摘要:

Roman high- (RHA) and low- (RLA) avoidance rats are selected and bred for rapid versus non-acquisition of two-way, active avoidance behavior in a shuttle box. They also show a number of other behavioral differences which appear to be essentially related to emotional factors, the RLA rats being emotionally more sensitive. The ACTH secretory response to stressors is also augmented in RLA rats. We thus raised the question whether the expression of corticotropin-releasing factor (CRF) and vasopressin (VP), two neurohormones exerting a synergistic action on ACTH release from corticotropic cells, is different in the two strains. Steady-state mRNA levels were examined in the parvicellular neurons of the paraventricular nucleus under basal conditions and 4 h after a single 8-min exposure to an open-field stressor. In situ hybridization histo-chemistry with 35S-labeled oligonucleotide probes was followed by quantitative cell by cell autoradiography. When basal CRF and VP mRNA levels were compared in the two lines, we found that the RLA rats had a significantly higher VP-labeling density than the RHA rats. No difference was found for CRF mRNA. During open-field exposure, we observed behavioral differences paralleled by elevated corticosterone compatible with an increased emotional response in RLA rats. Open-field exposure produced a significant increase in CRF but not VP mRNA in both RHA and RLA rats (by 43 and 57%, respectively). These results suggest that differences in basal VP expression in CRF neurons may participate in the mechanisms underlying the hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis in the emotionally more sensitive RLA rats. Thus, these Swiss sublines of RHA-RLA rats might provide a useful model to study the role of genetic predisposition and superimposed environmental factors on the regulation or dysregulation of the HPA axis.

ISSN:0028-3835    

DOI:10.1159/000126829

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Copulatory behavior was studied in five groups of sexually experienced, gonadally intact male rats in which: (i) the nonsteroidal aromatase inhibitor Fadrozole (CIBA-Geigy CGS 16949A) was delivered bilaterally (0.756 µg in 6.0 µl saline in 24 h to each side) into the medial preoptic area (POM) together with normal saline given s.c. via osmostic minipumps (n = 10); (ii) normal saline was delivered bilaterally into POM together with the same dose of Fadrozole s.c. (n = 9); (iii) Fadrozole was delivered bilaterally into the lateral preoptic area together with normal saline given s.c. (n = 6); (iv) Fadrozole was delivered bilaterally into the cerebral cortex together with normal saline given s.c. (n = 6), and (v) unoperated controls (n = 14). Mounting and ejaculation were significantly decreased in rats receiving Fadrozole in POM compared with the behavior of rats in the other 4 groups. Few differences occurred between rats in the latter 4 groups, all of which continued to mate. The H222 and ER-715 anti-estrogen receptor (ER) antibodies were used to examine the distribution of ER immunoreactive (ERir) neurons in hypothalamic and limbic sites in gonadectomized controls and in some of the rats in groups i, ii and v. Since labeling of ERir neurons in rat brain with the H222 anti-ER antibody is reported to be inhibited by estrogen, it was used here to identify regions (with staining) where the aromatization of testosterone (T) into estradiol (E2) had been suppressed. Intense H222 ERir nuclear neuronal labeling was confined to the POM of males receiving Fadrozole in POM, and significantly more labeled neurons were found in the POM of these rats than in the POM of rats treated with saline in POM. In contrast, the ER-715 antibody, which is reported to stain neurons independently of hormonal status, labeled neuronal nuclei in hypothalamic and limbic regions of all groups, demonstrating the presence of ER. These findings show that conversion of T into E2 in the POM of the male rat is important for male rat copulatory behavior and that H222 ERir nuclear neuronal labeling can be used to identify the neurons in POM that were affected by Fadrozol

ISSN:0028-3835    

DOI:10.1159/000126830

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Somatostatin (ST) inhibits gastrointestinal motility and exocrine and endocrine secretions. In animals, ST has been demonstated to decrease food intake. We investigated, in a randomized double-blind investigation in 10 healthy humans, the effects of an intravenous ST infusion compared to saline on subjective hunger feelings. After 1 h, a low dose of fat was given intraduodenally to induce the release of endogenous upper-intestinal satiety factors. Ninety minutes later sandwiches were served and eaten until satiation. In the first hour, when no intraduodenal fat was given, there was a significant decrease in feelings of hunger with ST (p < 0.05). During the intraduodenal fat infusion this pattern reversed with a trend towards less satiety with ST. Food intake during intraduodenal fat infusion tended to be higher during ST (305 ± 42 g) than during saline (205 ± 36 g) although not significantly. In the 5 h after the experiment hunger feelings were significantly less after ST. In conclusion, we found evidence for a satiety effect of ST in humans which reversed towards less satiety when intraduodenal intralipid, which presumably produced endogenous satiety factors, was given. Postmeal satiety is higher after S

ISSN:0028-3835    

DOI:10.1159/000126831

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We have studied the role of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) on salt appetite developed by deoxycorticosterone acetate (DOCA) treated rats. To this end, we measured the effects of DOCA given on alternate days on salt intake; MR and GR in hippocampus (HIPPO), amygdala (AMYG), and hypothalamus (HT); (3) the activity of ornithine decarboxylase (ODC), a GR-mediated response, and (4) the salt intake after treatment with the antiglucocorticoid RU 486 or the antimineralocorticoid ZK 91587. First, we demonstrated that 10 but not 1 mg DOCA induced natrio-genesis. Forty-eight hours after adrenalectomy and 24 h after the last DOCA injection, 10 but not 1 mg hormone reduced binding to GR in HIPPO, AMYG, and HT. Both doses of DOCA also reduced the binding to MR in HIPPO, without changes in AMYG; in HT the 1-mg dose was without effect, but the natriogenic dose (10 mg) highly increased binding of [3H]-corticosterone to MR. Scatchard analysis demonstrated increased Bmax and Kd values in the HT of DOCA-treated rats. Occupation of GR by DOCA did not stimulate the ODC activity, in contrast to the four-fold increment effected by the glucocorticoid dexamethasone. Also, administration of RU 486 did not inhibit the salt intake promoted by DOCA, in contrast to ZK 91587 which partly delayed the natriogenic effect of DOCA. It is suggested that brain MR are involved in the natriogenic effect of DOCA, whereas the role of GR is inconclusive. Although GR were occupied by DOCA, this compound did not show agonistic properties regarding induction of ODC nor antagonism of dexamethasone-induced ODC, indicating that DOCA (or its metabolites) rendered inactive GR.

ISSN:0028-3835    

DOI:10.1159/000126832

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Although binding sites for prolactin (PRL) have been mapped and partially characterized in the brains of several species, there is as yet no direct evidence that the effects of intracranial PRL on brain function are receptor-mediated events. We addressed this question by testing whether antibodies generated against rat liver PRL receptors can effectively antagonize the ability of PRL to enhance feeding behavior in male ring doves (Streptopelia risoria). Both agents were administered directly to the ventromedial hypothalamic nucleus (VMN), which is an effective site of PRL action in promoting hyperphagia in this species. In the initial study, affinity-purified γ-globulin (IgG) from the receptor antiserum preparation was tested for its ability to compete with 125I-ovine PRL for binding to receptors in rat liver, dove choroid plexus, and 6 PRL-sensitive dove brain regions using in vitro quantitative film autoradiogra-phy. Although the binding affinity of the anti-PRL receptor antibodies was at least 50 times lower in dove brain than in rat liver, a 40-50% inhibition of specifically bound 125I-ovine PRL was observed in choroid plexus and in 5 of 6 brain regions with anti-receptor IgG concentrations of 5.8 × 10-7M and 1.2 × 10-6M, using sections incubated with normal rabbit serum (NRS) IgG as a control. In a second study, anti-PRL receptor IgG or NRS IgG (2.4 µg) was injected unilaterally into the VMN at 45-60 min prior to VMN injection of ovine PRL (50 ng) or saline vehicle. This procedure was repeated at twice-daily intervals for 5 days. When compared to the feeding behavior of PRL-injected birds given NRS IgG, anti-receptor antibody-treated animals showed a marked reduction in PRL-induced hyperphagia. The magnitude of this reduction was calculated to be approximately 50% after corrections were made for a mild hypophagia induced by the anti-receptor IgG treatment alone, as reflected in the feeding behavior of the anti-PRL receptor IgG + vehicle-treated group. These results suggest that PRL receptors in dove brain and rat liver exhibit structural similarities as well as differences and that the hyperphagia induced by intracranial injections of PRL is mediated, at least in part, by interactions with PRL receptors in the br

ISSN:0028-3835    

DOI:10.1159/000126833

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Considerable evidence supports the existence of a bidirectional communication between the immune system and the hypothalamo-pituitary-adrenal (HPA) axis. In the present study, we examined the interleukin-1β (IL1β)-mediated regulation of pro-opiomelanocortin (POMC) at a cellular level, from secretion to gene expression, using murine anterior pituitary corticotroph tumor (AtT20) cells as a model system. The regulatory effects of IL1 β were compared to those of the classical POMC regulator, corticotropin-releasing hormone (CRH). IL1β was found to evoke an early, preferential release of β-lipotropin (βLPH) which was accompanied by elevations in POMC heteronuclear (hn)RNA and c-fos and c-jun mRNAs. IL1β also elicited a late, preferential release of βLPH which was associated with only an enhanced expression of POMC hnRNA. Additionally, IL1β stimulated an intermediate, preferential release of β-endorphin (βE) which was not accompanied by any changes in gene expression. In marked contrast to IL1β, CRH evoked an early, preferential βE secretory response which was associated with elevations in POMC hnRNA and c-fos mRNA. CRH also elicited a late, preferential βE release which was associated with only an enhanced POMC hnRNA expression. These findings show that although both IL1 β and CRH activate the corticotrophs, they elicit dramatically different patterns in the regulation of the biochemical dynamics of POMC. Such distinct patterns of corticotroph activation in response to IL1β or CRH exposure in vivo would allow the pituitary not only to indicate that it has been activated, but also how it has been activated. This characteristic may be critically important in the function of the HPA axis and in the interaction of the HPA axis with th

ISSN:0028-3835    

DOI:10.1159/000126834

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We studied the effect of glucocorticoid pretreatment, mediobasal hypothalamus lesion (MBHL) and the interaction between clonidine and yohimbine in male Wistar rats to elucidate the sites and/or mechanisms of endocrine actions of α2-antagonists. The pretreatment of 1 mg/kg s.c. dexamethasone for 4 days effectively prevented the stimulatory effect of α2-antagonists yohimbine (5 mg/kg i.p.) and CH-38083 (1 mg/kg i.p.) on adrenocorticotropin (ACTH) secretion, while the action of these antagonists on prolactin (PRL) and β-endorphin (βE) remained unchanged. The central (i.c.v.) pretreatment of 5 µg/ rat clonidine failed to antagonize the prolactin (PRL) and βE releasing effect of yohimbine. However, it inhibited the yohimbine-induced ACTH secretion. MBHL resulted in a significant enhancement in basal plasma PRL and β-endorphin (βE) levels. But basal plasma ACTH levels have not been changed. Yohimbine failed to stimulate ACTH secretion in MBH-lesions rats, while PRL and βE response to the yohimbine was maintained in these animals. This study confirms that the α2-antagonists stimulate ACTH secretion by a cortico-steroid-sensitive mechanism which is located centrally. In contrast, α2-antagonists affect PRL and βE secretion via a corticosteroid-insensitive mechanism located at the periphery, possible within the pitu

ISSN:0028-3835    

DOI:10.1159/000126835

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We recently obtained evidence that activation of the 5HT1A subtype receptor enhances both plasma ACTH and prolactin (PRL) concentrations in rats. In order to explore the possible neuroanatomical structures involved in this interaction, we examined ACTH and PRL responses to intracerebral infusions of the 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (80HDPAT). In addition we also tested in vitro effects of 80HDPAT added to the perifusion medium of pituitary cells or of hypothalamic slices on hormone or neurotransmitter release, respectively. The ACTH response to 80HDPAT (0.1 mg/kg) was decreased after depletion of endogenous 5HT stores by p-chlorophenylalanine (PCPA) treatment. In contrast, the PRL response was markedly increased under that condition. Infusion of 80H-DPAT (1 µg/µl/l5 min) into the dorsal raphe nucleus induced a slow elevation of ACTH release but was ineffective on PRL secretion while infusion of 80HDPAT into the PVN induced a moderate elevation of both ACTH and PRL. After bilateral destruction of the PVN, PRL response to 80HDPAT (0.1 and 0.25 mg/kg) was markedly potentiated. In contrast, PVN-lesioned animals showed a blunted ACTH response to 80HDPAT. Basal or CRF-stimulated ACTH secretion rates from perifused dispersed adenohypophyseal cells were not affected by 80HDPAT but the 5HT1A agonist induced a very slight and transient inhibition of PRL release. 80HDPAT antagonized, in a dose-dependent manner, the K+-induced release of 3H-DA previously taken up in neurons of mediobasal hypothalamic slices. This data suggests that major sites of 5HT1A interaction in PRL and ACTH regulation are located within the CNS and not in the pituitary. ACTH but not PRL control involves presynaptic interactions and autoreceptors in the raphe nuclei as suggested by the blunted response obtained after 5HT depletion by PCPA. Sites of 5HT1A interaction with PRL regulation cannot be definitely identified from our experiments but increased responsiveness to 5HT1A after PVN lesions suggests that this nucleus exerts a negative tone on PRL secretio

ISSN:0028-3835    

DOI:10.1159/000126836

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Stress stimulates secretion of the pro-opiomelanocortin (POMC)-derived peptides adrenocorticotropic hormone (ACTH), β-endorphin (β-END) and α-melanocyte-stimulating hormone (α-MSH) from the anterior lobe (AL) and intermediate lobe (IL) of the pituitary gland. The secretion of POMC-derived peptides from the AL and IL is differentially regulated and the relative contribution of the lobes may vary with the stimulus. We investigated (1) the relative importance of the AL and IL as source of POMC-derived peptides released in response to restraint and ether stress by selectively inhibiting the corticotropes of the AL by dexamethasone (DEX) or selectively inhibiting the melanotropes of the IL by bromocriptine (BR), and (2) whether β-adrenergic blockade by propranolol could be used to discriminate between the stress-induced effect on POMC secretion from the AL and IL as has previously been suggested. Selective inhibition of AL secretion by DEX totally blocked the ACTH response to restraint and ether stress, but only partially inhibited the β-END response. The α-MSH response to both stressors was not affected by DEX. Conversely, selective inhibition of IL secretion by BR totally blocked the α-MSH response to both stressors, partially inhibited the β-END response but did not influence the ACTH response. In response to restraint stress, β-END was secreted equally from the AL and IL, whereas the IL was the most important source of β-END in response to ether stress. Blockade of β-adrenergic receptors with propranolol inhibited the β-END- and α-MSH responses to restraint stress whereas the ACTH response was unaffected. The secretory response of both ACTH, β-END and α-MSH to ether stress was inhibited by propranolol. We conclude, that (1) restraint- and ether-stress-induced secretion of ACTH and α-MSH are of AL and IL origin, respectively, (2) β-END secreted in response to restraint stress originates almost equally from the AL and IL, whereas the source of β-END in response to ether stress is mainly the IL, and (3) β-adrenergic blockade by propranolol cannot be used to discriminate between the AL and IL as the source of POMC peptides secreted in

ISSN:0028-3835    

DOI:10.1159/000126837

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

From about 10 to 36 h after superior cervical ganglionectomy (SCGx), peripheral sympathetic nerve terminals in the median eminence degenerate, nerve ending content is released, and a transient period of increased postsynaptic activity ensues. After this time, an irreversible, paralytic phase is established in the denervated territory. The present experiment was undertaken to examine, at single points during the wallerian degeneration phase (24 h after SCGx) and during the paralytic phase (10 days after denervation), the participation of peripheral sympathetic nerves in restraint-stress-induced changes of circulating luteinizing hormone (LH), prolactin (PRL), growth hormone (GH) and corticosterone levels. During the wallerian degeneration phase, serum LH did not augment after stress, as it did in sham-operated controls. In the paralytic phase, the poststress increases in LH attained similar values in sham-operated and SCGx rats. Immobilization stress augmented PRL levels to a similar extent in sham-operated and SCGx rats either 24 h or 10 days after surgery. During the wallerian degeneration phase, a decrease in serum GH levels was found in unrestrained rats. Immobilization stress decreased GH levels to 5-12% of unrestrained values in sham-operated and SCGx rats at both examination time points after surgery. Rats studied 24 h after SCGx exhibited significantly augmented serum corticosterone levels and failed to show restraint-stress-induced stimulation of corticosterone release. In rats subjected to SCGx 10 days earlier, both basal and poststress levels of corticosterone did not differ from sham-operated controls. The results suggest that the activity of peripheral sympathetic nerve terminals may modulate the acute stress responses of LH and corticosterone, but not those of GH and PRL, in rats.

ISSN:0028-3835    

DOI:10.1159/000126838

出版商:S. Karger AG    

年代:1995

数据来源: Karger