ISSN:0028-3835    

DOI:10.1159/000127090

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Pituitary adenylate cyclase-activating polypeptide (PACAP) receptors were characterized and their function investigated in mouse pituitary neurointermediate lobe explants. We show that mouse neurointermediate lobes can be maintained for up to 1 month in defined medium. After 8 days in culture, these explants are devoid of any of the original tyrosine hydroxylase or glutamate decarboxylase immunoreactive fibers, which in situ innervate the melanotropes. Under these culture conditions, no mitotic activity is detectable in melanotropes and these cells remain sensitive to physiological regulation such as dopamine and corticotropin-releasing hormone. Using in situ hybridization and polymerase chain reaction, we show that in situ and in neurointermediate lobe explants, melanotropes express PACAP receptor type I isoforms that transduce through the cAMP and inositol phosphate pathways. In neurointermediate lobe explants, PACAP 27 and PACAP 38 (10–8M) stimulate cAMP accumulation whereas PACAP 38 but not PACAP 27 stimulates inositol phosphate breakdown. However, both ligands are potent stimulators of proopiomelanocortin (POMC)-derived peptides exocy-tosis and POMC gene transcription. In addition, stimulation of POMC gene transcription is mediated both by cAMP and by inositol phosphate pathways. Taken together, our data suggest that PACAP is a major regulator of melanotrope function

ISSN:0028-3835    

DOI:10.1159/000127091

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Daytime restriction of food availability phase-shifts the diurnal periodicity of plasma corticosterone (B) concentration in rats. However, the changes at the various functional levels in the hypothalamic-pituitary-adrenal (HPA) axis are not completely understood. We performed studies in two groups of Wistar rats, a control group with free access to food and a food-restricted group with access to food only from 09.00 to 11.00 h for 14 days. The basal plasma B and ACTH concentrations in the control group presented diurnal variation with higher values in the afternoon than in the morning. In the food-restricted group there was a 12-hour shift of peak B values. Plasma ACTH levels were high in the morning, but there was no significant difference between morning and afternoon values. Plasma AVP presented no diurnal variation in the control group. In the food-restricted group, the diurnal variations of plasma AVP and ACTH-B did not coincide. There was no detectable nycthemeral variation of pituitary ACTH or hypothalamic CRH and AVP contents in either group. Plasma ACTH did not exhibit any diurnal variation in response to CRH in free-fed or food-restricted rats anesthetized with chlorpromazine-morphine-pentobarbital. The administration of ACTH (1-24) resulted in higher B levels in the afternoon in control rats pretreated with dexamethasone once or twice. In the food-restricted group there was a 12-hour shift in the adrenal response to ACTH (1-24). These patterns of response were abolished in both groups when the rats were anesthetized. An in vitro study showed no diurnal variation in adrenal responsiveness to 10-6M-10-9M ACTH (1-24) stimuli. Our results suggest that anesthesia-related neural or humoral factor(s) other than ACTH are involved in the diurnal periodicity of the HPA axis in free-fed rats and in its shifts in food-restricted rats.

ISSN:0028-3835    

DOI:10.1159/000127092

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Galanin is a 29 amino acid neuropeptide widely distributed throughout the mammalian nervous and endocrine system. We have previously reported that estrogen dramatically increases galanin gene expression and protein synthesis in the anterior pituitary (AP), while the expression in the uterus (UT) of the same animals is transient and similar to the induction of protooncogenes (c-fos, c-jun, c-myc). In order to examine if this pattern of induction is specific to estrogen administration, we investigated the effect of glucocorticoids, another steroid, on the gene expression of galanin in the AP and in the UT of ovariectomized female rats and in the AP of male rats. Using Northern blot analysis, the AP and the UT showed almost undetectable levels of galanin mRNA, but in vivo treatment of female rats with 1 mg/kg body weight of dexamethasone (DEX) led to a significant increase of galanin mRNA levels in both AP and UT. Similarly, DEX (0.1-5 mg/kg i.p.) significantly stimulated galanin mRNA levels in the AP of the male rats. In both males and females the peak of induction was at 9 h after injection that is different from the 3-hour peak after estrogen administration. Daily injection of DEX for up to 7 days sustained the levels of galanin mRNA in both the AP and the UT, in contrast to the transient induction of galanin in the UT after estrogen administration. No change was noted in the galanin protein content of AP (control = 30 ± 3.5 ng/mg protein; DEX treated = 38 ± 4.2 ng/mg protein). Interestingly, in the UT of ovariectomized rats the combination of DEX and DES (diethylstilbestrol) treatment for 2 days resulted in a synergistic stimulation of galanin mRNA. In summary, these data demonstrate a tissue- and steroid-specific regulation of the galanin gene in AP and UT and suggest that DEX regulates the galanin gene possibly through a pathway different from estroge

ISSN:0028-3835    

DOI:10.1159/000127093

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Brief periods of hypoxia during labour and birth are a frequent occurrence. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia in both adult and immature animals. The hippocampus also contains the highest concentration of corticosteroid receptors of any brain region and both mineralocorticoid (type I) receptors and glucocorticoid (type II) receptors in the hippocampus play a role in the regulation of basal diurnal and stress-induced glucocorticoid secretion. Given this background, the aim of this study was to test whether an acute period of anoxia during the birth process may have lasting effects on CNS corticosteroid receptor levels and/or pituitary-adrenocortical function. Type I and type II corticosteroid receptor binding sites in the hippocampus and hypothalamus were compared in adult rats that had been born vaginally, born by a Caesarean procedure or born by a Caesarean procedure with 5,10 or 15 min of added anoxia. Using 14 nM [3H]corticosterone as radioligand, mineralocorticoid receptor binding was reduced by approximately 50% in the hippocampus and hypothalamus of adult rats that had been born by the Caesarean procedure either with or without an added period of anoxia, in comparison to vaginally born controls. Saturation analysis revealed that these reductions resulted from decreases in affinity of the mineralocorticoid receptor for [3H]corticosterone, with no change in numbers of receptors. Birth condition had no effect on glucocorticoid receptor binding capacities in the hippocampus or hypothalamus. A small increase in basal corticosterone secretion during the diurnal trough was observed in adult animals that had been born by Caesarean section with 5 or 15 min of added anoxia. The plasma corticosterone response to a 20-min restraint stress was reduced in adult animals born by Caesarean section with or without an added period of anoxia, in comparison to vagmally born controls. However the adrenocorticotropin response to stress was largely unaffected by birth condition. The results indicate that an acute birth insult is sufficient to produce long-lasting alterations in hippocampal and hypothalamic mineralocorticoid receptor sites, accompanied by changes in basal and stress-induced glucocorticoid secretion.

ISSN:0028-3835    

DOI:10.1159/000127094

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effect of acute corticosterone (CORT) treatment on elaboration of long-term potentiation (LTP) and short-term potentiation (STP) in intact and adrenalectomized rats was investigated. Both forms of synaptic plasticity were evaluated as fractional increases in population spike amplitude in dentate gyrus granule cells following brief, high-frequency stimulation of the medial perforant pathway in vivo. LTP was distinguished from STP by the magnitude and time course of population spike facilitation. Adrenalectomy resulted in profound reduction of LTP extent, without any significant effect upon STP. Replacement of glucocorticoid by a single injection of CORT to previously adrenalectomized rats restored LTP to control levels. When CORT was applied to intact subjects, it slightly, but significantly, impaired LTP development. No effect of CORT on STP induction and time course was found. Taken together, these results show that the modulation of synaptic efficiency in hippocampal dentate gyrus by circulating glucocorticoid depends on the form of plasticity examined. LTP was found to be more susceptible to the impairment induced by both high and low levels of glucocorticoid than STP.

ISSN:0028-3835    

DOI:10.1159/000127095

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Biological activity of the follicle-stimulating hormone (FSH) is dependent on its pattern of glycosylation and is altered during galactosemia, a genetic disease characterized by deficient activity of galactose-1-phosphate uridyltransferase (GALT). To assess the role of this enzyme in the synthesis of FSH, the expression of GALT at the mRNA and protein levels was measured in the whole anterior pituitary during the estrous cycle of rat. GALT was maximally expressed during the proestrous and estrous phases of the estrous cycle. The expression pattern of GALT was associated with gonadotropin-expressing cells. This close association is in accordance with the postulated role of GALT in modulating biological activity of FSH.

ISSN:0028-3835    

DOI:10.1159/000127096

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Insulin-induced hypoglycemia (ΠH) has been reported to inhibit luteinizing hormone (LH) secretion in ovariectomized ewes as well as in intact or gonadectomized female rhesus monkeys. An infusion of naloxone, a specific opiate receptor antagonist, while able to prevent this inhibitory effect in ewes, was ineffective in monkeys, suggesting a difference in the mechanisms involved in the response to IIH in these two species. The present study was designed to investigate the influence of this stimulus on the dynamics of LH release and the possible activation of an opioidergic pathway in the long-term castrated male rat. Blood samples were collected every 7 min, for several hours, in freely-moving rats bearing a jugular cannula. The intravenous injection of 0.4 IU of insulin triggered an acute hypoglycemia and reduced LH release. In contrast, during a continuous intravenous naloxone infusion (0.5 mg/kg/h), insulin, while still lowering the glycemia, failed to affect the LH secretory pattern. In a control experiment, naloxone infusion alone had no significant effect on mean LH concentration and pulse intervals. These experiments indicate that, in long-term gonadectomized male rats, IIH impairs the LH secretory pattern, and that endogenous opioid peptides are involved in this response

ISSN:0028-3835    

DOI:10.1159/000127097

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The possible role of the conceptus in stimulating the onset of maternal behavior through its secretion of placental lactogens and their passage into the brain was investigated in female rats. In the first study, significant mitogenic activity in the Nb285%), but not by antibodies to rPL-I, indicating that the predominant lactogen in the CSF prepartum is rPL-II. The behavioral actions of placental secretions were assessed in the third experiment by infusing recombinant rPL-I and purified rPL-II directly into the medial preoptic area of the brain of steroid-primed, nulliparous rats. Latencies to respond maternally to foster young were significantly reduced in rPL-I- and rPL-II-treated rats (2- to 3-day latencies) when compared with latencies in control females (5- to 6-day latencies). Thus, the conceptus through its secretion of rPLs which apparently gain access to the CSF helps to prime the pregnant female’s brain to respond maternally at the end of gestation. This endocrine communication between the developing conceptus and pregnant female appears to be an important part of the biological system which helps to establish successful maternal c

ISSN:0028-3835    

DOI:10.1159/000127098

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Hypothyroidism is associated with both reduced central 5-HT function and an increased incidence of depression. This study tested the hypothesis that the reduced 5-HT function returns to normal with thyroxine replacement therapy. Seven hypothyroid patients were tested before and after adequate thyroxine replacement. Cortisol and prolactin responses to d-fenfluramine, a centrally acting 5-HT-releasing agent, were used as an index of central (hypothalamic) 5-HT responsiveness. 5-HT-mediated cortisol responses were significantly higher after thyroxine replacement. Basal prolactin levels were reduced, but 5-HT-mediated prolactin responses were not significantly higher after treatment, perhaps due to the pre-treatment responses being elevated by the direct stimulatory effects of hypothyroidism itself on pituitary prolactin secretion. Depressive symptomatology improved with thyroxine. TSH levels were positively related to depressive symptomatology, and inversely to cortisol responses. Depressive symptomatology was inversely related to cortisol responses. These findings thus provide further support that central 5-HT neurotransmission is affected by hypothyroidism. They also suggest that the reduction in 5-HT responsiveness is reversible with thyroxine replacement therapy.

ISSN:0028-3835    

DOI:10.1159/000127099

出版商:S. Karger AG    

年代:1996

数据来源: Karger