Thrombospondin-1 is a glucocorticoid responsive protein in humans

Johanna Barclay, Carolyn Petersons, Sahar Keshvari, Jane Sorbello, Campbell Thompson, Johannes Prins, Morton Burt, Johathan Whitehead, Warrick Inder

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    Objective: Thrombospondin-1 (TSP1) is a matricellular protein whose gene expression has previously been shown to increase acutely after exposure to dexamethasone in vitro. The aim of this study was to determine if TSP1 is altered by acute and chronic states of glucocorticoid excess in human subjects. Design and methods: Three studies have been undertaken to assess the difference or change in TSP1 in response to altered glucocorticoid activity: i) an acute interventional study assessed the effects of a single 4 mg dose of dexamethasone in 20 healthy volunteers; ii) a cross-sectional study compared plasma TSP1 in 20 healthy volunteers and eight patients with Cushing's syndrome; iii) an interventional study assessed the effect on plasma TSP1 of an increase in hydrocortisone dose from %20 mg/day to 30 mg/day for 7 days in 16 patients with secondary adrenal insufficiency. Results: In healthy volunteers, 4 mg dexamethasone significantly increased peripheral blood mononuclear cell (PBMC) TSP1 mRNA levels (P<0.0001) and plasma TSP1 concentrations (P<0.0001), peaking at 12 h. Median (interquartile range) plasma TSP1 was higher in Cushing's, 638 (535-756) ng/ml, than in healthy volunteers, 272 (237-336) ng/ml (P<0.0001). Plasma TSP1 O400 ng/ml diagnosed Cushing's syndrome with sensitivity of 100% and specificity of 85%. The higher hydrocortisone dose increased plasma TSP1 from 139 (86-199) to 256 (133-516) ng/ml, (P<0.01) in patients with secondary adrenal insufficiency. Conclusions: TSP1 is a glucocorticoid responsive protein in humans. Further research is required to determine if plasma TSP1 has a role as a glucocorticoid biomarker.

    Original languageEnglish
    Pages (from-to)193-201
    Number of pages9
    JournalEuropean Journal of Endocrinology
    Volume174
    Issue number2
    DOIs
    Publication statusPublished - 2016

    Fingerprint Dive into the research topics of 'Thrombospondin-1 is a glucocorticoid responsive protein in humans'. Together they form a unique fingerprint.

  • Cite this

    Barclay, J., Petersons, C., Keshvari, S., Sorbello, J., Thompson, C., Prins, J., Burt, M., Whitehead, J., & Inder, W. (2016). Thrombospondin-1 is a glucocorticoid responsive protein in humans. European Journal of Endocrinology, 174(2), 193-201. https://doi.org/10.1530/EJE-15-0964