EVIDENCE FOR ESTROGENIC REGULATION OF HEAT-SHOCK PROTEIN EXPRESSION IN HUMAN ENDOMETRIUM AND STEROID-RESPONSIVE CELL-LINES

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 oner the whole menstrual c ycle and in short-term cultures of steroid-responsive (T47-D) and unre sponsive (HRT-18) cell lines exposed to oestradiol and progesterone ov er a 24-h incubation period. In endometrium, oestrogen and progesteron e receptors followed the expected patterns of expression at the protei n level during the menstrual cycle and also showed a positive correlat ion of expression with each other throughout (r=0.514), Of the HSPs on ly HSP 90 alpha expression correlated positively with oestrogen recept or (r=0.687), while HSP 70a expression, which peaked in the late secre tory stage, displayed a significantly inverse correlation with HSP 90 beta expression (r=-0.526). All p values < 0.05. In T47-D cell culture s, oestrogen receptor expression was stimulated transiently by oestrad iol (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 w ere stimulated by oestradiol, Progesterone generally depressed HSP 90 alpha expression and simultaneous addition of both oestradiol and prog esterone to the culture medium was antagonistic to HSP 90 alpha expres sion. No clear effect of agonist addition on HSP mRNA expression was a pparent in the HRT-18 cultures. A possible mechanism for observed oest rogenic effects on HSP expression is put forward.