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Depletion of bovine pituitary prolactin by cysteamine involves a thiol:disulfide mechanism

Journal Article · · Endocrinology; (United States)
OSTI ID:5777214
Cysteamine (2-aminoethanethiol (CySH)) reduces measurable PRL concentrations in vivo and in vitro. Since secretion is also inhibited, CySH may block conversion from a poorly assayable hormone storage form(s) to readily assayable, releasable PRL. This would represent a previously unrecognized mechanism for secretory regulation. We undertook the present study to identify the sites involved in the loss of measurable PRL (depletion) induced by cysteamine. The disulfide cystamine was ineffective on secretory granules unless combined with reduced glutathione, indicating the generation of the active CySH-thiol form. Pretreatment of granules with thiol-blocking agents resulted in dose-dependent enhancement of CySH inhibition, achieving nearly complete inhibition with 5 mM iodoacetamide. In contrast, pretreatment with reduced glutathione or dithiothreitol, respectively, impaired or abolished the CySH effect. These data suggest that the mechanism by which CySH causes PRL depletion is mediated by granule disulfides and the -SH of CySH. The regulation of thiol:disulfide equilibria appears to be an important determinant of the detectability of PRL storage forms and of their secretion.
Research Organization:
Univ. of Rochester School of Medicine and Dentistry, NY
OSTI ID:
5777214
Journal Information:
Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 115:4; ISSN ENDOA
Country of Publication:
United States
Language:
English