Pancreastatin secretion by pituitary adenomas and regulation of chromogranin B mRNA expression.
Pancreastatin, a carboxyl-terminal amidated peptide derived from chromogranin (Cg)A, inhibits secretion of insulin and parathyroid hormone. Our recent studies found significant amounts of immunoreactive pancreastatin in all pituitary adenomas except prolactin adenomas. To analyze the effects of pancreastatin on pituitary cell function, 17 cultured pituitary adenomas were examined for immunoreactive pancreastatin and pancreastatin secretion by the tumors. The effects of pancreastatin on pituitary hormone secretion and on pituitary hormone (follicle-stimulating hormone and prolactin), CgA, and CgB mRNA levels were also examined. Immunoreactive pancreastatin and CgA were present diffusely in gonadotroph and null cell adenomas, but only a few prolactin adenoma cells expressed pancreastatin or CgA. When cells were treated with hypothalamic peptides, gonadotroph adenomas were the only group that released increased amounts of pancreastatin in response to gonadotropin-releasing hormone (10(-7) mol/L). Pancreastatin (10(-7) mol/L) treatment did not stimulate pituitary hormone secretion significantly. In situ hybridization analyses showed that gonadotropin-releasing hormone and pancreastatin treatment led to significant increases in CgB and follicle-stimulating hormone mRNAs in gonadotroph adenomas, whereas CgA mRNA levels did not change significantly. These results show that there is a differential distribution of pancreastatin secretion in pituitary adenomas and that the hypothalamic hormone gonadotropin-releasing hormone and the CgA-derived peptide pancreastatin can regulate CgB mRNA in gonadotroph adenomas, suggesting an autocrine effect of pancreastatin on pituitary tumor function.
Jin
L
L
Department of Laboratory Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Scheithauer
B W
BW
Young
W F
WF
Davis
D H
DH
Klee
G G
GG
Lloyd
R V
RV
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D002648:Child; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007028:Hypothalamic Hormones / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010187:Pancreatic Hormones / Q000378:metabolism*; D010907:Pituitary Hormones / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D015175:Prolactinoma / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
C506134:CHGB protein, human; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins; D007028:Hypothalamic Hormones; D010187:Pancreatic Hormones; D010907:Pituitary Hormones; D012333:RNA, Messenger; C050836:pancreastatin