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Estradiol Induces Galanin Gene Expression in the Pituitary of the Mouse in an Estrogen Receptor Alpha-Dependent Manner

Peptide Pharmacology and Functional Morphology Sections, Women’s Health Research Institute, Wyeth-Ayerst Research, Radnor, Pennsylvania 19087

Address all correspondence and requests for reprints to: Francisco J. Lopez, Ligand Pharmaceuticals, Inc., Endocrinology and CNS Pharmacology, 10275 Science Center Drive, San Diego, California 92121.

Estradiol imprinting plays an important role in the regulation of galanin (GAL) gene expression in the rat. In the anterior pituitary gland, GAL gene expression is greatly induced by estrogen. The relative involvement that the two estrogen receptor subtypes, and ß, have in regulating this induction is not known. We have utilized ER-knock-out (ERKO) mice to discriminate the roles of ER and ERß in the regulation of GAL gene expression in the anterior pituitary gland. Our goals were to measure the effects of estradiol on GAL gene expression by solution hybridization ribonuclease protection assay in wild-type mice and to determine the roles of ER and, indirectly, ERß by measuring the same response in the ERKO mice. Estradiol treatment for one week elevated GAL gene expression 30–40 fold in the wild-type mouse pituitary. Evaluation of estrogen effects on GAL gene expression in the anterior pituitary of ERKO animals revealed that ER is essential, because no response to estrogen was observed in these animals. Since ERß mRNA was identified in the anterior pituitary by RT-PCR, but estrogen had no effects on GAL gene expression in the ERKO mice, the ß subtype of ER does not appear to participate in estrogen-evoked GAL gene expression in the mouse anterior pituitary.

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