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Glucocorticoids, thyroid hormone and growth hormone interactions: implications for the growth plate
T Siebler1, H Robson, S M Shalet
1University Children's Hospital, University of Leipzig, Germany.
Insights
Childhood linear growth relies on the growth plate, with growth hormone (GH) and insulin-like growth factor (IGF)-I playing key roles. Recent research highlights local IGF-I actions and direct hormone regulation within the growth plate.
Area of Science:
- Pediatric endocrinology
- Skeletal biology
- Growth regulation
Background:
- Linear growth in children is crucial for development.
- Endochondral ossification in the growth plate drives longitudinal bone growth.
- Growth hormone (GH) and insulin-like growth factor (IGF)-I are primary regulators, with glucocorticoids (GC) and thyroid hormone (T3) also contributing.
Purpose of the Study:
- To investigate the roles of GH, IGF-I, GC, and T3 in regulating linear growth.
- To clarify the mechanisms of hormone action within the epiphyseal growth plate.
- To evaluate the somatomedin hypothesis versus local autocrine/paracrine pathways.
Main Methods:
- Analysis of hormone imbalances during childhood growth.
- Studies utilizing genetically modified mouse models.
- Examination of IGF-I and its receptor expression in the growth plate.
Main Results:
- Evidence supports a significant autocrine/paracrine pathway for GH and IGF-I in growth.
- Direct effects of GC and T3 on endochondral ossification are confirmed.
- The growth plate acts as a central hub for converging hormonal signals controlling linear growth.
Conclusions:
- Local IGF-I action is a critical determinant of endochondral ossification.
- GH, GC, and T3 directly influence IGF-I and its receptor expression in the growth plate.
- The epiphyseal growth plate integrates multiple hormonal inputs to control childhood linear growth.
Abstract:
Linear growth occurs during childhood and results from endochondral ossification in the growth plate. Prepubertal growth is primarily regulated by growth hormone (GH) and insulin-like growth factor (IGF)-I, with important contributions from glucocorticoids (GC) and thyroid hormone (T(3)). The somatomedin hypothesis proposed that GH stimulates hepatic IGF-I production, which then regulates growth via IGF-I receptor expressing chondrocytes in an endocrine fashion. Recent studies indicate that locally acting IGF-I is a key determinant of endochondral ossification and that GH, GC and T(3) regulate expression of IGF-I and its receptor in the growth plate directly. Analysis of hormone imbalance during childhood and studies of genetically modified mice provide support for an important GH and IGF-I autocrine/paracrine pathway and for direct effects of GC and T(3) during endochondral ossification. Thus, the epiphyseal growth plate is a key site for convergent hormone action that mediates the control of linear growth.