Hypothalamic Suppression during Adolescence Varies By Bone Envelope


Saine, M.E.; Barbe, M.F.; Agah, M.R.; Yingling, V.R.


The purpose of this study was to suppress estradiol levels in adolescent (post pubertal rats) using gonadotropin releasing hormone antagonist (GnRH-a) injections and determine the changes in bone structure and mechanical strength. In an IACUC approved study, female rats at 23 days of age were assigned to a baseline group (BL65) (n=10) sacrificed on day 65, a control group (C) (n=15) sacrificed on day 90, or an experimental group (AMEN) (n=9) sacrificed on day 90 that received daily injections of GnRH-a for a 25 day period from 65 to 90 days of age (2.5 mg/kg/dose). Body weights were similar on day 65 however, the AMEN group was significantly heavier than C (17%, p=.001) on day 90. In the AMEN rats relative to C, plasma estradiol levels were reduced by 36% (p=.0001), and plasma IGF-1 levels were 24 % higher (p=.003). In the femur, there was no change in periosteal bone apposition or total cross-sectional area. The marrow area increased by 13.7% (p=.05) resulting in a 7.8% decrease in relative cortical area (p=.012), and endocortical bone formation rate increased by 39.4% (p=.04). trabecular volume and number decreased by 51.5% (p=.0003) and 49.5% (p=.0003), respectively. The absolute peak moment of the tibiae and femurs were unchanged in the AMEN group relative to C, but were reduced by 8.8% (p=.03) and 7.5% (p=.09) respectively when normalized by body weight. Suppression of estradiol by 25 days of GnRH antagonist administration to 65-day old (post pubertal) rats, reduced trabecular volume and number by about 50%, increased endocortical bone turnover, and reduced relative cortical thickness without changing tibial and femoral total area. These changes in bone structure were associated with no change in absolute mechanical strength possibly due to increases in body weight or in IGF-1 concentrations.

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