The Influence of Thyroid Hormone on Growth Hormone Secretion and Action

Abstract

Thyroid hormone (TH) is required for normal growth hormone (GH) synthesis and secretion. Both thyroid hormone deficiency (hypothyroidism) and thyroid hormone excess (hyperthyroidism) are associated with alterations in bone development and linear growth in children. This review summarizes the current understanding of the mechanisms mediating the interaction between thyroid hormone and growth hormone, at the level of secretion and action, as well as the clinical implications. In rodent models, thyroid hormone deprivation results in reduced growth hormone mRNA levels in the pituitary, as well as reduced growth hormone-releasing hormone and growth hormone secretion. Thyroid hormone is important for a normal response to agents that stimulate GH secretion, including thyrotropin-releasing hormone and growth hormone-releasing hormone, and stimulation from exercise, starvation, and critical illness. In the few clinical studies available, prompt normalization of thyroid status generally prevents long-term impact on bone development and linear growth, but a prolonged period of time without treatment has been associated with irreversible alterations. Resistance to thyroid hormone (RTH) is a clinical syndrome classically linked to mutations in the thyroid hormone receptor β gene, TRβ. Families have recently been identified with mutations in the thyroid hormone receptor α gene, TRα. Abnormalities of growth and development are seen in both forms of RTH but are more pronounced in individuals with mutation in the TRα gene, in which growth deficits and bony deformities are key clinical features. These clinical syndromes, as well as the study of mouse models with these mutations, have resulted in the identification of key actions of thyroid hormone on bone and linear growth and have expanded our understanding of the interaction of thyroid hormone with the secretion and action of growth hormone and IGF-I.