Figure 1.

Schematic representation of the interplay between nutritional status and endocrine regulators of growth: growth hormone (GH) resistance induced by prolonged fasting impairs GH direct and insulin-like growth factor I (IGF-I) mediated action on chondrocytes. The increased secretion of fibroblast growth factor 21 (FGF21) by liver and adipose tissue in malnutrition contributes to GH resistance by reducing hepatic GH receptors expression and disrupting GH action in the growth plate. Insulin promotes growth by acting both directly on chondrocytes and indirectly, stimulating IGF-I production. Leptin, produced by adipose tissue, stimulates growth hormone-releasing hormone (GHRH) secretion by the hypothalamus and exerts a direct peripheral growth-promoting effect in the growth plate by stimulating chondrocyte proliferation and differentiation. Hypothalamic melanocortin 3 receptor (MC3R) integrates signals of metabolic status that affect body growth and sexual maturation. Micronutrients such as zinc, copper, calcium, vitamin D and macronutrients such as aminoacids, in particular leucine, exert a direct effect on the epiphyseal growth plate by influencing chondrocyte differentiation and proliferation.