title: Changes in heat shock protein-90 and -70 messenger ribonucleic acid in uterine tissues of the ewe in relation to parturition and regulation by estradiol and progesterone.
abstract: Steroid receptors, including estrogen receptor (ER) and progesterone receptors (PR), form associations with heat shock proteins (Hsps). Dissociation of Hsps activates PR, whereas retention of Hsp90 in vitro stimulates ER. Progesterone and estrogen, interacting with their receptors, regulate myometrial contractility throughout pregnancy and during parturition. We hypothesize that uterine ER and PR changes concurrent with changes in Hsp90 and -70 abundance could alter uterine function. We quantified changes in Hsp90 and -70 messenger RNA (mRNA) abundance in pregnant sheep myometrium, endometrium, and fetal placenta during glucocorticoid-induced preterm and spontaneous labor. The effects pf estradiol and progesterone on Hsp90 and -70 mRNA in myometrium and endometrium were 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 mRNA were observed in myometrium and endometrium (P < 0.05) during spontaneous and glucocorticoid-induced labor. Hsp90 and -70 mRNA localized in myometrial, arterial smooth muscle, and endometrial gland epithelial cells. Estradiol increased Hsp90 and -70 mRNA in myometrium and endometrium of nonpregnant ewes. Progesterone did not affect Hsp90 and -70 mRNA abundance, but inhibited the estradiol-stimulated increase. These data support our hypothesis that at term, increased abundance of Hsp90 and -70 may inhibit uterine PR and stimulate ER function in uterine tissues. Similar changes, if present, would be of importance in species showing no progesterone withdrawal before labor, such as primates, including pregnant women.
authors.affiliation: Department of Physiology, Cornell University College of Veterinary Medicine, Ithaca, New York 14853-6401, USA.
authors.forename: W X
authors.initials: WX
authors.lastname: Wu
authors.forename: J B
authors.initials: JB
authors.lastname: Derks
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: P W
authors.initials: PW
authors.lastname: Nathanielsz
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics*; D017403:In Situ Hybridization; D007743:Labor, Obstetric / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D012756:Sheep / Q000378:metabolism* / Q000502:physiology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol