Identification and characterization of estrogen receptor alpha-containing neurons projecting to the vicinity of the gonadotropin-releasing hormone perikarya in the rostral preoptic area of the rat

Gonadal steroids exert a powerful regulatory influence upon the functioning of gonadotropin-releasing hormone (GnRH) neurons despite the apparent abse nce of gonadal steroid receptors in these cells. By using retrograde-tracin g techniques combined with dual-labeling immunocytochemistry, we show here that distinct populations of estrogen receptor alpha (ER alpha)-containing neurons located in the hypothalamus and caudal brainstem project to the vic inity of the GnRH perikarya located in the rostral preoptic area (rPOA). Th e strongest estrogen-receptive afferent projection to this area originated from neurons located in the anteroventral periventricular and medial preopt ic nuclei of the preoptic area. Approximately 50% of arcuate nucleus neuron s projecting to the rPOA were demonstrated to synthesize either neuropeptid e Y or beta-endorphin, but little evidence was found for ERa immunoreactivi ty in either of these specific subpopulations. Over 80% of all tyrosine hyd roxylase-expressing neurons in the arcuate nucleus expressed ER alpha, but none projected to the rPOA. In the caudal brainstem, the A1 and A2 norepine phrine neurons comprised nearly all of the retrogradely labeled neurons. Ho wever, only the A2 afferents expressed ERa immunoreactivity, whereas the A1 afferents coexpressed neuropeptide Y. These observations, combined with th e anterograde labeling data of others, provide neuroanatomical evidence for the existence of specific estrogen-receptive neuronal cell populations tha t project to the rPOA and may be involved in the estrogen-dependent transsy naptic regulation of GnRH neurons in the rat. (C) 1999 Wiley-Liss, Inc.