STRUCTURE-FUNCTION RELATIONSHIP IN PARATHYROID HORMONE

Abstract

Parathyroid hormone (PTH) is the main regulator of calcium homeostasis and controls resorption as well as formation of bone. We assayed overlapping PTH fragments for their capability to stimulate either adenylate cyclase activity or DNA synthesis in in appropriate renal or skeletal cell systems. From these studies we concluded that PTH-induced enhancement of cellular cAMP levels and of cell proliferation are exerted by different functional domains of the hormone molecule. Their conincidence with structural domains will be discussed. After establishment of an efficient expression system for human PTH in E. coli both functional and structural considerations lead to a series of hormone variants. Their biological characterization showed that individual PTH effects could selectively be affected by these mutations. Therefore, site-directed mutagenesis conceivably opens up the possibility to select for either anabolic or catabolic in vivo activities of PTH. Functional design of a potent inducer-of bone growth might be of considerable clinical interest.