Sex steroid regulation of glutamate decarboxylase mRNA expression in goldfish brain is sexually dimorphic

Testosterone and oestradiol can modulate GABA synthesis in sexually regress ed goldfish. Here we investigated their effects on the mRNA expression of t wo isoforms of the GABA synthesizing enzyme glutamate decarboxylase (GAD(65 ) and GAD(67), EC 4.1.1.15). Full-length GAD clones were isolated from a go ldfish cDNA library and sequenced. Goldfish GAD(65) encodes a polypeptide o f 583 amino acid residues, which is 77% identical to human GAD(65). Goldfis h GAD(67) encodes a polypeptide of 587 amino acid residues and is 82% ident ical to human GAD(67). Goldfish GAD(65) and GAD(67) are 63% identical. Sexu ally regressed male and female goldfish were implanted with solid silastic pellets containing testosterone, oestradiol or no steroid. Semiquantitative PCR analysis showed that oestradiol significantly increased GAD(65) mRNA e xpression in female hypothalamus and telencephalon, while testosterone resu lted in a significant increase only in telencephalon. GAD(67) mRNA levels w ere not affected by steroids in females. In contrast, both steroids induced significant decreases of GAD(65) and GAD(67) mRNA levels in male hypothala mus, but had no effect on GAD mRNA expression in male telencephalon.. Our r esults indicate that modulation of GAD mRNA expression is a possible mechan ism for steroid action on GABA synthesis, which may have opposite effects i n males and females.