INDUCTION OF IMMEDIATE-EARLY GENE-EXPRESSION IN PREOPTIC AND HYPOTHALAMIC NEURONS BY THE GLUCOCORTICOID RECEPTOR AGONIST, DEXAMETHASONE

Glucocorticoid receptors (GR) exist in several preoptic and hypothalam ic nuclei that participate in neuroendocrine control of anterior pitui tary function. GR may mediate effects of endogenous steroids on hormon e secretion, since intracerebral administration of exogenous ligands a lters plasma levels of several pituitary hormones. The following studi es utilized selective antisera for the transcriptional proteins, Fos a nd Jun, to examine whether these immediate-early gene products are upr egulated in response to the GR agonist, dexamethasone (DEX). DEX was a dministered to groups of male rats by either a subcutaneous (s.c., 5.0 mg/kg) or intracerebroventricular route (i.c.v., 10.0 mu g/rat); matc hed controls received vehicle only. Two hours later, the rats were sac rificed by transcardial perfusion, and serial 25 mu m sections through the preoptic area and hypothalamus were processed by avidin-biotin im munocytochemistry for Fos-and Jun-like proteins. Animals treated with DEX i.c.v. exhibited Fos-like immunoreactivity (-li) in several sites in close proximity to the third ventricle, including the preoptic and anterior hypothalamic nuclei, and the periventricular zone of the para ventricular nucleus. In the same group, Jun-ii was detected only in th e arcuate and suprachiasmatic nuclei. Subcutaneous injection of DEX re sulted in more widespread immunostaining for Fos, which occurred in la teral, as well as medial, loci in the preoptic area and hypothalamus, whereas Jun-ii was restricted to only medial sites. These data show th at discrete populations of preoptic/hypothalamic neurons express c fos and/or jun in response to GR activation. The differential distributio n of Fos-Ii following s.c. vs. i.c.v. administration of DEX suggests t hat steroid induction and/or amplification of this cellular signaling cascade may depend upon resultant hormone concentrations in neural tis sue. In addition, the wide pattern of immunolabeling for Fos in the sy stematically treated group may reflect both central and peripheral (in direct) steroid effects. Additional studies are in progress to charact erize those neurons within sites of neuroendocrine significance that e xhibit possible upregulation of these regulatory gene products in resp onse to GR stimulation. (C) 1997 Elsevier Science B.V.