Ontogeny of the GNRH-, glutaminase- and glutamate decarboxylase-gene expression in the hypothalamus of female rats.

Amino acid neurotransmitters like gamma-aminobutyric acid (GABA) and glutamate (GLU) are involved in the regulation of hypothalamic gonadotropin releasing hormone (GnRH) release. We investigated, whether there are changes of gene expression in the rat hypothalamus for GnRH, GnRH receptor, as well as glutaminase and glutamate decarboxylase, two enzymes regulating neurotransmitter concentrations of GLU and GABA in the brain during the ontogeny. After reverse transcription-polymerase chain reaction (RT-PCR) we used an ELISA method to quantify PCR products. In 15-day old animals high plasma luteinizing hormone (LH) levels with pronounced variations were found. In 25-day old animals LH values were low, whereas in 35-day old rats LH levels increased significantly indicating the reactivation of the GnRH-pulse generator at the beginning of puberty. In parallel to these changes, the mRNA levels of the GnRH receptor in the mediobasal hypothalamus were high at day 15, significantly lower at day 25 and again high at day 35 after birth (ELISA O.D. GnRH-R day 15: 0.46+/-0.07, day 25: 0.16+/-0.04, day 35: 0.36+/-0.04; p<0.01), but no changes of GnRH receptor gene expression were found in the preoptic area. The mRNA of GnRH in the preoptic area as well as mRNA levels of glutaminase and glutamate decarboxylase in the mediobasal hypothalamus and the preoptic area did not change during ontogeny. We conclude that hypothalamic GnRH receptors are involved in the characteristic changes of LH secretion patterns during sexual maturation. Major changes of GnRH receptor gene expression occurred in the mediobasal hypothalamus and correlated well with plasma LH levels, whereas hypothalamic mRNA levels of GnRH, glutaminase and glutamate decarboxylase did not change within the different age groups. Thus the activity of the GABA- and glutamatergic system during ontogeny may be regulated at the receptor or postreceptor level.