Preface

 

    The seminal observation by Liggins in 1969 that glucocorticoid treatment of fetallambs resulted in enhanced lung maturation initiated the concept that the fetal lung is ahormonally responsive organ. During the past thirty years, great progress has been madein defining the roles of steroid, peptide, and polypeptide hormones in lung branchingmorphogenesis, differentiation of specialized cell types, and surfactant synthesis. Inaddition to glucocorticoids, it is apparent that the sex steroids, retinoids, catecholamines,prostaglandins, and peptide and polypeptide hormones, including a number of growthfactors and cytokines, influence lung growth and differentiation as well as surfactantsynthesis. Whereas the steroids and certain polypeptide hormones are delivered to lungthrough the systemic circulation, growth factors are produced locally by mesenchymalcells surrounding the developing lung buds, by type II epithelial cells, or by their precursors.Additionally, a variety of bioactive peptides are produced by innervated clusters ofneuroendocrine cells that lie within the primitive airway epithelium.

 

    Endocrinology of the Lung: Development and Surfactant Synthesis contains contributionsfrom investigators studying the actions of the various classes of endocrine, paracrine,and neuroendocrine factors on lung development and surfactant synthesis. The modelsystems used in their studies range from whole animals to organ and cell culture and totransgenic, genetically altered, and gene-targeted mice. The first seven chapters aredevoted to the actions of glucocorticoids on lung development and on the synthesis ofsurfactant glycerophospholipids and the surfactant proteins—SP-A, SP-B, and SP-C.Included in this group is a chapter on the role of the major histocompatibility complex(MHC) locus in glucocorticoid responsiveness, as well as one that addresses the role ofcorticotropin-releasing hormone (CRH) and glucocorticoids in lung development andsurfactant synthesis using CRH gene-targeted mice. Two chapters address the actions ofhormones that bind to other members of the nuclear receptor family; one is concernedwith mechanisms that underlie the sexual dimorphism of fetal lung maturation and sexdifferences in responsiveness to perinatal glucocorticoid administration, while the otheris concerned with the roles of retinoids and their receptors in lung development, surfactantsynthesis, and the repair of lung injury in human premature newborns. Anotherchapter deals with fetal lung maturation and surfactant synthesis in the diabetic pregnancyand the effects of insulin on the synthesis of surfactant lipids and proteins. Theremaining six chapters review the importance of cell–cell interactions and elaborate onvarious growth factors and bioactive peptides in lung branching morphogenesis, celldifferentiation, gene expression, and pulmonary pathophysiology. The use of transgenicand gene-targeted mice to define the roles of members of a number of growth-factorfamilies and their receptors in the regulation of lung morphogenesis and cellular differentiationalso is addressed.

 

    It is therefore apparent that lung growth, differentiation, and surfactant production arecontrolled by a variety of circulating and locally produced hormones and growth factorsthat exert their effects via endocrine, paracrine, autocrine, neuroendocrine, and possiblyintracrine mechanisms. In light of the importance of circulating hormones and of growthfactor-mediated cellular interactions in lung growth, cell differentiation, function, andpathophysiology, it is my hope that Endocrinology of the Lung: Development and SurfactantSynthesis will have appeal, not only to pulmonary biologists, but also to thoseworking in the areas of hormone action, and developmental and cell biology of otherorgan systems.

 

    I would like to express my sincere appreciation to the contributors who have collaboratedto make this a comprehensive review of the lung as an endocrine-responsive organ.

 

                                                                                                                                                                                                                                                                                    Carole R. Mendelson