DISTRIBUTION AND PROPERTIES OF BRAIN GNRH RECEPTORS

The aim of the proposed studies to localize and characterize specific binding sites for gonadotropin releasing hormone (GnRH) in the central nervous system (CNS). Autoradiographic visualization of GnRH binding sites will be accomplished with [125I]-GnRH and analogs of GnRH, using both the thaw-mount autoradiographic technique and plastic section autoradiography. Membrane fractions from regions of high GnRH retention will be analyzed to determine the number, specificity, and binding characteristics of the GnRH binding sites. The properties of GnRH binding sites will be defined using radioligand assay techniques which are currently available for the study of pituitary GnRH receptors. Antisera to neurotransmitters and neuropeptides, such as dopamine-beta-hydroxylase, serotonin, substance P, enkephalin and neurotensin will be employed to determine the secretory products of GnRH target cells by means of immunohistochemistry. By this combination of anatomical and biochemical techniques, we propose to identify GnRH target sites within the CNS and to characterize both receptors and secretory products of the target cells. In view of the increase in the clinical use of GnRH for the treatment of secondary amenhorrea, cryptorchidism, delayed adolescence and regulation of the menstrual cycle, it is important to identify loci of potential side-effects which may be mediated through the CNS. Since the effects of GnRH within the brain may not be directly related to the reproductive system, the identification of GnRH-sensitive regions of the CNS will provide important clues regarding the nature of neurological side-effects which may result from GnRH administration.