Type 2 Iodothyronine Selenodeiodinase Is Expressed throughout the Mouse Skeleton and in the MC3T3-E1 Mouse Osteoblastic Cell Line during Differentiation

Abstract

Thyroid hormone affects multiple aspects of bone metabolism, but little is known about thyroid hormone deiodination in bone cells except that cultures of skeletal cells and bone organ express types 1 and 2 iodothyronine deiodinases (D1 and D2) mRNAs. In the present study, outer ring deiodination (ORD) activity was detected in bone extracts of multiple sites of the mouse skeleton, bone marrow, and the MC3T3-E1 osteoblastic cell line. In all tissues, ORD was detected using 125I-rT3 or 125I-T4 as substrates and was found to be 6-n-propylthiouracil insensitive, display a Michaelis constant (T4) of approximately 1 nM, increase about 3-fold in hypo- and virtually disappear in thyrotoxicosis. Extracts of calvaria had the lowest ORD activity, whereas tibial and femoral extracts had roughly three times as much. The absence of ORD activity in bone extracts from mice with targeted disruption of the Dio2 gene confirms the principal role of D2 in this tissue. In the MC3T3-E1 osteoblasts, D2 activity increased in a time-dependent manner after plating, and with the content of selenium in the media, reaching a maximum 5-7 d later as cells attained more than 90% confluence. In these cells D2 half-life is about 30-40 min, which is further accelerated by exposure to substrate and stabilized by the proteasome inhibitor, MG132. Treatment with vitamin D [1,25(OH)2VD]-induced D2 activity by 2- to 3-fold as early as 24 h, regardless of the level of cell confluence, but estradiol, PTH, forskolin, leptin, TNFalpha, TGFbeta, and dexamethasone did not affect D2. Given the role of D2 in other cell types and processes, it is likely that bone ORD not only plays a role in bone development and adult bone T3 homeostasis but also contributes to extrathyroidal T3 production and maintenance of serum T3.

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…Estimates suggest that at least half of the T 3 present in D2-expressing tissues is produced locally from deiodination of T 4 (86)(87)(88)(89). More recently D2 expression has been found in a large number of tissues and cells (90)(91)(92)(93)(94)(95)(96)(97)(98), illustrating the importance of defining its contribution to tissue-specific thyroid hormone signaling. The determination of the sources of intracellular T 3 is feasible because plasma T 3 equilibrates rapidly with most tissues (but not all).…”

The effects of sex-steroid administration on the pituitary–thyroid axis in transsexuals

“…Low-dose estrogens did not affect hepatic D1 activity, whereas testosterone increased D1 activity. Currently, there is no evidence to support an effect of androgens or estrogens on D2 activity, but the data are limited to D2 activity in the rat pituitary (6) and the mouse bone (21). Whether testosterone increased T 4 to T 3 conversion by effects on D1 or D2 remains speculative.…”

Type 2 iodothyronine deiodinase is highly expressed in medullary thyroid carcinoma

“…In contrast, DEX was reported to decrease D2 activity in cultured mouse neuroblastoma cells (St Germain, 1986). In the MC3T3-E1 osteoblastic cell line, DEX treatment has no effect on D2 expression (Gouveia et al, 2005). Therefore, the effect of glucocorticoids on D2 expression seems to differ among the various neoplastic tissues.…”