Induction of immediate–early gene expression in preoptic and hypothalamic neurons by the glucocorticoid receptor agonist, dexamethasone

Abstract

Glucocorticoid receptors (GR) exist in several preoptic and hypothalamic nuclei that participate in neuroendocrine control of anterior pituitary function. GR may mediate effects of endogenous steroids on hormone secretion, since intracerebral administration of exogenous ligands alters plasma levels of several pituitary hormones. The following studies utilized selective antisera for the transcriptional proteins, Fos and Jun, to examine whether these immediate–early gene products are upregulated in response to the GR agonist, dexamethasone (DEX). DEX was administered to groups of male rats by either a subcutaneous (s.c., 5.0 mg/kg) or intracerebroventricular route (i.c.v., 10.0 μg/rat); matched controls received vehicle only. Two hours later, the rats were sacrificed by transcardial perfusion, and serial 25 μm sections through the preoptic area and hypothalamus were processed by avidin–biotin immunocytochemistry 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 paraventricular nucleus. In the same group, Jun-li was detected only in the arcuate and suprachiasmatic nuclei. Subcutaneous injection of DEX resulted in more widespread immunostaining for Fos, which occurred in lateral, as well as medial, loci in the preoptic area and hypothalamus, whereas Jun-li was restricted to only medial sites. These data show that discrete populations of preoptic/hypothalamic neurons express c fos and/or jun in response to GR activation. The differential distribution of Fos-li following s.c. vs. i.c.v. administration of DEX suggests that steroid induction and/or amplification of this cellular signaling cascade may depend upon resultant hormone concentrations in neural tissue. In addition, the wide pattern of immunolabeling for Fos in the systematically treated group may reflect both central and peripheral (indirect) steroid effects. Additional studies are in progress to characterize those neurons within sites of neuroendocrine significance that exhibit possible upregulation of these regulatory gene products in response to GR stimulation.