Osmotic pressure regulation of prolactin and growth hormone release from XXXX secretory granules.

@entity1433 @entity2041 @entity2197 @entity9592 @entity969 @entity1432 @entity1520 @entity291 @entity6743
PRL and GH are stored in @entity291 pituitary secretory granules in part as intermolecular @entity1520 -linked multimers (as many as 50 monomers/oligomer). In vitro incubation of granules with reduced @entity2041 ( @entity2197 ) results in the production of monomeric hormones and increased hormone release. We tested the hypothesis that increases in intragranular osmolality due to conversion of oligomers to lower mol wt forms are key to granule rupture. Hormone release was measured after granule incubations in medium made hyperosmotic by the addition of @entity9592 or @entity969 . PRL release at pH 7.8 with 0.7 M @entity9592 was reduced to 43.5% of the control value, whereas GH release ranged from 70-100% of the control value. Augmented release stimulated by 2 mM @entity2197 was also diminished by @entity9592 , to 17.9% (PRL) and 75.6% (GH) of control values. The IC50 for @entity9592 inhibition of PRL release was 0.62 M; this shifted to 0.38 M in the presence of 2 mM @entity2197 . @entity9592 also blunted the granule response to @entity2197 at all other @entity2197 concentrations tested and decreased stimulated release at pH 9 as well as at 7.8. Interference with the ability to maintain an osmotic gradient, a maneuver accomplished by partial disruption of granule membranes with 0.5% @entity6743 treatment, reduced or abolished the @entity9592 inhibition. Molecular sizing of granule fractions on Superose-6 (Pharmacia) indicated that PRL monomers remaining in the pelletable granule fraction increased with @entity9592 about 2-fold under both basal and @entity2197 -stimulated conditions. These data support the concept that @entity1432 :disulfide equilibria may be important in PRL and GH storage and secretion by their influence on intragranular osmolality. In exocytosis in vivo, osmotically mediated granule rupture may be triggered by @entity1433 during granule:plasma membrane fusion.
