Effects of gonadal steroid hormones on GIRK2 gene transcription in the rat central nervous system

Abstract

GIRK(2) is the primary post-synaptic effector of opioids in the CNS that may contribute to the sex differences or age dependency in opioid analgesia. In the present study, we investigated the differential developmental and hormonal regulation of GIRK(2) gene transcription in rats. Male and female Wistar rats were divided into infant or adult intact, gonadectomized, sham and gonadectomy+testosterone groups. Semi-quantitative RT-PCR was used to determine the levels of GIRK(2) gene expression in spinal cord and brain. Our results showed that in male spinal cord/brain, the gene transcription of the infant group did not differ from expression levels of this gene in the gonadectomized or adult intact groups. Castration of males significantly decreased the expression levels of the GIRK(2) gene. Testosterone replacement in castrated rats did not raise GIRK(2) gene expression completely to the level of shams. In females however, a greater expression of GIRK(2) gene expression was found in adult intact or gonadectomized rats than in the infant groups. Ovariectomy failed to alter GIRK(2) mRNA levels significantly. No significant sex differences were observed in GIRK(2) gene transcription between intact, sham and infant groups, but gonadectomy produced sex differences in GIRK(2) gene transcription. The results strongly demonstrate the differential developmental and hormonal regulation of GIRK(2) in the rat CNS.