Hypothalamic Suppression during Adolescence Varies by Bone Envelope

Abstract

Purpose The purposes of this study were to suppress estradiol levels in adolescent (postpubertal rats) using gonadotropin-releasing hormone antagonist (GnRH-a) injections and to determine the changes in bone structure and mechanical strength. Methods In an Institutional Animal Care and Use Committee–approved study, female rats at 23 d of age were assigned to a baseline group (BL65; n = 10) sacrificed on day 65, a control group (Control; 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-d period from 65 to 90 d of age (2.5 mg·kg−1 per dose). Results Body weights were similar on day 65; however, the AMEN group was significantly heavier than the Control group (17%, P = 0.001) on day 90. In the AMEN rats relative to the Control group, plasma estradiol levels were reduced by 36% (P = 0.0001) and plasma insulin-like growth factor 1 levels were 24% higher (P = 0.003). In the femur, there was no change in periosteal bone apposition or total cross-sectional area. The marrow area increased by 13.7% (P = 0.05) resulting in a 7.8% decrease in relative cortical area (P = 0.012), and endocortical bone formation rate increased by 39.4% (P = 0.04). Trabecular volume and number decreased by 51.5% (P = 0.0003) and 49.5% (P = 0.0003), respectively. The absolute peak moments of the tibiae and femurs were unchanged in the AMEN group relative to the Control group, but these were reduced by 8.8% (P = 0.03) and 7.5% (P = 0.09), respectively, when normalized by body weight. Conclusions Suppression of estradiol by 25 d of GnRH-a administration to 65-d-old (postpubertal) 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 because of increases in body weight or in insulin-like growth factor 1 concentrations.

Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

“…Lower uterine weights are indicative of suppressed estrogen release from the ovaries. Although estrogen levels were not measured in the current study, previous data corroborates suppressed serum estradiol levels using the GnRH-a injection protocol in pre-pubescent female rats ( Yingling & Khaneja, 2006 ; Yingling et al, 2007 ; Yingling & Taylor, 2008 ; Saine et al, 2011 ). In addition, serum CTX levels were significantly increased by 59% in the GnRH-a group an indicator of increased bone resorption also associated with suppressed estrogen secretion.…”

Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats

“…An increase in marrow area can offer increased torsion strength and flexibility if cortical thickness and bone diameter are maintained, since bending strength of bone is exponentially related to its diameter [79]. However, in the mature HRLF rats, the cortical thinning was due to a lack of a compensatory increase in the periosteal perimeter as the endosteal perimeter increased.…”