Endocrine Abstracts

Vitamin D receptors are widely expressed in the skeletal system, and vitamin D and its metabolites and analogs, exert a variety of biological activities such as regulation of cellular proliferation and differentiation, cell calcium transients and energy metabolism in vitro. The latter is exerted through the control of the brain type isozyme of creatine kinase specific activity (CK), which serves to provide a readily available reservoir for ATP generation under increased workload. We have previously reported that pretreatment with the less-calcemic analog of vitamin D JKF 1624F₂-2 (JKF) upregulated the responsiveness to estrogenic compounds via modulation of the expression of mRNA for ERs. In the present study we analyzed the mutual modulation of the vitamin D system and estrogens in human cultured female bone cells (hObs). We compared the effects of the different hormones on the expression of mRNA for both ERα and ERβ and 1α 25 vitamin D hydroxylase in hObs. In pre-menopausal hObs all hormones tested increased 1α 25 vitamin D hydroxylase mRNA expression whereas in post-menopausal hObs biochainin A had no effect and genistein is decreasing this mRNA expression. All these compounds increased the expression of mRNA for ERα in pre-menopausal hObs whereas in post-menopausal hObs biochainin A had no effect and estradiol and raloxifene decreased this mRNA expression. ERβ in both hObs was increased only by carboxy-biochainin A and raloxifene and all other hormones decreased ERβ. In conclusion vitamin D analogs and estrogens modulate each other’s activity in hObs. The different hormones modulate the response to estradiol by direct modulation of ERs mRNA expression and by indirect modulation via increasing vitamin D in bone cells leading to modulation of responsiveness by this system as well. Whether or not this property can be utilized to achieve better bone protection remains subject to further studies.