Catch-up growth after hypothyroidism is caused by delayed growth plate senescence

Rose Marino, Anita Hegde, Kevin M. Barnes, Lenneke Schrier, Joyce A. Emons, Ola Nilsson, Jeffrey Baron

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1820-1828
Number of pages9
JournalEndocrinology
Volume149
Issue number4
DOIs
StatePublished - Apr 1 2008

ASJC Scopus subject areas

  • Endocrinology

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    Marino, R., Hegde, A., Barnes, K. M., Schrier, L., Emons, J. A., Nilsson, O., & Baron, J. (2008). Catch-up growth after hypothyroidism is caused by delayed growth plate senescence. Endocrinology, 149(4), 1820-1828. https://doi.org/10.1210/en.2007-0993