    

DOI:10.1159/000126257

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Histamine (HA) stimulates the release of the pro-opiomelanocortin (POMC)-derived pep-tides ACTH, β-endorphin (β-END), β-lipotropin and α-melanocyte-stimulating hormone, and HA is involved in the mediation of the stress-induced release of these peptides. The effect of HA is indirect and may involve the hypothalamic regulating factors, corticotropin-releasing hormone (CRH) and/or arginine-vasopressin (AVP). We studied the effect of immunoneutralization with specific antisera against CRH or AVP on the response of ACTH and β-END to HA, restraint stress, CRH, AVP or a posterior pituitary extract in male rats. Intracerebroventricular infusion of HA (34-540 nmol) increased the plasma levels of ACTH and β-END immunoreactivity (β-ENDir) in a dose-dependent manner. Pretreatment with antiserum to CRH or AVP prevented the ACTH response to 270 nmol HA and inhibited the β-ENDir response by 30-60%. One to five minutes of restraint stress caused an increase in the plasma levels of ACTH and β-ENDir. The increase was dependent on the duration of stress exposure. Pretreatment with CRH antiserum abolished the ACTH response to 5 min of restraint stress and inhibited the β-ENDir response by 60%. Immunoneutralization with AVP antiserum had only half the inhibitory effect of that seen with CRH antiserum. CRH (100 pmol i.v.) increased the plasma levels of ACTH and β-ENDir. This effect was abolished by pretreatment with CRH antiserum, whereas pretreatment with AVP antiserum prevented the CRH-induced ACTH release and inhibited the β-ENDir response by 50%. AVP (24-800 pmol i.v.) stimulated ACTH and β-ENDir in a dose-dependent manner. CRH and AVP antisera each prevented the effect of AVP (800 pmol) on ACTH secretion, whereas the β-ENDir response to AVP was only inhibited by about 60% by the antisera. An extract of the posterior pituitary gland administered in a dose corresponding to 0.15 or 0.5 pituitary equivalents had no effect on ACTH secretion, while 1.0 pituitary equivalent increased the ACTH concentration in plasma. This effect was abolished by AVP antiserum. The posterior pituitary extract caused a dose-dependent rise in plasma β-ENDir which might be due to an unavoidable contamination of the posterior pituitary, extract by a small amount of β-END from the intermediate lobe. Consistent with this view, AVP antiserum had no effect on the rise in the plasma concentration of β-ENDir following administration of the posterior pituitary extract. We conclude that CRH as well as AVP neurons are involved in the mediation of the HA- and stress-induced release of the POMC-derived peptide

ISSN:0028-3835    

DOI:10.1159/000126258

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Fine, varicose oxytocin-containing nerve fibers have been demonstrated in the hypothalamic arcuate nucleus in rats. Using Phaseolus vulgaris leukoagglutinin as an anterograde tracer, fine neuronal fibers of paraventricular nucleus origin could be seen throughout the arcuate nucleus. Using double immunostaining, oxytocin-immunoreactive varicose fibers were observed around or in the close vicinity of β-endorphin-immunoreactive neurons. Silver-gold-labeled oxytocin-immunoreactive presynaptic boutons were shown to make synaptic contacts with diaminobenzidine-labeled β-endorphin-immunoreactive neurons by electron microscopy. These findings provide morphological evidence for a possible influence of oxytocin on the activity of the brain β-endorphin system at the hypothalamic lev

ISSN:0028-3835    

DOI:10.1159/000126259

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Deficiency in the secretion of luteinizing hormone-releasing hormone (LHRH) from the median eminence (ME) is one of the factors limiting reinitiation of estrous cycles following parturition in cows. In previous studies, administration of naloxone, an opioid receptor antagonist, to postpartum cows increased LH secretion, suggesting that endogenous opioids inhibit the secretion of LHRH. This study employs quantitative light microscopy to describe morphological changes in the distribution of immunoreactive β-endorphin (ir-β-END) neurons in the hypothalamus of anestrous early postpartum (EPP, days 10-16, n = 5), midpostpartum (MPP, days 33-43, n = 4) and multiparous cycling cows (CYC, months 12-14, n = 4). Cryostat sections (60 µm) of perfusion-fixed ventral diencephalon and forebrain were immunostained with anti-β-END serum via the biotin-avidin-peroxidase method or double stained sequentially with anti-LHRH serum, then anti-β-END serum. In all cows, β-END immunoreactive perikarya, mostly bipolar neurons, were located in the arcuate and periarcuate nucleus (ARC), with some perikarya in the ME. Within the ARC, the percentage area immunostained for ir-β-END was greater (p < 0.01) for the CYC than EPP cows, with MPP intermediate but not significantly different from the other groups. Consistent for all cows, the percentage area of ir-β-END in ventral ARC regions was greater (p < 0.05) than dorsal ARC regions. Fibers from these neurons coursed into the anterior hypothalamus, preoptic area and bed nucleus of stria terminalis. Ventrally projecting fibers entered the ME forming a densely staining band within the external layer. The percentage area stained was similar among all three postpartum groups. Few (1%) close associations between ir-β-END varicosities and LHRH perikarya and dendrites were found in the anterior hypothalamus and ventral preoptic regions. However, within the external lamina of the ME extensive intermingling of ir-β-END and LHRH varicosities were commonly observed. The reduced area of staining in the ARC of EPP cows compared to CYC cows may reflect an altered activity of β-END neurons during t

ISSN:0028-3835    

DOI:10.1159/000126260

出版商:S. Karger AG    

年代:1992

数据来源: Karger