Effect of Gonadal Steroid Hormones on GIRK2 Gene Transcription in Rat's Spinal Cord

Considerable evidences have indicated the differences between different sexes in their pain responses and opioid antinociception in which Opioids have been more potent in males than females. GIRK2, the primary post-synaptic effectors of opioids in the CNS, possibly contributes in these sex-related differences. In the present study, we examined the role and effect of gonadal steroid hormones on GIRK2 gene transcription in rats.

Male and female Wistar rats were divided into four groups of intact infant or adult, GDX, sham and GDX+T groups. ˝semiquantitave RT-PCR˝ was used to determine the GIRK2 gene expression in spinal cord tissue of the rats.

Our results showed that in the spinal cord of male rats, gene transcription of infant group did not fluctuate along with expression level of this gene in GDX or adult intact groups. Elimination of gonadal hormones in male rats significantly decreased the expression level of GIRK2 gene. These changes were not restored by testosterone replacement. However, in females, a greater expression of GIRK2 gene was found in intact adult or GDX rats than those of infants. Ovariectomy of animals failed to alter the GIRK2 mRNA level. No significant preferential differences were observed in GIRK2 gene transcription between both sexes of intact, sham and infant groups.

These findings show that regulation of GIRK2 gene transcription by gonadal hormones is male-dominant. Whereas, other sex-dependent developmental factors prominently affect on GIRK2 gene transcription in female animals. Further investigations are needed to clarify the exact mechanism.