Environmental Estrogens Stimulate Gene Transcription in the Prolactin Promoter

Winnifred Monica Bryant,Sarah Korb,Fong Lee,Anthonia Arikawe

doi:10.5539/ijb.v2n1p35

Abstract

The ability of environmental estrogens to regulate gene transcription on model and physiologically complex promoter was examined in GH3 cells, a pituitary cell line. In transient transfection studies, the pGL3 model promoter and the physiologically complex prolactin promoter were both responsive to the xenoestrogen bisphenol A and the phytoestrogen daidzein in a dose related manner. These transcriptional responses were mediated by estrogen receptors, as responses were ameliorated in the presence of ICI 180, 782, a pure antiestrogen. Cotransfection of Pit-1 significantly enhanced the transcriptional response of the prolactin promoter to stimulation by environmental estrogens. The nature and magnitude of transcriptional responses to estradiol sensitive genes following challenge by environmental estrogens is likely dependent on regulatory elements found in the promoter and their ability to recruit transcription factors.

Highlights

The steroid hormone 17 -estradiol (E2) is the primary estrogen generated in the ovaries (Gruber et al, 2002) and regulates gene expression in a number of target tissues
As cells were treated with increasing concentrations of BPA (10-15M-10-6M), promoter activity was observed to increase in a dose related fashion, though response to highest dose of BPA was not significantly different that of E2 alone (3.23 fold increase in activity as compared to vehicle treated control)
Daidzein was more effective at stimulating promoter activity than BPA (4.6 fold at maximum dose as compared to control) and stimulated a slightly more robust response increase in pGL3 activity than E2

Summary

Introduction

The steroid hormone 17 -estradiol (E2) is the primary estrogen generated in the ovaries (Gruber et al, 2002) and regulates gene expression in a number of target tissues. This gives way to physiological effects which include cell differentiation, cell proliferation, and protection from pathological insult (Gruber et al, 2002, Heldring et al, 2007). The most significant reproductive neuroendocrine event mediated by E2 is the initiation of the luteinizing hormone (LH) surge in mammals during the estrous or menstrual cycle. ERǂҏ and ERǂ can be detected but ER.ҏ is the predominantly expressed in lactotrophs and gonadotrophs (Gonzalez et al, 2008)

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