Dehydroepiandrosterone stimulates the estrogen response element

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 62; no. 5; pp. 461 - 466
• Main Authors: Bruder, Jan M., Sobek, Lothar, Oettel, Michael
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.08.1997; Elsevier Science
• Subjects: Androstenedione - analogs & derivatives; Androstenedione - pharmacology; Animals; Aromatase Inhibitors; Biological and medical sciences; Cell Line; Cell receptors; Cell structures and functions; Dehydroepiandrosterone - metabolism; Dehydroepiandrosterone - pharmacology; Enzyme Inhibitors - pharmacology; Estradiol - analogs & derivatives; Estradiol - metabolism; Estradiol - pharmacology; Estrogen Antagonists - pharmacology; Fulvestrant; Fundamental and applied biological sciences. Psychology; Genes, Reporter; Genetic Vectors; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Humans; Luciferases - genetics; Mice; Molecular and cellular biology; Receptors, Estrogen - antagonists & inhibitors; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Transfection; Rodentia; Estrogen; Response element; Ovarian hormone; Vertebrata; Dehydroepiandrosterone; Regulation(control); Mammalia; Cell line; Mouse; Sex steroid hormone; Biological receptor; Hormonal receptor
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(97)00056-3

Studies suggest that the steroid, dehydroepiandrosterone (DHEA) can exert effects directly, in addition to its indirect role serving as a precursor for other steroids such as androgens and estrogens. Because DHEA is one of the most abundant adrenal steroids secreted in man, we investigated the functional activity of DHEA on the classic estrogen response element (ERE) in the presence of the estrogen receptor (ER) in transiently transfected cells. GT1-7 hypothalamic neuronal cells, devoid of the estrogen receptor, were transiently transfected with the estrogen receptor expression plasmid (HEGO) and the estrogen response element luciferase (ERELUC) reporter vector. As expected, a dose-response stimulation of luciferase activity was observed in cells treated with estradiol. Concentrations of estradiol from 10 −10–10 −6 M resulted in a 136–195 percent increase in luciferase activity compared with control. A dose-response stimulation was also observed in the cells treated with DHEA. A maximum stimulation of 177 percent increase in luciferase activity compared with control was observed with DHEA at a concentration of 10 −5 M. Both the estradiol and DHEA stimulation of ERE luciferase activity was inhibited by the estrogen receptor antagonist, ICI 182,780. The aromatase inhibitor, formestane in combination with estradiol or DHEA had no effect on luciferase activity, suggesting that the effect of DHEA is independent of its conversion to estadiol. Estradiol levels, as measured by ELISA, were appropriately elevated in the estradiol-treated cells but were not significantly different from the control cells in the DHEA-treated cells. These studies suggest a functional in vitro role of DHEA in activating the ERE in the presence of the classic ER.