RELAXIN - A PLEIOTROPIC HORMONE

1. Relaxin is a peptide hormone of about 6000 Da belonging to the insu lin family. Like insulin, relaxin is composed by two disulfide-linked chains, termed the A and B chains, the B chain bearing the receptor in teraction site. 2. Relaxin is produced primarily by the corpus luteum, in both pregnant and nonpregnant females. It attains the highest plas ma levels during pregnancy, In this condition, relaxin is also produce d by the decidua and placenta. In males, relaxin is synthesized in the prostate and released in the seminal fluid. An additional source of r elaxin has recently been identified in the heart atria. 3. Relaxin has a broad range of biologic activities, some of which have been known f or a long time. These latter ones include: (a) the induction of collag en remodeling and consequent softening of the tissues of the birth can al in view of delivery; (b) the inhibition of uterine contractile acti vity; (c) the stimulation of growth and differentiation of the mammary gland. 4. In more recent years, novel sites of relaxin action have be en recognized. In particular, it has been shown that relaxin: (a) regu lates growth and differentiation of breast cancer cells in culture; (b ) promotes dilation of blood vessels in several organs and tissues, in cluding the uterus, the mammary gland, the lung and the heart; (c) has a chronotropic action on the heart; (d) inhibits the release of hista mine by mast cells, thus being able to counteract experimental allergi c asthma; (d) depresses aggregation of platelets and their release by megakaryocytes; (e) influences the secretion of hormones by the pituit ary gland; and (f) contributes to the regulation of fluid balance. 5. Concerning the mechanisms of action of relaxin, stimulation of nitric oxide generation, with consequent rise in intracellular cyclic GMP lev els, and stimulation of cyclic AMP production have been demonstrated t o occur in the target cells and organs. 6. It may be expected that the next decade will provide answers about the utility of relaxin, in ter ms of insight into the actual physiologic functions of relaxin in the animal kingdom and especially in man, in view of possible therapeutic use of relaxin or relaxin-derived drugs in human disease, especially c onsidering that human recombinant relaxin is now available for clinica l experimentation. Copyright (C) 1997 Elsevier Science Inc.