摘要:

We previously demonstrated that norepinephrine (NE) induction of cAMP accumulation in slices of the preoptic area (POA) and middle hypothalamus (MH) is reduced by in vivo administration of progesterone to estradiol-primed rats, apparently by eliminating α1-receptor augmentation of β-receptor-stimulated cAMP formation. The present studies examined whether in vitro exposure to progesterone would also depress NE-stimulated cAMP synthesis. POA and MH slices from estradiol-primed females were incubated with 20 nM progesterone for 5-30 min prior to addition of 100 µM NE. Pre-incubation of slices with progesterone for as little as 5 min significantly suppressed NE-stimulated cAMP formation by greater than 60%. This effect was estrogen-dependent in that progesterone in vitro did not inhibit NE-stimulated cAMP accumulation in slices from ovariectomized rats not pretreated with estradiol. Isoproterenol, a β-adrenergic agonist, elevated cAMP to the same extent in slices from estradiol-primed females incubated with and without progesterone in vitro; however, the α1-agonist, phenylephrine, was unable to augment cAMP formation in slices incubated in vitro with progesterone for 5 min prior to drug challenge. To determine whether the rapid effects of progesterone may be exerted at the level of the plasma membrane, we employed progesterone conjugated to bovine serum albumin at carbon 3 (P-3-BSA). Slices from estradiol-primed rats incubated with P-3-BSA for 5 min did not exhibit an α1-receptor augmentation of β-receptor-stimulated cAMP accumulation. These data indicate that progesterone may have rapid, non-genomic effects on α1-adrenergic receptor coupling to second-messenger systems in the hypothalamus of fema

ISSN:0028-3835    

DOI:10.1159/000126089

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effects of cocaine on rat plasma and brain α-melanocyte-stimulating hormone (α-MSH) levels have been studied by means of a specific radioimmunoassay. The selected brain areas were the hypothalamus, septum-nucleus ac-cumbens and hippocampus. Cocaine given subcutaneously decreased the α-MSH levels in the peripheral blood. Pimozide, a dopaminergic antagonist, had an opposite effect: it increased the α-MSH levels in the peripheral blood. Combined treatment with cocaine + pimozide resulted in a decrease in the pimozide-induced increase in α-MSH levels in the blood. Cocaine and pimozide or the combination of cocaine + pimozide were ineffective on the α-MSH levels in the hypothalamus and septum-accumbens brain regions. In the hippocampus, cocaine in the dose applied induced a slight but not significant decrease in the α-MSH level. Pimozide caused a significant decrease in the hippocampal α-MSH level which disappeared at 60 min. Cocaine prevented the pimozide-induced depletion of α-MSH. The data indicate that cocaine may act as a dopaminergic agonist in the mechanism of control of α-MSH secretion from the intermediate lobe of the pituitary. The α-MSH levels in the brain are controlled by different mechanisms. In some brain areas, the dopaminergic system has no action; in others the mechanisms might be similar to but slightly different from that in the

ISSN:0028-3835    

DOI:10.1159/000126090

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The thymosins are a family of hormone-like products of epithelial cells of the thymus which are important in maintenance and function of the immune system. Thymosin fraction 5, a partially purified extract of calf thymus, can influence pituitary hormone release. We have studied the effects of thymosin α1 (Tα1), the first peptide isolated from thymosin fraction 5, on thyrotropin (TSH), adrenocorticotropin (ACTH), prolactin (Prl) and growth hormone (GH) release. To evaluate its effect in vivo we injected the peptide into the third ventricle of conscious male rats and measured the concentration of the pituitary hormones in plasma at different times after the injection. Following third-ventricular injection of Tα1, there was a significant decrease in plasma TSH and ACTH concentrations in comparison with values of control groups injected with diluent. The decrease in plasma TSH was of longer duration and was obtained with a lower dose of Tα1 than that of ACTH. Also, a significant decrease in plasma Prl was observed, with the same dose as for TSH. On the other hand, there were no significant changes in plasma GH. To examine if there is any direct effect of Tα1 at the pituitary level, we incubated hemipituitaries from male rats in vitro with different concentrations of the peptide. In this system Tα1 evoked a dose-dependent release of TSH and ACTH, while there was no effect on the release of Prl and GH. There was a stimulation of luteinizing hormone (LH) but not follicle-stimulating hormone (FSH) release with a minimal effective dose of 10–12M and a dose-related increase in release to a maximal 7-fold increase in LH at the highest dose (10–7M) evaluated. The results indicate a hypothalamic effect of Tα1 to decrease the release of TSH, ACTH and Prl. On the other hand, acting directly at the pituitary level the peptide stimulates the release of TSH as well as ACTH and selectively stimulates the release of LH but not FSH. Both hypothalamic and pituitary sites of action may be of importance for the interaction between the central nervous, endocrine and immu

ISSN:0028-3835    

DOI:10.1159/000126091

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effect of perinatal hypothyroidism on hippocampal mossy fiber zinc density was examined in rats. Timed pregnant Sprague-Dawley rat dams were given water containing either 0.02% propylthiouracil (PTU) or vehicle from gestational day 18 until their litters were weaned on postnatal day 31. Hippocampal mossy fiber zinc density was reduced by 75% in both the dorsal and ventral hippocampal formation CA3 stratum lucidum region of 31-day-old PTU-treated rats compared to untreated controls. Perinatal hypothyroidism did not alter hippocampal tissue zinc concentration, indicating that the PTU-induced reduction in mossy fiber zinc was not a consequence of reduced hippocampal zinc concentration. At 120 days of age, 3 months after discontinuation of PTU treatment, hippocampal mossy fiber zinc density remained significantly reduced by 33-45% in PTU-treated rats compared to control. These data indicate that perinatal hypothyroidism causes a long-lasting reduction in hippocampal mossy fiber zinc density.

ISSN:0028-3835    

DOI:10.1159/000126092

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The relationship between GABA dynamics and LH release was studied on day 2 after subcutaneus estrogen implant in short-term ovariectomized rats. GABA accumulation, used as an index of GABA turnover, was determined in the medial preoptic nucleus (MPN), medial (MS) and lateral (LS) septal nuclei, median eminence-mediobasal hypothalamus (MBH) and locus ceruleus (LC). Measurements of GABA were performed at two different times of day (11.00 and 15.00 h), 3 h after intraperitoneal administration of γ-vinyl-GABA (GVG), an irreversible inhibitor of GABA transaminase. Either morning or afternoon ovariectomized rats (OVX) showed a significant increase in GABA accumulation after GVG treatment in all the areas studied. Estrogen-treated OVX rats showed in the morning a lower GABA accumulation in the MPN, MBH and LC, and GABA levels remained unchanged in the LS and MS. In the afternoon, the MPN and LS showed a lower rate of GABA accumulation whereas in the MBH and LC the GABA increase was not observed. In contrast the MS showed a rate of GABA accumulation similar as in the OVX rats. Local administration in the MPN of 20 µg GVG, or GAB A-A receptor stimulation by muscimol (50 ng), prior to the increase in plasma LH levels, prevented the occurrence of the estradiol-induced LH surge. The effect of muscimol was reversed by bicuculline (30 ng), a GABA-A receptor antagonist. Bicuculline in low doses lacked effect by itself. In conclusion, these results strongly suggest that a decreased GABAergic activity in MPN, MBH and LC precedes the estradiol-evoked LH surges in ovariectomized rats. Moreover, that in septal nuclei, a low GABAergic activity takes place well before the occurence of plasma LH increase. Results have shown, in addition, that the LH surges may be blocked by either increasing the GABAergic activity or stimulating in the MPN the GABA-A receptor subtyp

ISSN:0028-3835    

DOI:10.1159/000126093

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Quantitative receptor autoradiography was used to study the neuroanatomical distribution and effects of gonadal hormones on [3H] flunitrazepam binding in the male Japanese quail brain. In gonadally intact quail brains, [3H] flunitrazepam displayed a heterogeneous distribution, with elevated levels in the posterior brain regions such as the stratum griseum et fibrosum superficiale and stratum griseum centrale of the optic tectum. Lower values were observed in the anteriorly located brain sites such as the nucleus septalis (lateralis et medialis), the cortex dorsolateralis and the nucleus lateralis hypothalami. Castration affected [3H] flunitrazepam binding levels in brain areas known to contain gonadal steroid receptors as well as in some areas which were devoid of gonadal steroid receptors. Castration in fact, elevated [3H] flunitrazepam binding in the nucleus preopticus anterior and reduced binding levels in archistriatum dorsalis et ventralis and in the nucleus intercollicularis; all of these areas are known to have gonadal steroid receptors. In two regions which do not contain such receptors, namely the hyperstriatum ventrale and the cerebellum pars granularis, castration increased [3H] flunitrazepam binding. In order to determine whether the gonadal steroid effect is due to changes either in the number of binding sites (Bmax) and or affinity binding state (KD), saturation binding studies were carried out in some of the areas described above in brains of quail which were castrated or castrated and given replacement therapy with testosterone or estradiol for 2 weeks. In keeping with the suppressive effect of the gonads inferred from the castration results described above, testosterone and estradiol decreased the Bmax of [3H] flunitrazepam binding in the hypothalamus preoptic area, while in hyperstriatum ventrale only estradiol produced a significant decrease of the Bmax. We then tested for the effects of GAB A on [3H] flunitrazepam binding to the receptors and found that GABA intensified the depressive activity of gonadal steroid replacement therapy in the hyperstriatum ventrale and in the hypothalamus-preoptic area as shown respectively by the approximate 45 and 40% greater decrease of Bmax. However when the GABA effect on [3H] flunitrazepam binding in the presence of GABA was expressed as ratio, only the hyperstriatum ventrale revealed a significantly enhanced potentiation effect following castration, while a significant suppression of this potentiation effect was obtained by both T and E replacement therapy. These results suggest that a GABA-benzodiazepine receptor interaction might be involved in the regulation of some hormone-mediated cerebral functions in the male quail such as neuroendocrine and sociosexual behavior.

ISSN:0028-3835    

DOI:10.1159/000126094

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

We previously reported that the injection of neostigmine, an acetylcholine esterase inhibitor, into the dorsal hippocampus produced hepatic venous plasma hyperglycemia associated with an increase of epinephrine and glucagon in anesthetized fed rats. To evaluate the relative contribution of these glucoregulatory hormones and the nervous system to the net hyperglycemic response, we unilaterally injected neostigmine (5 × 10–8 mol) into the dorsal hippocampus in the following groups of rats: intact rats with bilateral adrenalectomy to eliminate the action of epinephrine, and rats receiving a constant infusion of somatostatin and insulin to prevent the glucagon response and to maintain the basal insulin level. Hepatic venous plasma levels of glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine were determined. The area under the glucose curve during the 120-min period following the injection of neostigmine was compared between groups. The areas under the glucose curve for rats receiving somatostatin and insulin, adrenalectomy rats, and adrenalectomy rats receiving somatostatin and insulin were, respectively, 82, 31, and 61% of that for intact rats. The fashion of hippocampal stimulated hyperglycemia with neostigmine was similar to that after injection of neostigmine into the third cerebral ventricle. Therefore, we investigated hyperglycemia in rats with lesions of ventromedial hypothalamus and found that the response to hippocampal neostigmine was significantly inhibited by the hypothalamic lesion. These findings suggest that the glucoregulatory hippocampal activity evoked by neostigmine may be transmitted to peripheral organs via the ventromedial hypothalam

ISSN:0028-3835    

DOI:10.1159/000126095

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The density of µ-opiate receptors located in the medial preoptic area (MPOA) of the rat hypothalamus is cyclical and sexually dimorphic. The hormonal regulation of MPOA µ-receptors was examined in ovariectomized rats treated with a variety of hormone regimens. In experiment 1, animals received acute estradiol (E2), progesterone (P), or prolactin (PRL), or E2 followed in 48 h by either P or vehicle by subcutaneous injection. Brains were removed 3 h after the final injection. In experiment 2, animals were implanted with empty or E2-filled Silastic capsules, and received either P or vehicle by injection 48 h later, at which time E2 capsules were removed. One group received E2 implants which remained in place following sham removal surgery. Brains and trunk blood for radioimmunoassay of E2 and P were collected 3, 27 or 51 h after the final injection. Frozen brain sections were prepared, incubated in [3H]D-Ala2, MePhe4, Gly-ol5-enkephalin, which selectively labels µ-receptors, and analyzed using quantitative receptor autoradiography. P treatment significantly increased MPOA µ-receptors, but only 27 h after E2 priming. Neither shorter P exposure, nor E2, P or PRL alone affected MPOA µ-recepter density. Following this delayed E2, P-induced increase, µ-receptor density subsequently decreased in the presence or absence of E2. The results suggest that E2, P treatment produces a gradual and transient increase of MPOA µ-receptor density. The subsequent decrease of receptor density is independent of the presence of E2 and may be related to receptor turnover. The time course of this effect is consistent with that of the estrus cycle. Such hormone-induced regulation of MPOA µ-receptor density could influence the physiologic effects of opiates on gonadotropin secretion and reproductive behavior in cycling

ISSN:0028-3835    

DOI:10.1159/000126096

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The effects of thyroid hormones (TH) on brain immunoreactive-vasoactive intestinal peptide (IR-VIP) secretion and content in cultured fetal rat cortical cells were studied. Cerebral cortical cells were maintained as monolayer cultures for 14-18 days. T3 or T4 (10–7M) caused a time-dependent decrease in total IR-VIP. Significant suppression was observed following treatment periods of 6 h or longer (24 and 48 h). Depending on the length of time cells had been deprived of TH prior to the addition of exogenous T3 or T4, these two thyroid hormones had different effects on IR-VIP accumulation. Both T3 and T4 caused a dose-dependent suppression or IR-VIP accumulation when there was no deprivation period or when it lasted 4 h. However, a biphasic effect was observed when cells were deprived of TH for 17 and 24 h: low doses of T3 or T4 (from 10–12 to 10–10M) significantly increased (p < 0.05) total IR-VIP, while high T3 or T4 doses (10–8 and 10–7M) caused a significant decrease (p < 0.01). The TH action was furthermore shown to be reversible. After T3 (10–7M) removal and subsequent incubation in serum-free medium for 6, 24 and 48 h, T3-treated and control cells exhibited similar levels of IR-VIP release and content. At this time, a new exposure to T3 (10–7M) again had a suppressive effect. These findings suggest that at this time of brain development, VIP release and content in cerebral cortical cells is affected by TH in a time- and dose-related manner, and furthermore this seems to

ISSN:0028-3835    

DOI:10.1159/000126097

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Delta-sleep-inducing peptide (DSIP) colocalizes within gonadotropin-releasing-hormone (GnRH)-containing neurons in adult hypothalamus and could play a role in the regulation of hypothalamic-pituitary axis in adults. To support the possibility that DSIP also participates in fetal neuroendocrine events and to demonstrate the ontogenic evidence of coexisting neuropeptides, we have performed a detailed immunocytochemical study of DSIP- and GnRH-immunoreactivity in fetal hypothalamus of guinea pig. Using indirect immunofluorescent and sequential double-immunolabeling (elution-restaining) techniques, the results indicated that DSIP immunoreactivity was initially detected at the 38th day of gestation. In contrast to the first appearence of GnRH immunoreactivity at day 28, therefore, a 10-day delay was found. Such a delay remains as yet unexplained. From its first occurrence, DSIP immunoreactivity was always labeled with GnRH, whereas some of GnRH-immunoreactive structures did not display a DSIP immunoreactivity. But with the growth of fetus, especially before and after birth, a complete overlap between DSIP and GnRH immunoreactivity was observed throughout various regions of hypothalamus. Attention was also focused on prenatal morphological development of DSIP/GnRH- and GnRH-immunolabeled neurons. Initially, labeled neurons were visualized as uni- or bipolar types. Thereafter, their smooth and irregular subtypes could be distinguished. During later fetal age, relatively mature features were evident such as the increase of multipolar and irregularly labeled neurons. Taken together, these data provide, for the first time, anatomical evidence that DSIP exists in fetal hypothalamus and that, like GnRH, it could regulate the hypothalamic-pituitary axis during ontogenesis.

ISSN:0028-3835    

DOI:10.1159/000126098

出版商:S. Karger AG    

年代:1992

数据来源: Karger