CHANGES IN HEAT-SHOCK PROTEIN-90 AND PROTEIN-70 MESSENGER-RIBONUCLEIC-ACID IN UTERINE TISSUES OF THE EWE IN RELATION TO PARTURITION AND REGULATION BY ESTRADIOL AND PROGESTERONE

Steroid receptors, including estrogen receptor (ER) and progesterone r eceptors (PR), form associations with heat shock proteins (Hsps). Diss ociation of Hsps activates PR, whereas retention of Hsp90 in vitro sti mulates ER. Progesterone and estrogen, interacting with their receptor s, regulate myometrial contractility throughout pregnancy and during p arturition. We hypothesize that uterine ER and PR changes concurrent w ith changes in Hsp90 and -70 abundance could alter uterine function. W e quantified changes in Hsp90 and -70 messenger RNA (mRNA) abundance i n pregnant sheep myometrium, endometrium, and fetal placenta during gl ucocorticoid-induced preterm and spontaneous labor. The effects pf est radiol and progesterone on Hsp90 and -70 mRNA in myometrium and endome trium mere examined in ovariectomized nonpregnant ewes. Hsp90 and -70 mRNA distribution was evaluated by in situ hybridization in myometrium and endometrium. Dramatic tissue-specific increases in Hsp90 and 70 m RNA were observed in myometrium and endometrium (P < 0.05) during spon taneous and glucocorticoid-induced labor. Hsp90 and -70 mRNA localized in myometrial, arterial smooth muscle, and endometrial gland epitheli al cells. Estradiol increased Hsp90 and -70 mRNA in myometrium and end ometrium of nonpregnant ewes. Progesterone did not affect Hsp90 and -7 0 mRNA abundance, but inhibited the estradiol-stimulated increase. The se data support our hypothesis that at term, increased abundance of Hs p90 and -70 may inhibit uterine PR and stimulate ER function in uterin e tissues. Similar changes, if present, would be of importance in spec ies showing no progesterone withdrawal before labor, such as primates, including pregnant women.