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Estrogen Receptor (ER), But Not ERß, Gene Is Expressed in Growth Hormone-Releasing Hormone Neurons of the Male Rat Hypothalamus¹

Department of Medicine, Nippon Medical School, Tokyo 113-8603, Japan

Address all correspondence and requests for reprints to: Jun Kamegai, M.D., Department of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8603, Japan. E-mail: jkamegai{at}nms.ac.jp

GH synthesis and release from pituitary somatotropes is controlled by the opposing actions of the hypothalamic neuropeptides, GH-releasing hormone (GHRH), and somatostatin (SS). There is a striking sex difference in the pattern of GH secretion in rats. Early reports indicate that gonadal steroids have important imprinting effects during the neonatal period. Recently, our laboratory and others have reported that the GH secretory pattern is altered by short-term gonadal steroid treatment in adult rat, suggesting that gonadal steroids are also important determinants of the pattern of GH secretion during adult life. However, the site of action of gonadal steroids in the adult rat hypothalamus is still unknown. In this study, we used in situ hybridization in the adult male rat brain to determine whether GHRH neurons and/or SS neurons coexpress estrogen receptor (ER) and ERß genes. In the medial basal hypothalamus of adult male rat, the ER messenger RNA (mRNA) was located in medial preoptic area (MPA) and arcuate nucleus (ARC), whereas ERß mRNA was detected in MPA, supraoptic nucleus, and paraventricular nucleus. From studies using adjacent sections, the distribution of ER mRNA-containing cells appeared to overlap in part with those of GHRH and SS expressing cells only in the ARC. On the other hand, the distribution of ERß mRNA-containing cells does not appear to overlap with GHRH cells or SS cells. The double label in situ hybridization studies showed that in the ARC, 70% of GHRH neurons contain ER mRNA, whereas less than 5% of SS neurons expressed the ER gene. These results indicated that GHRH neurons are direct target cells for estrogens, and estrogens may act directly on GHRH neurons through ER during adult life to modify GH secretory patterns.

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