In vitro responses to 17β-estradiol throughout pubertal maturation in female human bone cells

To test the hypothesis that bone sensitivity to estrogens differ with the pubertal status, we cultured human osteoblasts (hOBs) from 14 girls (3-18 years) and examined the effects of repeated weekly doses of 17 beta-estradiol (E-2, 10 pM-10 nM) on estradiol receptor (ER) and progesterone receptor (PR) expression, type I procollagen (PICP) and osteocalcin (BGP; bone Gla protein) production, and alkaline phosphatase (ALP) activity. The bone samples were divided into two equal groups according to the pubertal status and plasma E-2 level of the donor. The two groups were significantly different for age (9 +/- 1 and 15 +/- 1 years), pubertal status (Tanner stages I-III and IV-V), and plasma E-2 concentrations (17 +/- 3 and 49 +/- 4 pg/ml), ER and PR were expressed and not influenced by the sexual maturation in untreated cells. E-2 increased ER in the two groups with nanomolar doses. Picomolar doses did not significantly increase ER expression but led to significant differences in the percentage of cells expressing ER in premenarchial (33%) and postmenarchial (7%) hOB cultures. In the two groups, E-2 had no clear effect on PR expression, ALP activity, nor BGP production. But repeated weekly doses of E-2 significantly influenced PICP production at picomolar doses. This effect depended upon the sexual maturation of the donor. E-2 decreased PICP in premenarchial cultures and increased PICP in postmenarchial cultures. Thus, E-2 modulates in vitro human bone cell metabolism and probably their phenotype and has different effects, depending on the pubertal status of the donor. Unlike what could have been expected, prepubertal and early pubertal hOBs appear to be specifically sensitive to picomolar doses of E-2, suggesting that this hormone is a crucial regulator of bone metabolism even before puberty.