Ovariectomized (OVX) rats are commonly used for the investigation of estrogenic compounds in vivo. We previously showed that estrogen treated OVX animals apparently respond differently to Genistein (GEN) treatment than hormonally intact animals. An observation, that indicated that progestins might interfere in the estradiol (E2)GEN interaction.
As the molecular effects of GEN seem to be modified by progesterone (P4), its role should be determined in presence and absence of E2. Therefore, we performed an animal experiment with adult Wistar rats which were either OVX or sham operated. These animals were s.c. treated with E2 (1 μg/kg BW and d), P4 (40 mg/kg BW and d) or GEN (10 mg/kg BW and d) either as single compounds or as their respective mixtures. As readout, we assessed the mRNA and protein expression pattern of the progesterone receptor (PGR) as well as of both estrogen receptor subtypes.
Performing immunohistochemical staining of OVX rat uterus cross-sections, we generally found higher PGR protein expression levels in the luminal epithelium compared to the stroma. Following E2 treatment, the PGR expression level was increased in both luminal epithelium and stroma respectively. The comparison of the two uterine tissue compartments showed, that the expression increases predominantly in the stroma (twofold increase). In contrast to the other combinatorial treatments involving E2 (E2P4 and E2P4GEN), the E2-free combination of P4GEN showed no effect on overall PGR expression, although there might be a shift from epithelial to the stromal expression.
In conclusion, our results indicate that E2 triggered estrogenic responses on PGR expression are detectable throughout all uterine tissue compartments. With regard to the fact that they are more pronounced in the stroma, compared to the luminal epithelium, the importance of the stroma as a hormone response regulating tissue is accentuated.
30 Apr - 04 May 2011
European Society of Endocrinology