Vedder H, Parlow F, Zieglgänsberger W, Holsboer F
Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, FRG.
Exp Clin Endocrinol. 1993;101(3):161-5. doi: 10.1055/s-0029-1211224.
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.
脑源性甾体（神经甾体）构成了一类新的甾体，它们在脑细胞中独立于外周来源合成。虽然这些甾体的膜作用已得到一定程度的详细表征，但迄今为止它们的基因组效应研究较少。在本研究中，在无血清条件下且在严格控制的甾体水平下培养的垂体AtT 20细胞中，研究了神经甾体脱氢表雄酮、孕烯醇酮和孕烷醇酮对阿片促黑素皮质素原（POMC）基因表达的作用。在这些细胞中，已知POMC基因表达受肾上腺皮质糖皮质激素负调控。定量Northern印迹分析表明，即使在使用的最高浓度下，这些神经甾体或其共轭物均未影响POMC - mRNA水平。使用21 - OH甾体皮质酮作为对照，其显著抑制了POMC - mRNA的合成。这些结果表明，神经甾体在垂体促肾上腺皮质激素细胞水平上不控制POMC基因表达，并排除了这些化合物在糖皮质激素受体上的显著作用。
