Endocrine Abstracts

Background: Thyroid hormones increase both serum levels of cystatin C and renal glomerular filtration rate (reflected by lower serum creatinine); the latter is considered the main determinant of cystatin C levels. A potential explanation for this apparently discrepant finding is an increased production, rather than a decreased clearance, of cystatin C. To study whether 3,3′,5-triiodo-L-thyronine (T₃) increases the production of cystatin C in a well defined in vitro system.

Methods: Rat bone-derived osteoblastic (PyMS) cells were kept in long term serum-free culture and treated for different time periods and at different concentrations with T₃, and cystatin C mRNA was assessed by Northern analysis and cystatin C protein in the medium of the cells by western analysis and by ELISA. [1-¹⁴C]-2-deoxy-D-glucose (2DG) uptake was also measured.

Results: T₃ increased 2DG uptake by the cells as well as cystatin C mRNA expression and cystatin C accumulation in culture media, in a dose (0.01 to 1 nM)- and time (more markedly after 4 days than after 1 day)-dependent manner, up to 2.5-fold (2DG uptake), 2.8-fold (cystatin C mRNA) and 1.5-fold (cystatin C release) at 1 nM after 4 days. Dexamethasone (100 nM) also increased cystatin C production but decreased 2DG uptake whereas 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃, 1 nM) also increased 2 DG uptake but decreased cystatin C production. T₃ did not stimulate cell replication.

Conclusions: T₃ stimulates glucose uptake and the production of cystatin C; the findings may be related to an increased metabolism and energy as well as proteolysis control demand induced by thyroid hormones and help to explain (via spillover of locally increased cystatin C at multiple sites into the circulation) the dependency of cystatin C serum levels of T₃ in vivo.