Beyea Jason A, Olson David M, Harvey Steve
Department of Physiology and Perinatal Research Centre, University of Alberta, Edmonton, Alberta T6G2H7, Canada.
Dev Dyn. 2005 Apr;232(4):1037-46. doi: 10.1002/dvdy.20255.
It is now established that the lung is a target site for pituitary growth hormone (GH) action, because pathophysiological states of pituitary GH excess and deficiency are associated with impaired pulmonary function. The onset of lung development and differentiation is, however, before the ontogenic differentiation of pituitary somatotrophs. GH may be involved, nevertheless, in lung development, because it is present in extrapituitary tissues of preimplantation mouse embryos and in the lung buds of embryonic chickens. The possibility that GH may be expressed in the rat lung during fetal and neonatal development, therefore, has been assessed. GH mRNA was detected in the lung, and its 693-bp sequence was identical to that in the pituitary gland. By in situ hybridization, this transcript was found to be abundantly expressed in the lungs of embryonic day (ED) 17 rats in mesenchymal, mucosal epithelial, and smooth muscle cells. This transcript was expressed in neonates until at least day 14 postnatally and was localized to type I and II epithelial cells and to pulmonary tissue macrophages and alveolar macrophages. GH immunoreactivity paralleled GH mRNA cellular localization throughout the time course studied. This immunoreactivity was specific and was lost after antibody preabsorption. The perinatal and postnatal lung is, therefore, an extrapituitary site of GH gene expression during development. Given that the GH receptor is present in the lung from early development, lung GH may have autocrine and/or paracrine roles in lung growth or differentiation or in pulmonary function.
现已证实,肺是垂体生长激素(GH)发挥作用的靶器官,因为垂体GH分泌过多和不足的病理生理状态均与肺功能受损有关。然而,肺的发育和分化起始于垂体生长激素细胞的个体发生分化之前。尽管如此,GH可能参与肺的发育,因为它存在于植入前小鼠胚胎的垂体外组织以及胚胎鸡的肺芽中。因此,人们评估了GH在大鼠胎儿期和新生儿期肺中表达的可能性。在肺中检测到了GH mRNA,其693 bp的序列与垂体中的序列相同。通过原位杂交发现,该转录本在胚胎第17天(ED17)大鼠的肺间质、黏膜上皮和平滑肌细胞中大量表达。该转录本在新生儿期至少在出生后第14天仍有表达,且定位于I型和II型上皮细胞、肺组织巨噬细胞和肺泡巨噬细胞。在整个研究的时间进程中,GH免疫反应性与GH mRNA的细胞定位情况相符。这种免疫反应性具有特异性,在抗体预吸收后消失。因此,围产期和产后的肺是发育过程中GH基因表达的垂体外位点。鉴于从早期发育开始肺中就存在GH受体,肺GH可能在肺的生长、分化或肺功能中发挥自分泌和/或旁分泌作用。