COMPARATIVE DISTRIBUTION OF ESTROGEN RECEPTOR-ALPHA AND RECEPTOR-BETAMESSENGER-RNA IN THE RAT CENTRAL-NERVOUS-SYSTEM

Estrogen plays a profound role in regulating the structure and functio n of many neuronal systems in the adult rat brain. The actions of estr ogen were thought to be mediated by a single nuclear estrogen receptor (ER) until the recent cloning of a novel ER (ER-beta). To ascertain w hich ER is involved in the regulation of different brain regions, the present study compared the distribution of the classical (ER-alpha) an d novel (ER-beta) forms of ER mRNA-expressing neurons in the central n ervous system (CNS) of the rat with in situ hybridization histochemist ry. Female rat brain, spinal cord, and eyes were frozen, and cryostat sections were collected on slides, hybridized with [S-35]-labeled anti sense riboprobes complimentary to ER-alpha or ER-beta mRNA, stringentl y washed, and opposed to emulsion. The results of these studies reveal ed the presence of ER-alpha and ER-beta mRNA throughout the rostral-ca udal extent of the brain and spinal cord. Neurons of the olfactory bul b, supraoptic, paraventricular, suprachiasmatic, and tuberal hypothala mic nuclei, zona incerta, ventral tegmental area, cerebellum (Purkinje cells), laminae III-V, VIII, and IX of the spinal cord, and pineal gl and contained exclusively ER-beta mRNA. In contrast, only ER-alpha hyb ridization signal was seen in the ventromedial hypothalamic nucleus an d subfornical organ. Perikarya in other brain regions, including the b ed nucleus of the stria terminalis, medial and cortical amygdaloid nuc lei, preoptic area, lateral habenula, periaqueductal gray, parabrachia l nucleus, locus ceruleus, nucleus of the solitary tract, spinal trige minal nucleus and superficial laminae of the spinal cord, contained bo th forms of ER mRNA. Although the cerebral cortex and hippocampus cont ained both ER mRNAs, the hybridization signal for ER-alpha mRNA was ve ry weak compared with ER-P mRNA. The results of these in situ hybridiz ation studies provide detailed information about the distribution of E R-alpha and ER-beta mRNAs in the rat CNS. In addition, this comparativ e study provides evidence that the region-specific expression of ER-al pha, ER-beta, or both may be important in determining the physiologica l responses of neuronal populations to estrogen action. (C) Wiley-Liss , Inc.