Malendowicz L K, Andreis P G, Markowska A, Nowak M, Warchol J B, Neri G, Nussdorfer G G
Department of Histology and Embryology, School of Medicine, Poznan, Poland.
Res Exp Med (Berl). 1994;194(2):69-79. doi: 10.1007/BF02576368.
The acute effect of increasing concentrations (from 10(-8) to 10(-6) M) of neuromedin U-8 (NMU-8) on steroid secretion of rat adrenal gland was investigated in vitro by high-pressure liquid chromatography. The production of the following steroids was measured: pregnenolone (PREG), progesterone (PROG), 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO). NMU-8 had no effects on either dispersed adrenocortical cells or fragments of adrenocortical autotransplants lacking medullary chromaffin cells. Conversely, NMU-8 exerted concentration-dependent secretagogue effects on adrenal slices, including both cortex and medulla. At all concentrations tested, NMU-8 increased the production of both PREG and total post-PREG steroids. The increase in total post-PREG steroid output induced by low concentrations of NMU-8 (10(-8) M) was due to similar rises in the production of non-18-hydroxylated steroids (PROG, DOC and B) and 18-hydroxylated hormones (18OH-DOC, 18OH-B and ALDO); conversely, that provoked by higher concentrations of the neuropeptide (10(-7) to 10(-6) M) was almost exclusively caused by the rise in the yield of 18-hydroxylated steroids. The stimulating effect of NMU-8 on PREG output was blocked by both alpha-helical-CRH and corticotropin-inhibiting peptide, which are competitive inhibitors of CRH and ACTH, respectively. The following conclusions have been drawn: (1) NMU-8 affects adrenal steroid secretion indirectly by acting on the medullary chromaffin cells, which in turn may paracrinally stimulate the cortical ones; (2) at all concentrations tested, NMU-8, by stimulating the intramedullary CRH/ACTH system, causes a net rise in the activity of the early rate-limiting step of steroidogenesis, with the consequent increase in the output of the entire spectrum of post-PREG steroids; and (3) at higher concentrations (over 10(-8) M), NMU-8 also elicits the release from chromaffin cells of a factor (not yet known) that specifically enhances 18-hydroxylase activity.
采用高压液相色谱法在体外研究了神经降压素U-8（NMU-8）浓度增加（从10⁻⁸到10⁻⁶M）对大鼠肾上腺类固醇分泌的急性影响。检测了以下类固醇的生成：孕烯醇酮（PREG）、孕酮（PROG）、11-脱氧皮质酮（DOC）、皮质酮（B）、18-羟基-11-脱氧皮质酮（18OH-DOC）、18-羟基皮质酮（18OH-B）和醛固酮（ALDO）。NMU-8对缺乏髓质嗜铬细胞的分散肾上腺皮质细胞或肾上腺皮质自体移植片均无影响。相反，NMU-8对包括皮质和髓质的肾上腺切片具有浓度依赖性促分泌作用。在所有测试浓度下，NMU-8均增加了PREG和PREG后总类固醇的生成。低浓度NMU-8（10⁻⁸M）诱导的PREG后总类固醇产量增加是由于非18-羟基化类固醇（PROG、DOC和B）和18-羟基化激素（18OH-DOC、18OH-B和ALDO）生成的类似增加；相反，较高浓度神经肽（10⁻⁷到10⁻⁶M）引起的增加几乎完全是由18-羟基化类固醇产量的增加所致。NMU-8对PREG产量的刺激作用被α-螺旋促肾上腺皮质激素释放激素（CRH）和促肾上腺皮质激素抑制肽阻断，它们分别是CRH和促肾上腺皮质激素（ACTH）的竞争性抑制剂。得出以下结论：（1）NMU-8通过作用于髓质嗜铬细胞间接影响肾上腺类固醇分泌，而髓质嗜铬细胞反过来可能通过旁分泌刺激皮质细胞；（2）在所有测试浓度下，NMU-8通过刺激髓内CRH/ACTH系统，使类固醇生成早期限速步骤的活性净增加，从而导致PREG后所有类固醇的产量增加；（3）在较高浓度（超过10⁻⁸M）下，NMU-8还会引发嗜铬细胞释放一种因子（尚不清楚），该因子可特异性增强18-羟化酶活性。
