Growth hormone expression in the perinatal and postnatal rat lung

Abstract

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.

Growth hormone (GH) action in the developing lung: Changes in lung proteins after adenoviral GH overexpression

“…As the expression of the Adv was confined to the lung, its overexpression is likely to reflect the actions of endogenous GH produced in the lung. These results, therefore, support the possibility (Beyea et al, 2005) that GH expression during alveolarization promotes autocrine/paracrine actions involved in lung function. …”

“…This protein is known to be locally expressed within the fetal lung and is believed to be produced in alveolar Type II epithelial cells in response to infection (Yang et al, 1995). It is pertinent, therefore, that GH and has cytokine actions (Waters et al, 1999) and is also produced in Type II epithelial cells (Beyea et al, 2005). An inhibitory effect of GH on haptoglobin production is also indicated by the decrease in serum haptoglobin levels in response to recombinant human GH treatment in burn-victim rats (Jeschke et al, 1999).…”

“…Adenoviral delivery of genes directly to the lungs by this technique has been shown not to affect mortality, lung toxicity, or inflammation of the lungs (Kanaan et al, 2002;Pozeg et al, 2003). The pups were killed when they were 14 days old, at the end of the alveolarization period, at a time when the lung expresses GH in Type I and Type II epithelial cells (Beyea et al, 2005). The lungs were removed from the rats and frozen in liquid nitrogen.…”

“…An incision was made to expose the trachea; a slit was made on its ventral side, and a small catheter was inserted and tied to allow 4% paraformaldehyde to perfuse the tissue for 5 min at 20 cm H 2 O. Perfusions were made to a closed chest so the lungs would inflate to a natural state. After 5 min, the catheter was removed, the trachea was tied off, the rib cage was carefully opened, and the lungs removed, fixed with paraformaldehyde, and processed as in Beyea et al (2005). Slides were examined for GFP fluorescence.…”

“…Indeed, GH and GH mRNA are present in most mesenchymal and epithelial cells of the neonatal rat lung during the period of alveolarization (days 4 -14; Beyea et al, 2005). The possible functional importance of lung GH in lung function, therefore, has been further assessed in the present study, in which overexpression of GH in the neonatal lung during the alveolarization period has been induced by the administration of an aerosolized GHexpressing adenovirus (Adv).…”