Catch-Up Growth after Hypothyroidism Is Caused by Delayed Growth Plate Senescence
- 3 January 2008
- journal article
- other
- Published by The Endocrine Society in Endocrinology
- Vol. 149 (4), 1820-1828
- https://doi.org/10.1210/en.2007-0993
Abstract
Catch-up growth is defined as a linear growth rate greater than expected for age after a period of growth inhibition. We hypothesized that catch-up growth occurs because growth-inhibiting conditions conserve the limited proliferative capacity of growth plate chondrocytes, thus slowing the normal process of growth plate senescence. When the growth-inhibiting condition resolves, the growth plates are less senescent and therefore grow more rapidly than normal for age. To test this hypothesis, we administered propylthiouracil to newborn rats for 8 wk to induce hypothyroidism and then stopped the propylthiouracil to allow catch-up growth. In untreated controls, the growth plates underwent progressive, senescent changes in multiple functional and structural characteristics. We also identified genes that showed large changes in mRNA expression in growth plate and used these changes as molecular markers of senescence. In treated animals, after stopping propylthiouracil, these functional, structural, and molecular senescent changes were delayed, compared with controls. This delayed senescence included a delayed decline in longitudinal growth rate, resulting in catch-up growth. The findings demonstrate that growth inhibition due to hypothyroidism slows the developmental program of growth plate senescence, including the normal decline in the rate of longitudinal bone growth, thus accounting for catch-up growth.Keywords
This publication has 29 references indexed in Scilit:
- Cellular Senescence in Cancer and AgingCell, 2007
- Fundamental limits on longitudinal bone growth: growth plate senescence and epiphyseal fusionTrends in Endocrinology & Metabolism, 2004
- Estrogen supplementation modulates effects of the endocrine disrupting pollutant PCB126 in rat bone and uterus: Diverging effects in ovariectomized and intact animalsToxicology, 2004
- Osteoclast differentiation and characteristic trabecular bone formation during growth plate destruction in osteoprotegerin-deficient mice.Journal of Electron Microscopy, 2003
- Wnt5aandWnt5bexhibit distinct activities in coordinating chondrocyte proliferation and differentiationDevelopment, 2003
- The Role of the Resting Zone in Growth Plate ChondrogenesisEndocrinology, 2002
- Catch-Up Growth Is Associated with Delayed Senescence of the Growth Plate in RabbitsPediatric Research, 2001
- Association of Chondroadherin with Collagen Type IIOnline Journal of Public Health Informatics, 2001
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutationsNature Genetics, 2000