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 e strogens in the manifestation of affective disorders in women. The ana lysis of the mechanism of action of a number of antidepressant drugs c learly 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 r eceptor cDNA (SK-ER3). The present study shows that in SK-ER3 activati on of the estrogen receptor correlates with a marked decrease in monoa mine oxidase A activity. This effect is observed following treatment w ith a physiological concentration of 17 beta-estradiol and can be bloc ked by the specific antagonist of the steroid receptor, ICI 182,780. D ibutyryl cyclic AMP acting, like estrogens, on the state of differenti ation of SK-ER3 cells did not affect monoamine oxidase A activity. The present study provides strong evidence of a strict relationship betwe en estrogen receptor and monoamine oxidase A activity in human cells o f neural origin, thus favoring the hypothesis of an antidepressive eff ect of estrogens exerted via inhibition of the monoamine oxidative pat hway.