Glucose-regulated protein-78 expression in the rat adrenal cortex.
We have postulated that steroidogenesis activator polypeptide (SAP) is a product of glucose-regulated protein-78 (grp78) proteolysis on the basis of a number of considerations, including a striking sequence similarity between the carboxyl-terminal region of grp78 and SAP. Since ACTH stimulates the rapid intracellular accumulation of SAP, experiments were conducted to determine whether ACTH might also regulate levels of grp78 mRNA and/or protein. Using a grp78 cDNA probe, Northern analysis of total RNA isolated from hypophysectomized or dexamethasone-suppressed rats revealed that neither treatment had a measurable influence on steady-state levels of grp78 mRNA over a 4-day period. Moreover, immunoblotting with an antiserum directed against a shared grp78/SAP sequence failed to detect a significant change in the grp78 content of adrenal homogenates from dexamethasone-suppressed rats as compared with untreated controls. On the other hand, grp78 in cultured rat adrenocortical cells fell to 50% of that in time-zero controls after 72 h in the absence of ACTH, whereas inclusion of ACTH in the medium blocked this decline. We conclude that while adrenocortical grp78 may be under some measure of trophic ACTH control, the rapid fluctuations reported for SAP are not likely to be driven by large changes in the size of the grp78 pool.
Department of Biochemistry, School of Medicine, State University of New York, Buffalo 14214.
J
J
Gregoire
L M
LM
Mertz
R C
RC
Pedersen
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D015870:Gene Expression; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C051684:GRP78 protein, rat; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone