FETAL PULMONARY IMMUNOREACTIVE ADRENOCORTICOTROPIN - MOLECULAR-WEIGHTAND CELLULAR-LOCALIZATION

The hypothalamus-pituitary-adrenal axis of the sheep fetus plays a cri tical role in fetal development, responsiveness to stress, and initiat ion of parturition. We have recently reported that the fetal lung cont ains and secretes significant amounts of immunoreactive adrenocorticot ropin (iACTH). The present study was designed to identify the molecula r weight profile and the cellular location of iACTH in this tissue. iA CTH extracted from fetal lung was immunoprecipitated, electrophoresed, and immunoblotted, Pulmonary iACTH was found in several molecular for ms. The largest peptides appeared as doublets, and had molecular weigh ts similar to POMC (32, 33 kD). Smaller peptides appeared in molecular weights (17, 24, and 27 kD) which were not consistent with the post-t ranslational processing of POMC in fetal pituitary, but which were con sistent with known processing of POMC by chromaffin granule aspartyl p rotease. None of the molecular forms of iACTH were glycosylated. Immun ohistochemistry revealed that the iACTH was contained within bronchial epithelium and within groups of cells within the parenchyma of the lu ng. Both of these types of cells are consistent with pulmonary neuroen docrine cells. The distribution of neuroendocrine cells and apparent c oncordance with the iACTH-positive cells was confirmed by immunostaini ng for neuron specific enolase, a marker for neuroendocrine cells with in the lung. We conclude that the lung contains unprocessed and partia lly processed POMC within cells known to contain neuropeptides. We spe culate that secretion of the POMC-related peptides from these cells is physiologically important in the late-gestation fetus. (C) 1998 Elsev ier Science B.V.