Effect of Thyroid Hormone and Growth Hormone on Recovery from Hypothyroidism of Epiphyseal Growth Plate Cartilage and Its Adjacent Bone

Abstract

Hypothyroidism was induced in young female Sprague-Dawley rats by the addition of methimazole (0.67 mg/ml) to drinking water for a period of 7 weeks (7-14 weeks of age). The responses of the articular cartilage, epiphyseal growth plate cartilage, epiphyseal trabecular bone, and metaphyseal trabecular bone in the proximal tibia were assessed by structural parameters. In addition, replacement therapies were introduced for the last 2 weeks of the experimental period. These included 0.7 U/kg BW human GH (hGH), 15 micrograms/kg BW L-T4 (T4), and a combination of hGH and T4 at the same doses. In the hypothyroid rats, the width of epiphyseal growth plate cartilage decreased by 27%, that of articular cartilage by 35%, epiphyseal trabecular bone volume by 30%, and metaphyseal trabecular bone volume by 66% relative to those in age-matched control tissues. T4 treatment led to a full restoration of the epiphyseal trabecular bone and surpassed by 40% the control value. The magnitude of the articular cartilage and the epiphyseal trabecular bone volume returned to control values, while that of metaphyseal trabecular bone was 68% of control values. Treatment with hGH did not improve the epiphyseal growth plate cartilage or articular cartilage. It did restore epiphyseal trabecular bone to almost normal values, but metaphyseal trabecular bone improved to only a small though significant level (45% of control value). The combination of T4 and hGH resulted in an additional enlargement in the width of the epiphyseal growth plate cartilage and an increase in metaphyseal trabecular bone volume compared to those in the T4 group. Qualitative examinations indicated that it was only in the T4 and T4 plus hGH groups that the lowest chondrocytes in the epiphyseal growth plate cartilage resumed their normal hypertrophied size. These results suggest that the change in the hypothyroid state do not rely solely on the lack of pituitary GH synthesis and secretion, as replacement by exogenous GH did not restore normal epiphyseal growth plate cartilage morphology or its remodeling into metaphyseal trabecular bone. Treatment with T4 (which restored endogenous pituitary GH to 30% of control levels) results in full recovery of the epiphyseal growth plate cartilage morphology along with its associated metaphyseal trabecular bone. In addition, it can also be concluded that the decrease in epiphyseal trabecular bone volume observed in the hypothyroid animals was due solely to the GH-deficient state that accompanied hypothyroidism.

Thyroid hormone actions on cartilage and bone: interactions with other hormones at the epiphyseal plate and effects on linear growth

“…Similar effects are also seen in articular cartilage, although GH does not enhance the actions of T 4 . The important findings from this study (Lewinson et al 1989) confirm the direct actions of thyroid hormone on the growth plate and exclude the possibility that thyroid responses are mediated via increased GH secretion.…”

“…Thyroid hormone effects on growth plate architecture Lewinson et al (1989) studied the effects of hypothyroidism and interactions between T 3 and GH on rat tibial growth plate morphology. In hypothyroid rats, the width of the epiphyseal plate is reduced as a consequence of the presence of fewer proliferative cells and a reduction in size of hypertrophic cells compared with controls.…”

O efeito molecular e estrutural do hormônio tiroideano no esqueleto

“…Entretanto, há evidências de que o hormônio tiroideano é capaz de atuar diretamente nos condróci-tos das placas de crescimento através de mecanismos independentes do GH. Foi mostrado, por exemplo, que, em ratos hipotiróideos, o GH sozinho não é capaz de induzir a organização dos condrócitos da placa de crescimento e promover a diferenciação de condrócitos proliferativos em hipertróficos (81,82). Recentemente, Robson e cols.…”

The effects of hypothyroidism on the proximal femoral physis in miniature swine

“…Decreases in physeal height or thickness of growth plate cartilage proliferating and hypertrophic zones are reported in hypothyroid rat models, 7 and diminished numbers of hypertrophic chondrocytes and disruption of endochondral bone formation have been identified in hypothyroidism. 8,9 Thyroid hormone has been linked to regulation of type X collagen synthesis, physeal chondrocyte hypertrophy, and terminal chondrocyte differentiation.…”

“…7,23,24 Miniature swine proximal femoral anatomy closely resembles that of human proximal femoral anatomy, [25][26][27] but to date this model has not been established in studying hypothyroid growth plate changes.…”