Estrogen receptor (ER)alpha, but not ER beta, gene is expressed in growth hormone-releasing hormone neurons of the male rat hypothalamus

GH synthesis and release from pituitary somatotropes is controlled by the o pposing actions of the hypothalamic neuropeptides, GH-releasing hormone (GH RH), and somatostatin (SS). There is a striking sex difference in the patte rn of GH secretion in rats. Early reports indicate that gonadal steroids ha ve important imprinting effects during the neonatal period. Recently, our l aboratory and others have reported that the GH secretory pattern is altered by short-term gonadal steroid treatment in adult rat, suggesting that gona dal 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 hy bridization in the adult male rat brain to determine whether GHRH neurons a nd/or SS neurons coexpress estrogen receptor alpha (ER alpha) and ER beta g enes. In the medial basal hypothalamus of adult male rat, the ER alpha mess enger RNA (mRNA) was located in medial preoptic area (MPA) and arcuate nucl eus (ARC), whereas ER beta mRNA was detected in MPA, supraoptic nucleus, an d paraventricular nucleus. From studies using adjacent sections, the distri bution of ER alpha mRNA-containing cells appeared to overlap in part with t hose of GHRH and SS expressing cells only in the ARC. On the other hand, th e distribution of ER beta 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 ERa mRNA, whereas less than 5% of SS neurons expressed the ER alpha gene. These results indicated that GHRH neurons are direct target cells for estrogens, and estrogens may act directly on GHRH neurons through ER alpha during adult life to modify GH secretory patterns.