- The steroid hormone estrogen plays a crucial role in regulating certain mammalian tissues, especially female reproductive systems. Estrogen effects physiological changes in the cell by altering transcription activity for certain target genes, as a consequence of interactions between estradiol-17β (E2) and its nuclear receptor (nER). This mechanism of cellular control is referred to as classical genomic regulation. Changes take hours to manifest, since they depend on gradual changes in protein populations. However, rapid cellular changes – such as activation of MAPK pathways – have been observed within seconds of E2 exposure in vivo. These changes cannot be explained by classical mechanisms of genomic regulation, and thus are defined as nongenomic regulation. Such regulation is understood to be mediated by specific receptors localized to the plasma membrane (PM).
In studies conducted in vitro and in vivo, in murine models, the specific PM-localized E2 receptor (mER) responsible for mediating nongenomic regulation has been shown to be a specially translocated subpopulation of nER. However, these findings have yet to be corroborated in vivo in animals larger than mice. The specific purpose of the present study was to ascertain whether a correlation could established between levels of nER expression in the nucleus and expression of mER in the PM in cells of the ovine endometrium, comparing groups of ewes treated with either E2 or progesterone (P4). The hypothesis was that significant increases in levels of nER of E2 treated ewes would be reflected by significant increases in mER, as compared to P4 treated ewes.
Ovariectomized ewes were treated with E2 and progesterone (P4) to condition the endometrium, a rich source of endogenous nER. The ewes were then divided into two treatment groups. Group 1 received additional E2 injections, known to elevate cellular nER levels, while group 2 received additional P4 injections, known to suppress nER levels. Results demonstrated significant increases in nER correlated with significant increases in mER in E2 treated ewes, as compared to P4 treated ewes, which supports the study’s hypothesis. These findings set the stage for further investigations into explicitly characterizing the nature of the mER in an ovine model, as well as continued exploration of nongenomic regulatory responses.