ONTOGENY OF THE GNRH-GENE, GLUTAMINASE-GENE AND GLUTAMATE DECARBOXYLASE-GENE EXPRESSION IN THE HYPOTHALAMUS OF FEMALE RATS

Amino acid neurotransmitters like gamma-aminobutyric acid (GABA) and g lutamate (GLU) are involved in the regulation of hypothalamic gonadotr opin 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 enzy mes regulating neurotransmitter concentrations of GLU and GABA in the brain during the ontogeny. After reverse transcription-polymerase chai n 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 wer e low, whereas in 35-day old rats LH levels increased significantly in dicating 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, signific antly 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 on togeny. We conclude that hypothalamic GnRH receptors are involved in t he characteristic changes of LH secretion patterns during sexual matur ation. Major changes of GnRH receptor gene expression occurred in the mediobasal hypothalamus and correlated well with plasma LH levels, whe reas hypothalamic mRNA levels of GnRH, glutaminase and glutamate decar boxylase did not change within the different age groups. Thus the acti vity of the GABA- and glutamatergic system during ontogeny may be regu lated at the receptor or postreceptor level. (C) 1998 Elsevier Science B.V. All rights reserved.