Biological activity of adrenocorticotropic hormone precursors on ovine adrenal cells.
Biological activity of adrenocorticotropic hormone precursors on ovine adrenal cells.
复制标题
促肾上腺皮质激素前体对绵羊肾上腺细胞的生物活性。
DOI：
10.1152/ajpendo.1995.268.4.e623
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
White,A
中科院分区：
文献类型：
--
作者：
Schwartz,J;Kleftogiannis,F;Jacobs,R;Thorburn,GD;Crosby,SR;White,A
Adrenocorticotropic hormone (ACTH) is synthesized in the corticotrophs as a precursor, pro-opiomelanocortin (POMC), which is processed via proACTH to ACTH. Both precursors and ACTH are secreted. Although the steroidogenic activity of ACTH is well characterized, that of the precursors is not. This study assessed the capacity of POMC and proACTH to alter cortisol synthesis. POMC and proACTH were prepared by subjecting medium, conditioned by exposure to DMS-79 cells, to Sephadex chromatography, and the bioactivity was assessed in cultured-dissociated ovine adrenal cells. Alone neither POMC (< or = 2.6 nM) nor proACTH (< or = 0.7 nM) showed any consistent acute (6 h) stimulatory or inhibitory action on cortisol in either fetal or adult cells. In contrast, in fetal cells the precursors inhibited steroidogenic response to ACTH-(1-24). POMC at 2.6 nM, but not lower concentrations, decreased the cortisol responses to 0.01, 0.1, and 1 nM ACTH by at least 50%. ProACTH (0.70 and 0.23 nM) decreased the responses to ACTH at 0.01 nM by 89 and 67%, respectively, and at 0.1 nM by 49 and 34%, respectively. At 1 nM ACTH only 0.7 nM proACTH decreased the response to ACTH (by 69%). In contrast, in adult adrenal cells, the precursors did not significantly reduce the response to ACTH (range 0.01-1 nM). Therefore, these data indicate that POMC and proACTH can inhibit the cortisol response to ACTH in fetal adrenal cells, an effect that is concentration dependent. The data suggest that precursors may play a physiological role, possibly regulating fetal plasma cortisol concentrations.
