Atrial Natriuretic Peptide Prohormone Gene Expression: Hormones and Diseases That Upregulate its Expression

Atrial natriuretic peptides consist of a family of peptide hormones that are synthesized by three separate genes and then stored as three different prohormones (i.e., 126-amino acid [a.a.]) atrial natriuretic peptide (ANP), 108-a.a. brain natriuretic peptide (BNP), and 126-aa. C-natriuretic peptide (CNP) prohormones. The gene encoding for the synthesis of the atrial natriuretic peptide prohormone (proANP) consists of three exons and two introns. Exon 1 encodes the signal peptide and the first 16 aa. of the ANP prohormone. These 16 a.a. form the N-terminus of a peptide hormone named long-acting natriuretic hormone (LANH). A valine-to-methionine substitution in LANH results in a 2-fold increased incidence of strokes in humans. Exon 2 of the proANP gene encodes for three peptide hormones, i.e., vessel dilator, kaliuretic hormone, and ANP. Each of the proANP gene products have vasodilatory, diuretic, natriuretic, and/or kaliuretic properties. Stretch, glucocorticoids, thyroid hormone(s), mineralocorticoids, and calcium enhance proANP gene expression. Enhanced proANP gene expression is found in congestive heart failure, hypertension, and cirrhosis with ascites. The proANP gene is present with invertebrates and plants as well as in humans and other vertebrates.