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 moni tor the cellular distributions of the three major alternatively splice d alpha, beta and gamma species of mRNA encoding neurokinin molecules of the CNS. Two oligodeoxyribonucleotide probes were synthesized corre sponding to common sequences of the alpha, beta, and gamma NK-A mRNA. The first experiment used rats that were sham-operated (Sham), adrenal ectomized (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 v entral 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 dorsa l. and ventral part of the premamillary nucleus of the hypothalamus (P M-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 o f ADX or CORT in Hb, while smaller, and often non-significant, effects of ADX and CORT replacement were found in other areas. Since there ar e two types of adrenal steroid receptors in brain, we next investigate d the effects of agonists for type I and type II adrenal steroid recep tors. ADX rats were given either aldosterone (ALDO, 10 mu g/ml/h, Alze t minipumps) or RU 28362(10 mu g/ml/h, Alzet minipumps) for 8 days. Ty pe I receptor activation by ALDO partially reversed the ADX-induced de crease 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 st eroids regulate NK-A gene expression through both type I and type II r eceptors in a number of brain areas. The results are consistent with a role for adrenal steroids and neurokinins in the regulation of body f luid homeostasis.