A mathematical approach for the transactivation of hERalpha.
Several reports over the last few years have documented the dose-response curve for steroid hormone induction of gene transcription as a modulated property of a given receptor-agonist complex that varies with the changing concentration of a variety of factors including: homologous receptor, co-activators, co-repressors and selected co-factors. In each report, the dose-response curves are sigmoidal and show an excellent fit with the curve generated by Michaelis-Menten kinetics. In addition, even the overall function of human oestrogen receptors (hERs) can show a similar graph for the determination of sex versus oestrogen compounds in reptiles. Thus, the kinetic properties of the simple bimolecular reaction of A+B-->C appear, surprisingly, to be sufficient to describe the dose-response curve of the multi-step process of steroid-regulated gene induction that involves several molecules. Any advance in explaining why the dose-response curve for steroid-regulated gene expression is sigmoidal would assist in understanding what parameters are key factors of the dose-response curve and can benefit in the design of new oestrogenic substances. We have constructed and analysed a multi-step model of hER-induced gene transcription that explains the multiple forms of a simple dose-response curve in an in vitro transcription system.
Castano
Enrique
E
Unidad de Bioquímica y Biología Molecular de Plantas, Centro de Investigación Científica de Yucatán, Calle 43, No. 130, Colonia Chuburná de Hidalgo CP 97200 Mérida, Yucatán, Mexico. enriquec@cicy.mx
Flores-Saaib
Ruben D
RD
D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008433:Mathematics; D008957:Models, Genetic; D015233:Models, Statistical; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D047628:Estrogen Receptor alpha; D011994:Recombinant Proteins