神经介素U增强大鼠促肾上腺皮质激素刺激的肾上腺皮质细胞的增殖。

Trejter Marcin, Guidolin Diego, Nowak Magdalena, Macchi Veronika, Majchrzak Mariola, De Caro Raffaele, Malendowicz Ludwik K

Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan PL-60781, Poland.

Int J Mol Med. 2009 Jan;23(1):99-104.

Neuromedin U (NMU) is a brain-gut peptide involved in the regulation of the hypothalamic-pituitary-adrenal axis and adrenocortical cell proliferation. In this study, we investigated the effects of NMU8 (three subcutaneous injections of 6.0 nmol/100 g, 24, 16 and 8 h before autopsy) on the adrenal glands of rats treated for 2 or 4 days with a low (2 microg/100 g body weight/24 h) or a high (8 microg) dose of adrenocorticotropic hormone (ACTH). As revealed by RT-PCR, ACTH treatment did not prevent expression of NMUR1 in rat adrenal cortex. At day 4 of ACTH administration, the weight of adrenals was lower than at day 2. NMU8 administration prevented ACTH-induced increases of adrenal weight at day 2 of the experiment. ACTH plasma concentrations were increased in all ACTH-administered rats. NMU8 administration increased ACTH plasma concentration at day 2 of the lower ACTH dose-treated group while it reduced the ACTH plasma level at day 4 in the higher ACTH dose-administered rats. In all groups of ACTH-treated rats, NMU8 changed neither aldosterone nor corticosterone plasma concentrations. In the zona glomerulosa (ZG), NMU8 increased metaphase index at days 2 and 4 in the lower ACTH dose-treated group and had no statistically significant effect in rats treated with the higher ACTH dose. In the zona fasciculata (ZF), NMU8 administration increased metaphase index at day 2 in the lower ACTH dose-treated group but reduced metaphase index at day 4 in the higher dose ACTH-administered rats. NMU8 reduced the number of cells per unit area both in ZG and ZF at day 2 in the higher ACTH dose-treated rats. In the remaining groups NMU8 did not produce statistically significant changes in the number of cells per unit area. Thus, our findings demonstrate that exogenous NMU may stimulate proliferation primarily of the cortical ZG cells in rats administered with ACTH, although at high doses of exogenous corticotropin an opposite effect occurred.

神经介素U（NMU）是一种脑肠肽，参与下丘脑-垂体-肾上腺轴的调节及肾上腺皮质细胞增殖。在本研究中，我们调查了NMU8（在尸检前24、16和8小时皮下注射3次，每次6.0 nmol/100 g）对用低剂量（2 μg/100 g体重/24小时）或高剂量（8 μg）促肾上腺皮质激素（ACTH）处理2天或4天的大鼠肾上腺的影响。逆转录聚合酶链反应（RT-PCR）结果显示，ACTH处理并未阻止大鼠肾上腺皮质中NMU受体1（NMUR1）的表达。在给予ACTH的第4天，肾上腺重量低于第2天。在实验第2天，给予NMU8可阻止ACTH诱导的肾上腺重量增加。所有给予ACTH的大鼠血浆ACTH浓度均升高。在低剂量ACTH处理组第2天给予NMU8可增加血浆ACTH浓度，而在高剂量ACTH处理的大鼠中，第4天给予NMU8可降低血浆ACTH水平。在所有给予ACTH处理的大鼠组中，NMU8均未改变醛固酮和皮质酮的血浆浓度。在球状带（ZG），低剂量ACTH处理组在第2天和第4天NMU8增加了中期指数，而在高剂量ACTH处理组大鼠中无统计学显著影响。在束状带（ZF），低剂量ACTH处理组第2天给予NMU8增加了中期指数，但高剂量ACTH处理的大鼠第4天中期指数降低。在高剂量ACTH处理的大鼠第2天，NMU8减少了ZG和ZF中每单位面积的细胞数量。在其余组中，NMU8未对每单位面积的细胞数量产生统计学显著变化。因此，我们的研究结果表明，外源性NMU可能主要刺激给予ACTH的大鼠皮质ZG细胞的增殖，尽管在高剂量外源性促肾上腺皮质激素时会出现相反的效果。