Multicentric Graduate Studies Program in Physiological Sciences, Brazilian Physiological Society/Univ. Estadual Paulista, SP, Brazil.
Bone. 2012 Apr;50(4):893-900. doi: 10.1016/j.bone.2011.12.009. Epub 2011 Dec 24.
This study investigated the role of neonatal sex steroids in rats on sexual dimorphism in bone, as well as on leptin and corticosterone concentrations throughout the lifespan. Castration of males and androgenization of females were used as models to investigate the role of sex steroids shortly after birth. Newborn Wistar rats were divided into four groups, two male groups and two female groups. Male pups were cryoanesthetized and submitted to castration or sham-operation procedures within 24 h after birth. Female pups received a subcutaneous dose of testosterone propionate (100 μg) or vehicle. Rats were euthanized at 20, 40, or 120 postnatal days. Body weight was also measured at 20, 40, and 120 days of age, and blood samples and femurs were collected. The length and thickness of the femurs were measured and the areal bone mineral density (areal BMD) was determined by dual-energy X-ray absorptiometry (DEXA). Biomechanical three-point bending testing was used to evaluate bone breaking strength, energy to fracture, and extrinsic stiffness. Blood samples were submitted to a biochemical assay to estimate calcium, phosphorus, alkaline phosphatase, leptin, and corticosterone levels. Weight gain, areal BMD and bone biomechanical properties increased rapidly with respect to age in all groups. In control animals, skeletal sexual dimorphism, leptin concentration, and dimorphic corticosterone concentration patterns were evident after puberty. However, androgen treatment induced changes in growth, areal BMD, and bone mass properties in neonatal animals. In addition, neonatally-castrated males had bone development and mechanical properties similar to those of control females. These results suggest that the exposure to neonatal androgens may represent at least one covariate that mediates dimorphic variation in leptin and corticosterone secretions. The study indicates that manipulation of the androgen environment during the critical period of sexual differentiation of the brain causes long-lasting changes in bone development, as well as serum leptin and corticosterone concentrations. In addition, this study provides useful models for the investigation of bone disorders induced by hypothalamic hypogonadism.
本研究探讨了新生大鼠性激素在骨骼性别二态性以及整个生命周期中瘦素和皮质酮浓度中的作用。通过对雄性大鼠进行去势和雌性大鼠进行雄激素化处理，作为出生后短期研究性激素作用的模型。新生 Wistar 大鼠分为两组雄性组和两组雌性组。雄性幼鼠在出生后 24 小时内冷冻麻醉并进行去势或假手术处理。雌性幼鼠接受丙酸睾酮（100μg）或载体的皮下注射。大鼠在 20、40 或 120 日龄时安乐死。体重也在 20、40 和 120 日龄时测量，并采集血液样本和股骨。测量股骨的长度和厚度，并通过双能 X 射线吸收法（DEXA）确定骨面积密度（骨面积 BMD）。使用生物力学三点弯曲试验评估骨断裂强度、断裂能量和外骨骼刚度。采集血液样本进行生化分析，以估计钙、磷、碱性磷酸酶、瘦素和皮质酮水平。在所有组中，体重增加、骨面积 BMD 和骨生物力学特性均随年龄迅速增加。在对照动物中，青春期后骨骼性别二态性、瘦素浓度和二态性皮质酮浓度模式明显。然而，雄激素处理会改变新生动物的生长、骨面积 BMD 和骨量特性。此外，新生去势雄性大鼠的骨发育和机械特性与对照雌性大鼠相似。这些结果表明，暴露于新生雄激素至少可以代表介导瘦素和皮质酮分泌性别二态性的一个协变量。该研究表明，在大脑性分化的关键时期改变雄激素环境会导致骨发育以及血清瘦素和皮质酮浓度的持久变化。此外，该研究为研究下丘脑性性腺功能减退症引起的骨疾病提供了有用的模型。
