title: Prolactin and growth hormone aggregates in secretory granules: the need to understand the structure of the aggregate.
abstract: Prolactin and GH form reversible aggregates in the trans-Golgi lumen that become the dense cores of secretory granules. Aggregation is an economical means of sorting, because self-association removes the hormones from other possible pathways. Secretory granules containing different aggregates show different behavior, such as the reduction in stimulated release of granules containing R183H-GH compared with release of those containing wild-type hormone. Aggregates may facilitate localization of membrane proteins necessary for transport and exocytosis of secretory granules, and therefore understanding their properties is important. Three types of self-association have been characterized: dimers of human GH that form with Zn(2+), low-affinity self-association of human prolactin caused by acidic pH and Zn(2+) with macromolecular crowding, and amyloid fibers of prolactin. The best candidate for the form in most granules may be low-affinity self-association because it occurs rapidly at Zn(2+) concentrations that are likely to be in granules and reverses rapidly in neutral pH. Amyloid may form in older granules. Determining differences between aggregates of wild type and those of R183H-GH should help to understand why granules containing the mutant behave differently from those containing wild-type hormone. If reversible aggregation of other hormones, including those that are proteolytically processed, is the crucial act in forming granules, rather than use of a sorting signal, then prohormones should form reversible aggregates in solution in conditions that resemble those of the trans-Golgi lumen, including macromolecular crowding.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA. priscilla.dannies@yale.edu
authors.forename: Priscilla S
authors.initials: PS
authors.lastname: Dannies
mesh_terms: D000818:Animals; D001692:Biological Transport; D005089:Exocytosis; D006056:Golgi Apparatus / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011388:Prolactin / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D019382:Human Growth Hormone; D011388:Prolactin