TY - JOUR
T1 - ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells
AU - Reichenstein, Moshe
AU - Reich, Reuven
AU - Lehoux, Jean Guy
AU - Hanukoglu, Israel
PY - 2004/2/27
Y1 - 2004/2/27
N2 - To identify genes that are induced by corticotropin (ACTH) in adrenal cortex cells, we carried out a differential hybridization screening of adrenal cortex cDNA libraries. Some of the clones we identified represented tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA. We examined ACTH dependence of the expression of TIMP-1 in vitro in cultured bovine adrenocortical cells, and in ACTH-treated rats. Northern blot analysis of total RNA from cells showed that the level of TIMP-1 mRNA increases sharply within 3h after ACTH stimulation. Since TIMP-1 inhibits some cell matrix metalloproteinases (MMPs) of the collagenase type, we examined the effect of ACTH on collagenase activity in bovine adrenocortical cells. Exposure of confluent cultures to ACTH for 24h showed dose-dependent inhibition of collagenase activity. Northern blot analysis of total RNA from rat adrenal zona fasciculata-reticularis and zona glomerulosa showed that in both of these zones TIMP-1 expression was induced within 12h after ACTH injection. Long-term (9 days) treatment with ACTH increased TIMP-1 mRNA levels nearly sixfold in zona fasciculata-reticularis. Overall, our results show that ACTH causes induction of TIMP-1 and suppression of collagenase activity, and suggest that ACTH may modulate the activities of MMPs and hence cell matrix remodeling.
AB - To identify genes that are induced by corticotropin (ACTH) in adrenal cortex cells, we carried out a differential hybridization screening of adrenal cortex cDNA libraries. Some of the clones we identified represented tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA. We examined ACTH dependence of the expression of TIMP-1 in vitro in cultured bovine adrenocortical cells, and in ACTH-treated rats. Northern blot analysis of total RNA from cells showed that the level of TIMP-1 mRNA increases sharply within 3h after ACTH stimulation. Since TIMP-1 inhibits some cell matrix metalloproteinases (MMPs) of the collagenase type, we examined the effect of ACTH on collagenase activity in bovine adrenocortical cells. Exposure of confluent cultures to ACTH for 24h showed dose-dependent inhibition of collagenase activity. Northern blot analysis of total RNA from rat adrenal zona fasciculata-reticularis and zona glomerulosa showed that in both of these zones TIMP-1 expression was induced within 12h after ACTH injection. Long-term (9 days) treatment with ACTH increased TIMP-1 mRNA levels nearly sixfold in zona fasciculata-reticularis. Overall, our results show that ACTH causes induction of TIMP-1 and suppression of collagenase activity, and suggest that ACTH may modulate the activities of MMPs and hence cell matrix remodeling.
KW - ACTH
KW - Bovine adrenocortical cells
KW - Collagenase regulation
KW - Rat adrenal cortex
KW - TIMP-1 mRNA
UR - http://www.scopus.com/inward/record.url?scp=1542407821&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2003.11.011
DO - 10.1016/j.mce.2003.11.011
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C2 - 15026182
AN - SCOPUS:1542407821
SN - 0303-7207
VL - 215
SP - 109
EP - 114
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -