Effect of adrenal steroids on preproneurokinin-A gene expression in discrete regions of the rat brain.

An in situ hybridization histochemical procedure was developed to monitor the cellular distributions of the three major alternatively spliced alpha, beta and gamma species of mRNA encoding neurokinin molecules of the CNS. Two oligodeoxyribonucleotide probes were synthesized corresponding to common sequences of the alpha, beta, and gamma NK-A mRNA. The first experiment used rats that were sham-operated (Sham), adrenalectomized (ADX), and ADX rats treated with corticosterone (ADX+CORT). Intense labelling was observed within the habenula (Hb), while strong labelling was detected within the olfactory tubercle (OT), the lateral olfactory tubercle (LOT), the horizontal diagonal band of Broca (HDB), the bed nucleus of the stria terminalis (BNST), and the dorsal and ventral part of the caudate putamen (d-CP, v-CP). Moderate labelling of a number of cells was observed within the medial preoptic area (mPOA), the postero-dorsal part of the medial amygdala (MePD), and the dorsal and ventral part of the premamillary nucleus of the hypothalamus (PM-D; PM-V). ADX decreased NK-A mRNA in OT, LOT, HDB, BNST, CP compared to sham-operated rats, whereas CORT replacement elevated NK-A mRNA to above sham levels in OT, LOT, HDB, BNST and CP. There was no effect of ADX or CORT in Hb, while smaller, and often non-significant, effects of ADX and CORT replacement were found in other areas. Since there are two types of adrenal steroid receptors in brain, we next investigated the effects of agonists for type I and type II adrenal steroid receptors. ADX rats were given either aldosterone (ALDO, 10 micrograms/ml/h, Alzet minipumps) or RU 28362 (10 micrograms/ml/h, Alzet minipumps) for 8 days. Type I receptor activation by ALDO partially reversed the ADX-induced decrease in NK-A mRNA, whereas type II steroid receptor activation by RU 28362 restored the decrease caused by ADX and caused an elevation of NK-A mRNA above sham levels in OT. These findings show that adrenal steroids regulate NK-A gene expression through both type I and type II receptors in a number of brain areas. The results are consistent with a role for adrenal steroids and neurokinins in the regulation of body fluid homeostasis.