ABSTRACT
Administration of 17beta-estradiol to ovariectomized rats increased the concentrations of galanin-like immunoreactivity (LI) in the hippocampal formation by 215% (P < 0.001) within 1 h. An increase of 125% (P < 0.05) was observed in the same brain region in the proestrous phase of a normal estrous cycle. Tamoxifen did not block the 17beta-estradiol-induced increase in the concentration of galanin-LI but resulted in a 62% decrease in the hypothalamus within 1 h. In vivo microdialysis in the dorsal hippocampal formation showed a decrease of extracellular galanin-LI (P < 0.001) 1-2 h after treatment with 17beta-estradiol, indicating a decreased release of galanin. For comparison, we studied the concentrations of neuropeptide Y, which were not influenced significantly in any of the regions studied. Taken together our results suggest that 17beta-estradiol inhibits galanin release, presumably from noradrenergic nerve terminals, and primarily via a nongenomic/indirect action, not necessarily involving the classical nuclear receptors ER-alpha or ER-beta. These rapid estrogen-induced changes in galanin release could influence transmitter signalling and plasticity in the hippocampal formation.
Subject(s)
Estradiol/pharmacology , Galanin/metabolism , Hippocampus/drug effects , Analysis of Variance , Animals , Brain/anatomy & histology , Brain/drug effects , Brain/metabolism , Chromatography, High Pressure Liquid/methods , Estradiol/blood , Estrous Cycle/drug effects , Estrous Cycle/physiology , Female , Hippocampus/metabolism , Immunohistochemistry/methods , In Situ Hybridization/methods , Microdialysis/methods , Neuropeptide Y/metabolism , Radioimmunoassay/methods , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
Tumor galanin content was measured in extracts from human pituitary adenomas using a specific RIA method for monitoring human galanin. Twenty-two out of twenty-four tumors contained galanin with notably high levels in corticotroph adenomas, varying levels in clinically inactive tumors, and low levels in GH secreting adenomas. Tumor galanin and ACTH contents were closely correlated in all tumors. In four young patients with microadenomas and highly active Mb Cushing tumor galanin was inversely related to tumor volume. The molecular form of tumor galanin, studied with reverse-phase HPLC, was homogeneous with the majority of tumor galanin coeluting with standard human galanin. In the tumors analysed with in situ hybridization there was a good correlation between galanin peptide levels and galanin mRNA expression. In some tumors galanin mRNA and POMC levels coexisted, in others they were essentially in different cell populations. Levels of plasma galanin-LI were not related to tumor galanin concentration, and galanin levels were in the same range in sinus petrosus close to the pituitary venous drainage as in peripheral blood. Corticotrophin releasing hormone injections in two patients caused ACTH, but no detectable galanin release into sinus petrosus. Our results demonstrate that corticotroph, but not GH adenomas, express high levels of galanin, in addition to ACTH, and that in some tumors both polypeptides are synthesised in the same cell population. However, galanin levels in plasma were not influenced by the tumor galanin content.
