Thyroid hormone, but not parathyroid hormone, partially restores glucocorticoid-induced growth retardation.

Growth retardation is a serious side effect of long-term glucocorticoid (GC) treatment. In order to prevent or diminish this deleterious effect, a combination therapy including growth hormone (GH), a stimulator of bone growth, is often recommended. Parathyroid hormone (PTH) and thyroid hormone (T(4)) are important hormonal regulators of bone growth, and might also be helpful anabolic agents for counteracting the negative effects of GCs. Therefore, we studied the interaction of GCs in combination with a single dose of either PTH or T(4) on GC-induced growth retardation. Dexamethasone (Dex) treatment of mice for four weeks induced a significant growth inhibition of body length and weight and weights of several organs. PTH or T(4) alone did not affect the normal growth pattern. However, T(4) could partially restore the Dex-induced growth inhibition, whereas PTH could not. Although PTH did not affect total body growth, it did affect the height of the proliferative zone, which could be counteracted by Dex. This contrasts with T(4) treatment alone or in combination with Dex, which both resulted in a disturbed morphology of the growth plate. IGF-I mRNA, one of the mediators of longitudinal bone growth, was present in proliferative and hypertrophic chondrocytes. However, its expression was not affected by any of the treatments. In conclusion, T(4) but not PTH can partially counteract the effects of Dex on general body growth, with possible implications for future treatments of GC-induced growth retardation. Additionally, both T(4) and PTH, alone or in combination with Dex, have differential effects on the morphology of the growth plate.

Dexamethasone differentially inhibits thyroxine- or growth hormone-induced body and organ growth of Snell dwarf mice.

Supraphysiological doses of glucocorticoids cause growth retardation in both animals and humans. Many studies have addressed the interaction of glucocorticoids with the GH/IGF system, but little is known about the effect of glucocorticoids on T(4)-stimulated growth. The Snell dwarf mouse is deficient in GH, thyroid-stimulating hormone, and prolactin and therefore allows the study of the effect of glucocorticoids on the growth induced by GH and T(4) without their mutual interaction. Four weeks of treatment with T(4) (1 micro g/d) or human GH (50 mU/d) equally increased nose-tail length (3.1 +/- 0.1 cm and 3.0 +/- 0.2 cm, respectively). Dexamethasone (DXM) had much less impact on T(4)-stimulated growth than on GH-induced growth (T(4) + DXM: 2.4 +/- 0.1 cm vs. GH+ DXM: 1.4 +/- 0.1 cm). Similar data were obtained for body weight gain. T4 and GH had a different effect on the weight of various organs: GH caused a higher increase in liver and lumbar vertebrae weight, and T(4) was a better stimulator for kidney (P < 0.05), thymus, and spleen growth. Remarkably, T(4)-stimulated growth of the organs was less affected by DXM than GH-induced organ growth. GH even potentiated the growth inhibition by DXM in the thymus and tibia. In conclusion, T(4)-stimulated growth in Snell dwarf mice is less affected by DXM than growth stimulated by GH