Biosynthesis of polypeptide hormones

The biosynthesis of numerous polypeptide hormones implicates two types of precursors: pre- and prohormones. The structure, characteristics, and role of these hormone precursors is discussed taking as examples parathyroid hormone and insulin. After this general introduction, the case of the common precursor for adrenocorticotropin and beta-lipotropin is then discussed. Its maturation proceeds through a serie of proteolytic steps which lead to the formation of various end products characterized each by a biological activity of its own.     

Model-building of neurohypophyseal hormones

An attempt is made to construct models of the polypeptide backbone of the neurohypophyseal hormones. Using the sequences of six hormones and the empirical statistical approach (Kabat &; Wu, 1972; Wu &; Kabat, 1973), an initial selection is made of a set of φ, ψ angles satisfying all six sequences from a 20 × 20 × 20 table of φ, ψ values of tripeptides in 11 known proteins. Because of insufficient data at several positions, φ, ψ angles in the α-helical and β-sheet domains were considered as possible alternatives and the final selection was made to bring the disulfide bond as close as possible (model I). These initial values are then subjected to an energy minimization to refine the model; reasonable agreement with nuclear magnetic resonance data for possible φ values is obtained. Model II is constructed to be consistent with the available nuclear magnetic resonance data and the suggestion of a sequential Cu²⁺-binding site. Both models contain similar structural features and may be converted to one another with rotation of only a few angles. Interactive computer graphics was applied to construct model II, and its use in problems in this type is described. The relation of the experimental data to the various models that have been proposed for the neurohypophyseal hormones is discussed and an experiment is suggested that may permit a choice between them.     

Invertebrate neuropeptide hormones

The development of a long-term research program on the neurosecretory hormones of arthropods is described. The purification and full characterization of the first invertebrate neurohormones, the red pigment-concentrating hormone (RPCH) and the distal retinal pigment hormone (DRPH) demonstrated that they are peptides, an octapeptide and an octadecapeptide, respectively. Physiological function studies with the pure hormones and their synthetic preparations showed that the RPCH acts as a general pigment-concentrating hormone (PCH), and that the DRPH, in addition to its light-adaptive function, also constitutes a general pigment-dispersing hormone (PDH). In the regulation of the color-adaptation of the animals, the two hormones act as antagonists. The chromatophorotropic activities are widely distributed within the arthropod neuroendocrine systems. Purification of the pigment-concentrating activities from the locust corpora cardiaca lead to the isolation and characterization of the first insect neurohormones, the adipokinetic hormones (AKH I and AKH II). These two hormones, AKH I being a decapeptide and AKH II being an octapeptide, are close structural analogs to the crustacean PCH, demonstrating a common evolution of arthropod neurohormones. The hormones of this PCH-family all cross-react, but structure-function studies of the hormones show that quite different parts of their structure are involved in their binding to the various receptors.