EXPRESSION OF ADRENOMEDULLIN AND ITS RECEPTOR DURING EMBRYOGENESIS SUGGESTS AUTOCRINE OR PARACRINE MODES OF ACTION

The present study reports the developmental patterns of expression of adrenomedullin (AM) in rat and mouse embryos. AM is a novel multifunct ional peptide recently isolated from a human pheochromocytoma, which h as been shown to promote growth in a variety of mammalian cell Lines. We have applied several techniques to investigate the localization of both tile AM peptide and its receptor throughout development. Immunocy tochemical detection has been performed using different specific antib odies against AM and its gene-related peptide pro-AM N-terminal 20 pep tide. In situ hybridization showed the localization of the messenger R NAs for AM and its receptor. Western blot analysis together with rever se transcription-PCR gave further support to the localization of AM an d ita receptor in a variety of embryonic tissues. The localization of the receptor paralleled that of AM itself, suggesting an autocrine or paracrine mode of action. The spatio-temporal pattern of expression of AM in cardiovascular, neural, Rad skeletal-forming tissues as well as in the main embryonic internal organs is described. The primitive pla centa, especially the giant trophoblastic dells, shows high levels of AM and AM receptor. The heart is the first organ that expresses AM dur ing development. Tho kidney, lung, and developing tooth, in which epit helial-mesenchymal interactions are taking place, show specific patter ns of AM expression. In several regions of the embryo, the patterns of AM expression correspond to the degree of differentiation. The possib le involvement of AM in the control of embryonic invasion, proliferati on and differentiation is discussed.