ACTH induces TIMP-1 expression and inhibits collagenase in adrenal cortex cells

Abstract

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 3 h 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 24 h 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 12 h 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.

Signaling Proteins Are Represented in Tissue Fluid/Lymph from Soft Tissues of Normal Human Legs at Concentrations Different from Serum

“…It suppresses the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodeling of the extracellular matrix. 33,34 In our studies, the normal L/S ratio was 2.5 and that of TIMP2 3.5.…”

Gender-dependent physiological implications of combined PAI-1 and TIMP-1 gene deficiency characterized in a mouse model

“…Collectively, these observations indicate a direct physiological link between ACTH and glucocorticoid hormones and the expression of PAI-1 and TIMP-1 in the adrenal glands during steady state. However, in response to different pathological conditions such as metabolic disorders and inflammation, ACTH and glucocorticoid hormones may also be involved in regulation of PAI-1 and TIMP-1 transcription in more distant organs (14, 35,37). Furthermore, the high levels of PAI-1 expression in uterus and ovaries and of TIMP-1 in ovaries magnify the importance of PAI-1 and TIMP-1 in ovulation, endometrial remodeling, and implantation (24,37).…”

Liposomal glucocorticoids as tumor-targeted anti-angiogenic nanomedicine in B16 melanoma-bearing mice

“…Once in the nucleus, GC/cGCR complexes modulate transcriptional responses of the majority of inflammatory, angiogenic, immunomodulatory and apoptotic genes, by binding directly to DNA, or by binding to proteins, e.g. to transcription factors involved in regulation of these genes [6][7][8][9][10][11][12]. GC can also interact at the posttranscriptional and translational level leading to suppression of a broad variety of factors responsible for angiogenesis, inflammation, apoptosis, and immune function [10].…”