Objective and hypotheses: The purpose was to get the basic data of optimum serum concentration of oestrogen in pubertal growth spurt, minimising the decrease of bone mineral density or acceleration of epiphyseal closure of long bones.
Method: i). Fifteen female S.D. rats (4-week aged) were ovariectomised to inhibit their endogenous oestrogen effect and randomly divided into three groups. After 1 week, the group 1 were injected subcutaneously with sesame oil, as a control, group 2 were with 100 μg/kg/week of oestradiol depo as a high-dose, and group 3 were with 200 μg/kg/week of it as a super-high-dose for 10 weeks on their posterior neck area. ii) Their crown-lump length, body weight, and bone mineral density of spine and long bones were checked weekly from 1 week before through 10 weeks after injections. iii) Serum levels of GH and oestradiol were checked with ELISA before and after injections. iv) After 10 weeks of injections, they were euthanized, pituitary glands were dissected and their pituitary Gh1 mRNA levels were checked with quantitative RT-PCR. v) Their proximal tibia were dissected and stained with hematoxylin-eosin. vi) The thicknesses of epiphyseal plate including proliferative and hypertrophic zone of the proximal tibias were measured in 20 evenly divided sites with microscope. vii) Statistical analyses were done among the 3 groups before and after injections using ANOVA with multiple comparisons for auxological data, and Kruskall Wallis test for serum levels of GH, oestradiol, and pituitary Gh1 mRNA levels with SPSS ver.13.0.
Results: i) There were no significant differences in body lengths among 3 groups. ii) The body weights were decreased, and the bone mineral densities were increased in group 3 but there were no significant differences. iii) Serum GH levels and pituitary Gh1 expressions were significantly increased in group 3. iv) There was no significant difference in the thickness of total epiphyseal plate, proliferative zone, but that of hypertrophic zone of the epiphyses was significantly increased in group 3.
Conclusion: i) GH secretion and Gh1 gene expression were increased after super-high dose oestrogen treatment. ii) There were tendencies that body weight is negative and bone mineral density is positive relation with oestrogen dosage, but with no significant differences. iii) The thickness of hypertrophic zone in epiphyseal plate was relatively increased after super-high-dose oestrogen treatment, maybe because of increased transdifferentiation of osteoblast to osteocyte. iv) The effects of oestrogen on epiphyseal plate in rodents may be different with human.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology