Thrombospondin-1 is a glucocorticoid responsive protein in humans

Barclay, Johanna L., Petersons, Carolyn J., Keshvari, Sahar, Sorbello, Jane, Mangelsdorf, Brenda L., Thompson, Campbell H., Prins, Johannes B., Burt, Morton G., Whitehead, Jonathan P. and Inder, Warrick J. (2016) Thrombospondin-1 is a glucocorticoid responsive protein in humans. European Journal of Endocrinology, 174 2: 193-201. doi:10.1530/EJE-15-0964

Author Barclay, Johanna L.
Petersons, Carolyn J.
Keshvari, Sahar
Sorbello, Jane
Mangelsdorf, Brenda L.
Thompson, Campbell H.
Prins, Johannes B.
Burt, Morton G.
Whitehead, Jonathan P.
Inder, Warrick J.
Title Thrombospondin-1 is a glucocorticoid responsive protein in humans
Journal name European Journal of Endocrinology   Check publisher's open access policy
ISSN 1479-683X
Publication date 2016-02-01
Year available 2015
Sub-type Article (original research)
DOI 10.1530/EJE-15-0964
Open Access Status Not Open Access
Volume 174
Issue 2
Start page 193
End page 201
Total pages 9
Place of publication Woodlands, Bristol, United Kingdom
Publisher BioScientifica
Collection year 2016
Language eng
Formatted 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 >400 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2016 Collection
School of Medicine Publications
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