Ramachandran J, Kong Y C, Liles S
Acta Endocrinol (Copenh). 1976 Jul;82(3):587-99. doi: 10.1530/acta.0.0820587.
Both ACTH and NPS-ACTH in which the single tryptophan residue of the hormone is modified were able to stimulate adrenal corticosterone concentration to the same extent in hypophysectomized rats, although a higher dose of NPS-ACTH was required. ACTH stimulated adrenal cyclic AMP levels 120-fold in hypophysectomized rats whereas NPS-ACTH caused a marginal increase. In the case of ACTH, low doses of the hormone capable of producing maximal stimulation of corticosterone synthesis did not produce any detectable change in cyclic AMP concentration. The rates of secretion of corticosterone induced by ACTH and NPS-ACTH in vivo were the same. NPS-ACTH was found to be 1.2% as potent as ACTH. The role of cyclic AMP in adrenal repair was investigated by administering equipotent doses of ACTH or NPS-ACTH to hypophysectomized rats. In adult rats both failed to produce a significant increase in adrenal weight. Adrenal function (measured by responsiveness to exogenous ACTH in vitro) was restored by NPS-ACTH but not to the same degree as ACTH. In hypophysectomized weanling rats, ACTH produced a small but significant increase in adrenal weight but NPS-ACTH did not. These results suggest that an increase in adrenal cyclic AMP may not be obligatory for the stimulation of steroidogenesis by ACTH and that some of the trophic actions of the hormone may be mediated by cyclic AMP.
促肾上腺皮质激素（ACTH）和对激素中单个色氨酸残基进行修饰的NPS-ACTH，在垂体切除的大鼠中均能同等程度地刺激肾上腺皮质酮浓度升高，尽管所需的NPS-ACTH剂量更高。ACTH可使垂体切除大鼠的肾上腺环磷酸腺苷（cAMP）水平升高120倍，而NPS-ACTH仅引起轻微升高。就ACTH而言，能够最大程度刺激皮质酮合成的低剂量激素并未使cAMP浓度产生任何可检测到的变化。ACTH和NPS-ACTH在体内诱导的皮质酮分泌速率相同。发现NPS-ACTH的效力仅为ACTH的1.2%。通过给垂体切除的大鼠给予等效剂量的ACTH或NPS-ACTH，研究了cAMP在肾上腺修复中的作用。在成年大鼠中，两者均未能使肾上腺重量显著增加。NPS-ACTH可恢复肾上腺功能（通过体外对外源性ACTH的反应性来衡量），但恢复程度不及ACTH。在垂体切除的断奶大鼠中，ACTH可使肾上腺重量有小幅但显著的增加，而NPS-ACTH则无此作用。这些结果表明，ACTH刺激类固醇生成时，肾上腺cAMP升高可能并非必需，且该激素的一些营养作用可能由cAMP介导。
