Progress in chronophysiology of peptide hormones with emphasis on clinical application of analogues

It is now established that peptide hormones are among the most versatile substances involved in intercellular communications. By substitution of one or more natural aminoacids, numerous peptide analogues have been synthesized with increased duration of action and potency with respect to endogenous hormones. Most of these effects are programmable as a function of dose and timing of administration. Not surprisingly, the chronobiological use of hormone-related peptides may represent a valuable tool providing new approaches to diagnosis and therapy of different disease states. One pertinent example of the applicability of peptide analogues refers to a new short chain ACTH analogue (ACTH 1-17; Synchrodyn) that has been proved useful to reset or preset the rhythmic ordering of a number of functions and to provide, furthermore, information about specific pathogenetic mechanisms and/or subtle alterations of the adrenal function. A large body of evidence indicates that the same concepts apply to most actions of the gonadotropin-releasing hormone (LH-RH) related analogues. The efficacy of the so-called low-dose pulsatile LH-RH therapy in the management of hypogonadotropic hypogonadism and of some forms of infertility seems now established. The use of potent analogues is providing new approaches to the heretofore unsuccessful therapies in a number of disease conditions. In this light, chronoendocrinology and biotechnology have to be mutually supporting. Novel clinical applications are expected from the emerging use of portable instrumentation designed to record endogenous data and/or to deliver drugs according to a temporal program.