Activation of gene expression of the gamma-aminobutyric acid rather than the glutamatergic system in the preoptic area during the preovulatory gonadotropin surge of the rat

There is increasing evidence that in the rat prior to and during the preovu latory LH surge, release rates of GABA in the preoptic area (POA) are decre ased while no such changes occurred in the mediobasal hypothalamus (MBH). I n addition, GnRH release appears to be facilitated by an increased preoptic excitation of glutamate (GLU). To investigate whether such changes of secr etory activity of intrahypothalamic GABA or GLU neurons are associated with altered gene expression of biosynthetic enzymes or transporter proteins ch aracteristic for either neuronal system, we determined mRNA levels of the t wo forms of the GABA-synthesizing enzyme glutamate decarboxylase (GAD65 and GAD67), the glutamate-synthesizing enzyme glutaminase (GLS), the GABA tran sporter type 1 (GAT-1) and the glutamate-aspartate transporter type 1 (GLAS T), Competitive RT-PCRs using mutant cRNAs as internal standards were condu cted with mRNA extracted from microdissected tissue of POA and MBH from die strous, proestrous, and estrous rats. Proestrous animals were subgrouped ac cording to their endocrine status as follows: 'prior to', on Phe 'ascending ' or on the 'descending' limb of the LH peak, and 'after the LH surge. (pos t)'. During the preovulatory LH surge, mRNA concentrations of GAD67 and GAT -1 in the POA were significantly increased compared to those observed on di estrous (2.8-fold for GAD67(-) and 2.5-fold for GAT-1, p < 0.01), while in the MBH the amount of both mRNAs remained constant. The expression levels o f GAD65, GLS and GLAST were without any changes in the POA as well as in th e MBH. These findings support the hypothesis that in rats induction of the preovulatory LH surge is controlled at the level of GnRH perikarya, and sug gest that altered activities of intrapreoptic GABA neurons at both transcri ptional and secretory levels are pivotal for the preovulatory activation of GnRH neurons. Copyright (C) 2000 S. Karger AG, Basel.