Affected skeletal growth but normal bone mineralization in rat offspring after prenatal dexamethasone exposure D Swolin-Eide 1,2 , J Dahlgren 2,3 , C Nilsson 3 , K Albertsson Wikland 2 , A Holmäng 3 and C Ohlsson 1 1 Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden 2 Pediatric Growth Research Center, Institute for the Health of Women and Children, Sahlgrenska University Hospital, S-416 85 Göteborg, Sweden 3 Wallenberg Laboratory, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden (Requests for offprints should be addressed to D Swolin-Eide, Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Gröna stråket 8, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden; Email: diana.swolin@medic.gu.se) Abstract Events occurring early in life or prenatally are able to play important roles in the pathogenesis of diseases in adult life. Different sorts of stress or hormonal influences, during particular periods of pregnancy, may result in persisting or transient changes in physiology. Glucocorticoids are used for the treatment of a variety of diseases, to promote organ maturation and to prevent preterm delivery. Glucocorti- coids are also known to affect skeletal growth and adult bone metabolism. The aim of the present study was to investigate whether exposure to dexamethasone (Dex) during fetal life has any effect on skeletal growth and/or bone mineral density in adult rat offspring. Pregnant rats were given injections of either Dex (100μg/kg) or vehicle on days 9, 11 and 13 of gestation. Dex-exposed male but not female rat offspring showed transient increases in crown–rump length and tibia and femur lengths at 3–6 weeks of age. In contrast, the cortical bone dimensions were altered in 12-week-old female but not male Dex-exposed offspring. The areal bone mineral densities of the long bones and the spine, as determined by dual X-ray absorptiometry, and trabecular as well as cortical volumetric bone mineral density, as measured using peripheral quantitative computerized tomography, were unchanged in both male and female Dex-exposed offspring. In conclusion, prenatal Dex exposure affects skeletal growth in a gender-specific manner, while the minerali- zation of bones is unaffected in both male and female offspring. Journal of Endocrinology (2002) 174, 411–418 Introduction It has been shown that events occurring early in life or prenatally are able to play important roles in the patho- genesis of adult disease in both humans and animals (Barker et al. 1993, Benediktsson et al. 1993). The process whereby a stimulus or insult at a sensitive or critical period of development has long-term effects is termed ‘program- ming’ (Lucas 1991). Dexamethasone (Dex) is a potent synthetic glucocorticoid lacking mineralocorticoid activity, and it passes through the placenta without being inacti- vated by the enzyme 11-hydroxysteroid dehydrogenase. Exposure to Dex late in pregnancy has been claimed to result in a reduced birth weight, and in hyperinsulinaemia and hypertension in adulthood (Benediktsson et al. 1993, NIH 1995). A recent clinical study suggests that low birth weight is associated with lower adult bone and muscle mass which indicate that the risk of osteoporosis in later life might be programmed by genetic or environmental influences during gestation (Gale et al. 2001). Further- more, a low birth weight and leanness at birth have been shown to be associated with insulin resistance in children and adolescents (Ornoy & Altshuler 1976, Hofman et al. 1997, Robinson et al. 2000). A recent study has shown that prenatal exposure to Dex leads to increased fat depots in the adult rat. One of the possible mechanisms involved is programming of the fetal hypothalamo–pituitary–adrenal (HPA) axis (Matthews 2000). The HPA axis, which is central to the integration of the individual’s endocrine and behavioural response to stress, appears to be highly sensi- tive to an excess of glucocorticoids during development (Clark 1998). Glucocorticoids are widely used to treat inflammatory diseases, asthma, and as immunosuppressives. High endo- genous levels of cortisol are seen during infections and stressful events. Furthermore, 10% of pregnant women in North America and Europe are treated with synthetic glucocorticoids between weeks 24 and 34 of gestation to promote fetal lung maturation in fetuses at risk of being delivered prematurely (Matthews 2000). Long-term 411 Journal of Endocrinology (2002) 174, 411–418 0022–0795/02/0174–411  2002 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology.org