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

Abstract

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.

Hormone replacement therapy increases levels of antibodies against heat shock protein 65 and certain species of oxidized low density lipoprotein

“…We found a significant increase in antibody response against Hsp 65 although the mechanism involved remains unclear. Nevertheless, this result agrees with a recent report demonstrating that estrogen was able to regulate the expression of Hsp (both the 90 and 70 subclasses) in human endometrium and several human cell lines (9). How antibodies against Hsp or cross-reactive antibodies against Hsp could influence the genesis and progression of CAD requires further investigation.…”

Estrogen and Androgen Protection of Human Neurons against Intracellular Amyloid 1-42 Toxicity through Heat Shock Protein 70

“…Several studies have found increased expression of Hsp70 in various hormone-treated cell types (Tang et al, 1995;Jones et al, 2000;Lu et al, 2002;Gehring, 2004). The fact that Hsp70 can completely prevent iA␤ 1-42 -mediated toxicity indicates only that Hsp70 is sufficient for neuroprotection against iA␤ 1-42 toxicity but does not rule out the possibility that other effects of the steroid hormones on neurons could also be neuroprotective.…”

Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.

“…The ability of estrogen to alter levels of the uterine hsp90 isoforms hsp90α and hsp90β has been demonstrated previously (Shyamala et al 1989). Estrogen also regulates mRNA levels of uterine hsp70 (Rivera-Gonzalez et al 1998;Tang et al 1995;Wu et al 1996), hsp90, and grp94 (Shyamala et al 1989).…”