Evidence for oestrogenic regulation of heat shock protein expression in human endometrium and steroid-responsive cell lines

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Gene amplification with target-specific primers (reverse-transcription polymerase chain reaction (RT-PCR)) was used to monitor the relative expression of oestrogen and progesterone receptor mRNAs alongside the mRNAs for heat shock proteins HSP 90 alpha, HSP 90 beta and HSP 70a in normal samples of human endometrial tissue over the whole menstrual cycle and in short-term cultures of steroid-responsive (T47-D) and unresponsive (HRT-18) cell lines exposed to oestradiol and progesterone over a 24-h incubation period. In endometrium, oestrogen and progesterone receptors followed the expected patterns of expression at the protein level during the menstrual cycle and also showed a positive correlation of expression with each other throughout (r = 0.514). Of the HSPs only HSP 90 alpha expression correlated positively with oestrogen receptor (r = 0.687), while HSP 70a expression, which peaked in the late secretory stage, displayed a significantly inverse correlation with HSP 90 beta expression (r = -0.526). All p values < 0.05. In T47-D cell cultures, oestrogen receptor expression was stimulated transiently by oestradiol (10(-7) mol/l) and more persistently by progesterone (10(-7) mol/l). Progesterone receptor expression was depressed by progesterone and weakly stimulated by oestradiol. HSP 70a and HSP 90 alpha expression were stimulated by oestradiol. Progesterone generally depressed HSP 90 alpha expression and simultaneous addition of both oestradiol and progesterone to the culture medium was antagonistic to HSP 90 alpha expression. No clear effect of agonist addition on HSP mRNA expression was apparent in the HRT-18 cultures. A possible mechanism for observed oestrogenic effects on HSP expression is put forward.