| Pituitary growth hormone (GH) is an endocrine regulator of growth and development. However, due to the late ontogenetic appearance of the pituitary gland, and the late detection of GH in fetal circulation, pituitary GH cannot be involved in fetal or embryonic growth. This paradox may reflect the recent discovery that the GH gene is widely expressed in many extrapituitary tissues during organogenesis, in which it is thought to have local autocrine or paracrine actions that stimulate tissue proliferation and differentiation. Since the lung has been shown to express GH receptors (GHRs) prior to the ontogeny of pituitary somatotrophs, the possibility that the lung may be a site of GH production and action during early lung development has been examined.; Expression of GH mRNA was first evaluated in the developing chick lung. GH mRNA and protein were found to be expressed in mesenchymal and epithelial cells throughout embryonic development, declining near hatch, with the onset of pituitary GH secretion. GHR mRNA and protein were also found in the chick lung during the same period and in the same tissues, suggesting autocrine/paracrine roles of GH during lung development. The rat lung was also found to similarly express GH during the saccular and alveolar stages of development, when GHRs are also expressed. The possibility that lung GH may have autocrine/paracrine actions in the lung during perinatal development was therefore examined, using protein expression and a proteomics approach as a marker of GH action.; Altered GH signaling in the lung during the alveolarization period was achieved using intratracheal antisense oligodeoxynucleotides, to specifically downregulate lung GH expression, and by aerosolized GH transfected adenoviruses, to specifically overexpress the GH gene. Neonatal GHR knockout mice were also used as a model of GH deficiency. Changes in lung proteins, determined by 2D gel electophoresis and mass spectrometry, revealed roles of GH in the regulation of proliferative, metabolic, oxidative stress, and surfactant-related proteins in the lung during alveolarization.; These studies demonstrate the novel expression and action of GH in the developing lung and support the possibility that GH has important autocrine or endocrine roles in lung development. |
