The biological activities of thyroid hormones are thought to be mediated by receptors generated by the TRα and TRβ loci. The existence of several receptor isoforms suggests that different functions are mediated by specific isoforms and raises the possibility of functional redundancies. We have inactivated both TRα and TRβ genes by homologous recombination in the mouse and compared the phenotypes of wild-type, and single and double mutant mice. We show by this method that the TRβ receptors are the most potent regulators of the production of thyroid stimulating hormone (TSH). However, in the absence of TRβ, the products of the TRα gene can fulfill this function as, in the absence of any receptors, TSH and thyroid hormone concentrations reach very high levels. We also show that TRβ, in contrast to TRα, is dispensable for the normal development of bone and intestine. In bone, the disruption of both TRα and TRβ genes does not modify the maturation delay observed in TRα -/-mice. In the ileum, the absence of any receptor results in a much more severe impairment than that observed in TRα -/-animals. We conclude that each of the two families of proteins mediate specific functions of triiodothyronin (T3), and that redundancy is only partial and concerns a limited number of functions.

The diverse functions of thyroid hormones are thought to be mediated by two nuclear receptors, T3Rα1 and T3Rβ, encoded by the genes T3Rα and T3Rβ respectively. The T3Rα gene also produces a non‐ligand‐binding protein T3Rα2. The in vivo functions of these receptors are still unclear. We describe here the homozygous inactivation of the T3Rα gene which abrogates the production of both T3Rα1 and T3Rα2 isoforms and that leads to death in mice within 5 weeks after birth. After 2 weeks of life, the homozygous mice become progressively hypothyroidic and exhibit a growth arrest. Small intestine and bones showed a strongly delayed maturation. In contrast to the negative regulatory function of the T3Rβ gene on thyroid hormone production, our data show that the T3Rα gene products are involved in up‐regulation of thyroid hormone production at weaning time. Thus, thyroid hormone production might be balanced through a positive T3Rα and a negative T3Rβ pathway. The abnormal phenotypes observed on the homozygous mutant mice strongly suggest that the T3Rα gene is essential for the transformation of a mother‐dependent pup to an ‘adult’ mouse. These data define crucial in vivo functions for thyroid hormones through a T3Rα pathway during post‐natal development.

Long-term treatment with glucocorticoids (GCs) leads to a rapid bone loss and to a greater risk of fractures. To evaluate the specific effects of this treatment on cancellous bone remodeling, structure, and microarchitecture, we compared 22 transiliac biopsy specimens taken in postmenopausal women (65 ؎ 6 years) receiving GCs (>7.5 mg/day, for at least 6 months) and 22 biopsy specimens taken in age-matched women with postmenopausal osteoporosis (PMOP), all untreated and having either at least one vertebral fracture or a T score < ؊2.5 SD. On these biopsy specimens, we measured static and dynamic parameters reflecting trabecular bone formation and resorption. Also, we performed the strut analysis and evaluated the trabecular bone pattern factor (