Neurosteroids do not regulate proopiomelanocortin-gene expression in pituitary cells

Brain-derived steroids (neurosteroids) constitute a new group of steroids synthesized in brain cells independently from peripheral sources. While the membraneous actions of these steroids have been characterized in some detail, their genomic effects are less well studied up to now. In the present study, the action of the neurosteroids dehydroepiandrosterone, pregnenolone and pregnanolone on proopiomelanocortin (POMC)-gene expression was investigated in pituitary AtT 20 cells, which were cultured under serum-free conditions and at strictly controlled steroid levels. In these cells, POMC-gene expression is known to be negatively regulated by adrenocortical glucocorticoids. Quantitative Northern blot analysis showed that none of these neurosteroids or their conjugates affected POMC-mRNA levels even at the highest concentrations employed. The 21-OH steroid corticosterone was used as a control and markedly suppressed the synthesis of POMC-mRNA. These results suggest that neurosteroids do not control POMC-gene expression at the level of the pituitary corticotroph and exclude significant effects of these compounds at the glucocorticoid receptor.