Estrogenic control of monoamine oxidase A activity in human neuroblastoma cells expressing physiological concentrations of estrogen receptor.
Several lines of evidence support the hypothesis of a role played by estrogens in the manifestation of affective disorders in women. The analysis of the mechanism of action of a number of antidepressant drugs clearly demonstrated the involvement of the catecholaminergic system in the etiology of these complex behavioral pathologies. The present in vitro study was therefore undertaken to investigate the presence of a functional link between estrogen and catecholamine metabolism in cells of neural origin. The model system utilized was a human neuroblastoma cell line which was obtained by stable transfection of the estrogen receptor cDNA (SK-ER3). The present study shows that in SK-ER3 activation of the estrogen receptor correlates with a marked decrease in monoamine oxidase A activity. This effect is observed following treatment with a physiological concentration of 17 beta-estradiol and can be blocked by the specific antagonist of the steroid receptor, ICI 182,780. Dibutyryl cyclic AMP acting, like estrogens, on the state of differentiation of SK-ER3 cells did not affect monoamine oxidase A activity. The present study provides strong evidence of a strict relationship between estrogen receptor and monoamine oxidase A activity in human cells of neural origin, thus favoring the hypothesis of an antidepressive effect of estrogens exerted via inhibition of the monoamine oxidative pathway.
Milano Molecular Pharmacology Lab., Institute of Pharmacological Sciences, University of Milan, Italy.
Z Q
ZQ
Ma
E
E
Violani
F
F
Villa
G B
GB
Picotti
A
A
Maggi
D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007124:Immunoenzyme Techniques; D008995:Monoamine Oxidase / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D003994:Bucladesine; D008995:Monoamine Oxidase