摘要:

To evaluate whether dopaminergic treatment may modify endogenous opioid activity at the hypothalamic-pituitary level, the effects of naloxone infusion (1.6 mg/h for 4 h) on luteinizing hormone (LH) secretion were studied in 5 postmenopausal women either before or after chronic administration of the dopaminergic drug bromocriptine (BCT; 5 mg/day for 30 days). BCT administration did not modify mean plasma LH levels. Before treatment naloxone infusion did not induce any significant modification of LH secretion. Conversely, after chronic BCT administration naloxone induced a significant (p < 0.05) increase in plasma LH levels. The LH response to naloxone was significantly (p < 0.001) higher than that observed before BCT. The present data show that chronic BCT administration restores the LH response to naloxone in postmenopausal women. Therefore, these results seem to demonstrate that BCT administration can enhance opioid activity, suggesting an involvement of the endogenous opioid system in dopaminergic modulation of gonadotropin release.

ISSN:0028-3835    

DOI:10.1159/000124907

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Testosterone and estradiol have been shown to affect the hypothalamic content of several pro-opiomelanocortin (POMC)-derived peptides in castrated male and female rats, respectively. It was unclear, however, whether the effects of testosterone on hypothalamic POMC were due to conversion by aromatization to estradiol or whether there were independent androgen actions on hypothalamic POMC. In order to answer this question, the effect of treatment with the nonaromitizable androgen 5-α-dihydrotestosterone (DHT) on the concentration of β-endorphin (β-EP) in the medial basal hypothalamus (MBH) was studied in castrated male rats and compared to the effect of treatment with testosterone or estradiol. The concentrations of two other POMC-derived peptides, corticotropin-like intermediate lobe peptide (CLIP) and α-MSH were measured as well. Adult male rats were castrated and received either no treatment or treatment with subcutaneously implanted silastic capsules, containing either DHT, testosterone or estradiol, designed to produce steroid levels in a physiological range. After 4 weeks the mean concentration of β-EP in the MBH of the untreated castrated rats was 1,640 ± 56 fmol/mg protein. This was reduced significantly to 1,184 + 74 fmol/mg protein after DHT treatment (p < 0.001). Similar reductions to 1,340 + 95 and 1,130 ± 85 fmol/mg protein were noted after testosterone and estradiol treatment, respectively. The mean CLIP concentration of 1,870 ± 73 fmol/mg protein in the untreated animals fell to 1,390 ± 95 after DHT (p < 0.001) compared to 1,520 ± 105 and 1,260 ± 101 after testosterone and estradiol treatment, respectively. α-MSH was similarly reduced from 911 ± 42 fmol/mg protein to 723 ± 54 after DHT (p < 0.02) as compared to 726 ± 39 and 627 ± 31 after testosterone and estradiol treatment. Reverse-phase high-performance liquid chromatography was performed on extracts of the MBH from individual castrated rats with and without DHT treatment in order to characterize the β-EP immunoactivity. The elution profile of the β-EP immunoactivity was very similar in both cases. Thus although DHT treatment is associated with a fall in the concentration of β-EP in the MBH, there does not appear to be a change in the processing of β-EP in the MBH. These results indicate that treatment with either testosterone or estradiol produces significant reductions in the hypothalamic concentrations of β-EP, CLIP, and α-MSH. The effectiveness of DHT in this respect demonstrates that there are independent androgen actions

ISSN:0028-3835    

DOI:10.1159/000124908

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

The role of protein kinase C in regulating Ca2 + channel activity was investigated using the whole-cell patch-clamp technique in the mouse pituitary tumor cell line AtT-20. The Ca2 + current was activated by depolarizing voltage steps from a holding potential of –80 mV. Extracellular application of the protein kinase C activator 1-oleoyl-2-acetylglycerol (OAG) reduced voltage-dependent Ca2 + current. This effect was reversible and dose dependent (10–100 µM). Pertussis toxin did not block the effect of OAG on Ca2 + current, suggesting that OAG does not affect Ca2 + channels via a pertussis toxin sensitive guanosine triphosphate binding protein. Na + -free solutions did not block the effect of OAG on Ca2 + channels, suggesting that this effect of OAG does not involve the Na+/H+ antiporter. The phorbol esters 12-deoxyphorbol-13-isobutyrate (10 µM) and phorbol-12,13-diacetate (100 µM) also reduced Ca2 + current. The results suggest that protein kinase C may be an inhibitory regulator of voltage-dependent Ca2 + ch

ISSN:0028-3835    

DOI:10.1159/000124909

出版商:S. Karger AG    

年代:1988

数据来源: Karger

摘要:

Two approximately equal subpopulations of corticotropin-releasing hormone (CRH)-containing parvocellular axons can be identified in the external zone of the median eminence in normal (unadrenalectomized) rats: one that contains pro-vasopressin (AVP)-derived peptides (i.e. AVP, AVP-associated neurophysin and the carboxy terminal glycopeptide) copackaged with CRH in secretory vesicles, and another that contains no detectable pro-AVP-derived peptides. In this study, antibodies to pro-AVP-derived peptides were used to demonstrate for the first time that similar subpopulations of CRH-containing parvocellular perikarya exist in the paraventricular nucleus of the hypothalamus in normal rats treated with colchicine. Electron-microscopic immunocytochemistry was performed on serial ultrathin sections to identify neurosecretory cell perikarya containing CRH that also expressed pro-AVP peptides or pro-oxytocin-derived neurophysin. Of the CRH-positive neurons that were detected, more than half stained positively for two pro-AVP peptides: AVP-associated neurophysin and the carboxy-terminal glycopeptide. Many of these cells also stained for AVP, but staining was variable, making quantitation of AVP-positive cells difficult. The remaining CRH-positive neurons contained no detectable pro-AVP peptides, and less than 0.5% of these CRH perikarya contained oxytocin-associated neurophysin. In the neurons that stained positively for both CRH and the pro-AVP peptides, CRH and the pro-AVP peptides were localized in the same secretory vesicles. The pro-AVP expressing and pro-AVP-deficient CRH neurons were distributed differently within the paraventricular nucleus. The results demonstrate that the CRH neurosecretory system in normal rats is comprised of major AVP-expressing and AVP-deficient neuronal subpopulations, distinguishable not only on the basis of peptide phenotype but also by the different topographical distributions of their perikarya.

ISSN:0028-3835    

DOI:10.1159/000124910

出版商:S. Karger AG    

年代:1988

数据来源: Karger