Perroteau I, Netchitailo P, Homo-Delarche F, Delarue C, Lihrmann I, Leboulenger F, Vaudry H
Endocrinology. 1984 Nov;115(5):1765-73. doi: 10.1210/endo-115-5-1765.
The role of prostaglandins (PGs) in the regulation of glucocorticoid and mineralocorticoid production by the frog interrenal (adrenal) gland was studied in vitro by means of continuous perifusion. No change in corticosteroid production was observed upon perifusion with PGA1 or PGA2 (up to 10(-6) M). Conversely six other primary PGs, and the prostacyclin I2 (PGI2), significantly stimulated corticosteroidogenesis: the order of potency being PGE1 greater than PGI2 greater than PGE2 greater than PGB2 greater than PGB1 greater than PGF2 alpha greater than PGF1 alpha. The ability of the PGs to stimulate corticosterone and aldosterone production indicated that PGs may contribute to corticosteroid biosynthesis and that endogenous PGs could act as mediators for certain corticosteroid-stimulating factors. The essential role of endogenous PGs for spontaneous corticosteroid biosynthesis was demonstrated by the marked inhibition of corticosterone and aldosterone production induced by indomethacin (IDM) and meclofenamic acid, two specific inhibitors of cyclooxygenase which reduced significantly PG formation in the interrenal tissue. Stimulation of steroidogenesis by ACTH or cAMP was not affected by infusion of IDM or meclofenamic acid. In addition, ACTH did not modify the production of PGs by interrenal tissue. In contrast, the stimulatory effect of the angiotensin II analog [Sar1-Val5] AII, was markedly reduced in the presence of these two PG synthetase inhibitors and a direct stimulatory effect of the AII analog on PGE2 release was demonstrated. The effects of a supramaximal dose of [Sar1-Val5] AII could not be enhanced by PGE1 indicating that the corticosteroid response to angiotensin II is dependent upon endogenous PG synthesis, whereas the additivity of the stimulatory effects of PGE1 and a maximal dose of ACTH confirmed that PGs are not involved in the mechanism of action of ACTH. These results show that endogenous and exogenous PGs are implicated in corticosteroidogenesis in the frog. Since, in fish and amphibia the adrenocortical tissue is in close contact with the kidney (a major source of PGEs) these results may suggest a physiological relationship between the kidney and the interrenal gland in lower vertebrates. In addition, our results provide the first evidence that the action of angiotensin II on both corticosterone and aldosterone production may be mediated by PGs, whereas ACTH and cAMP stimulate corticosteroidogenesis through another mechanism. Thus, our data support the concept that ACTH and angiotensin II activate the early steps of corticosteroid biosynthesis via different pathways.
采用连续灌注法在体外研究了前列腺素（PGs）对青蛙肾上腺皮质激素和盐皮质激素分泌的调节作用。用PGA1或PGA2（浓度高达10⁻⁶ M）进行灌注时，未观察到皮质类固醇分泌有变化。相反，其他六种主要前列腺素以及前列环素I2（PGI2）能显著刺激皮质类固醇生成：其效力顺序为PGE1＞PGI2＞PGE2＞PGB2＞PGB1＞PGF2α＞PGF1α。PGs刺激皮质酮和醛固酮分泌的能力表明，PGs可能参与皮质类固醇的生物合成，内源性PGs可能作为某些皮质类固醇刺激因子的介质。消炎痛（IDM）和甲氯芬那酸是环氧化酶的两种特异性抑制剂，它们能显著减少肾上腺组织中PG的生成，从而证明了内源性PGs对自发性皮质类固醇生物合成的重要作用。IDM或甲氯芬那酸的灌注不影响促肾上腺皮质激素（ACTH）或环磷酸腺苷（cAMP）对类固醇生成的刺激作用。此外，ACTH不会改变肾上腺组织中PGs的分泌。相反，在这两种PG合成酶抑制剂存在的情况下，血管紧张素II类似物[Sar1-Val5]AII的刺激作用明显减弱，并且证明了AII类似物对PGE2释放有直接刺激作用。PGE1不能增强超最大剂量的[Sar1-Val5]AII的作用，这表明对血管紧张素II的皮质类固醇反应依赖于内源性PG合成，而PGE1和最大剂量ACTH的刺激作用具有相加性，这证实了PGs不参与ACTH的作用机制。这些结果表明，内源性和外源性PGs都参与了青蛙的皮质类固醇生成。由于在鱼类和两栖动物中，肾上腺皮质组织与肾脏（PGEs的主要来源）紧密接触，这些结果可能提示了低等脊椎动物中肾脏与肾上腺之间的生理关系。此外，我们的结果首次证明血管紧张素II对皮质酮和醛固酮分泌的作用可能由PGs介导，而ACTH和cAMP通过另一种机制刺激皮质类固醇生成。因此，我们的数据支持了ACTH和血管紧张素II通过不同途径激活皮质类固醇生物合成早期步骤的观点。
