ACTH secretion by mouse corticotroph AtT20 cells is negatively modulated by the intracellular level of 7B2.
7B2 is a pan-neuroendocrine protein known to facilitate the trafficking and activation of the prohormone proprotein convertase-2 (PC2). 7B2-null mice not only lack PC2 activity, but they also develop an adrenocorticotropic hormone (ACTH) hypersecretion syndrome, suggesting that 7B2 may regulate hormone secretion. To verify this possibility, we introduced into mouse corticotroph AtT20 cells a retroviral vector carrying either a sense or an antisense 7B2 transgene to induce higher and lower 7B2 expression, respectively. Relative to control AtT20 cells, 7B2-overexpressing cells released less ACTH following KCl-induced membrane depolarization, whereas cells expressing lower levels of 7B2 released relatively more, suggesting that 7B2-related peptides modulate regulated secretion in neuroendocrine cells.
Bergeron
François
F
Diseases of Aging Program, Ottawa Health Research Institute, University of Ottawa, 725 Parkdale Avenue, K1Y 4K9, Ottawa, ON, Canada.
Sirois
Francine
F
Mbikay
Majambu
M
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D005089:Exocytosis; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051859:Neuroendocrine Secretory Protein 7B2; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; D011994:Recombinant Proteins; D000324:Adrenocorticotropic Hormone