Effect of GABAergic compounds on gonadotropin-releasing hormone receptor gene expression in the rat

Using a competitive reverse transcription-polymerase chain reaction (RT-PCR), the amounts of GnRH receptor (GnRHR) transcript in a discrete nucleus micropunched from rat brain slices were determined. GnRHR transcript was highly expressed in anterior pituitary ≫ median eminence > posterior mediobasal hypothalamus (pMBH) > preoptic area (POA) but not in cortex and posterior pituitary, which were used as control tissues. To examine the effect of GABA on GnRHR transcript level, 10 nmol of muscimol, a GABA-A receptor agonist, or baclofen, a GABA-B receptor agonist, was microinjected into the lateral ventricle of ovariectomized rats. Two hours after an intraventricular injection, rats were decapitated. Blood was collected 1 h before and after drug administration and used for LH determination. Serum LH levels were significantly reduced by muscimol but not by baclofen within 2 h. The activation of GABA-A receptors with muscimol resulted in a significant inhibition in GnRHR transcript level in both the pMBH and POA but not in the pituitary. The activation of GABA-B receptors with baclofen, however, did not produce any effect on GnRHR transcript level in the pMBH and POA, as well as the pituitary. This experiment demonstrates for the first time that GABAergic neurotransmission, through GABA-A receptors, is involved in the regulation of GnRHR transcript level in the rat hypothalamus. This suggests that GABAergic neurotransmission regulates GnRHR gene expression in a coordinated, yet complex, fashion in the control of the neuroendocrine function of GnRH-LH axis.