Expression of growth hormone and its receptor in the lungs of embryonic chicks

Abstract

The lung is well established as being a postnatal target site for growth hormone (GH) action, since pathophysiological states of GH excess and deficiency are both associated with impaired pulmonary function. Pituitary GH is therefore probably involved in normal lung growth or development, although perinatal lung development occurs prior to the differentiation of pituitary somatotrophs and the ontogeny of pituitary GH secretion. The lung itself may, however, be a site of GH production during prenatal development, since a specific GH-response gene (a marker of GH activity) is expressed in the lungs of early chick embryos, in which GH immunoreactivity is widespread in many other peripheral tissues. We have assessed this possibility in embryonic chicks. A 690-bp cDNA, identical in size and nucleotide sequence to the full-length pituitary GH transcript, was amplified by reverse transcription/polymerase chain reaction from total RNA extracted from the lungs of embryos at 11, 13, 15, and 18 days of the 21-day incubation period. This transcript was localized by in situ hybridization to mesenchymal and epithelial cells of the developing lungs, in which specific GH immunoreactivity was similarly located. Intense GH immunoreactivity was also present after embryonic day 15 (ED15) in the smooth muscle surrounding blood vessels in the lung and surrounding the bronchioles. Lung GH immunoreactivity was primarily associated with a 15-kDa protein, rather than the 26-kDa protein in the pituitary gland. After the onset of pituitary GH secretion (at ED17), GH mRNA was barely detectable in the lungs of ED20 embryos, at the start of lung breathing. GH immunoreactivity was, however, still present in some cells in the lungs of ED20 embryos. GH-receptor mRNA and immunoreactivity were also widespread and abundant within the embryonic lung. Lung GH may thus have autocrine or paracrine roles in lung development or in pulmonary function prior to the ontogeny of the pituitary gland and the appearance of GH in peripheral plasma.

Extrapituitary growth hormone

“…Rat lymphocytes, for instance, produce a GH cDNA that is identical to pituitary GH cDNA in its nucleotide sequence and codes for the same protein [288,289], which is released from lymphocytes in vitro [286]. This possibility is also supported by the demonstration that GH mRNA, identical to that in the pituitary gland, is, for instance, present in hypothalamic and extra-hypothalamic regions of the chicken brain [290], in the chick neural retina [35], in chicken immune tissues [77,78,291], in the chicken testis [164], and in the chicken lung [217]. In summary, it is now well established that authentic GH moieties are present in many extrapituitary tissues in which they are produced.…”

“…This possibility is supported by the discovery of GH mRNA, identical in nucleotide sequence to pituitary mRNA, in the lungs of embryonic chicks [217]. In situ hybridization localized this transcript to mesenchymal and epithelial cells of developing lungs, in which specific GH immunoreactivity is similarly located.…”

“…Growth hormone mRNA has also been found by in situ hybridization in endothelial cells and the surrounding smooth muscle cells of veins and arteries in the liver, spleen, and thymus of rats [65], embryonic chick lungs [217], and human immune tissues [72], in which the autocrine production of GH may be involved in tissue angiogenesis. GH mRNA has similarly been found in skeletal muscles of chick embryos [14], with a distribution similar to that of the GHR [20].…”

DNA microarray profiling identified a new role of growth hormone in vascular remodeling of rat ductus arteriosus

“…A growing body of evidence, however, has revealed the importance of GH in tissue differentiation during fetal development. First, many fetal tissues, including vascular endothelium and smooth muscle, express GHR [14,15]. Therefore, GH likely activates an intracellular signal pathway through GHR in fetuses.…”

Pathophysiology and Prevention of Bronchopulmonary Dysplasia

“…Knockout mice deficient in corticotrophin releasing hormone demonstrate early failure of development of the air spaces and their newborn offspring all die of respiratory failure [5]. Other hormonal influences are also important regulators of normal lung differentiation and alveolarisation such as thyroid hormone [6], growth hormone [7], oestrogen and progesterone [8], parathyroid hormone related peptide [9] and bombesin like peptide [10]. These growth factors are thought to be expressed and regulated by physical force such as lung stretching [11], explaining the importance of fetal breathing movements for normal lung growth.…”