Thyroid hormones increase cystatin C levels in vivo. To study whether 3,3',5-triiodo-L-thyronine (T-3) stimulates the production of cystatin C in vitro, we used a T-3-responsive osteoblastic cell line (PyMS) which can be kept in serum-free culture. We compared the effects of T-3 on cystatin C mRNA expression (by Northern) and on protein release (by Western and ELISA) with those of dexamethasone (dex). Triiodothyronine increased cystatin C mRNA expression and cystatin C accumulation in culture media in a dose- and time-dependent manner, 1.5-fold at 1 nmol/l after 4 d; dex (100 nmol/l) was more potent and increased cystatin C accumulation 3-fold after 4 d. Triiodothyronine but not dex stimulated glucose uptake. Our in vitro findings explain in vivo observations. Triiodothyronine-induced increase in the production of cystatin C may be related to an increased cell metabolism and proteolysis control demand. (C) 2012 Elsevier Inc. All rights reserved.