title: Cortisol and interferon tau regulation of endometrial function and conceptus development in female sheep.
abstract: During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1). Ovarian progesterone induces and PG and IFNT stimulates endometrial HSD11B1 expression and keto-reductase activity as well as many epithelial genes that govern trophectoderm proliferation, migration, and attachment during elongation. The primary aim of these studies was to test the hypothesis that HSD11B1-derived cortisol has a biological role in endometrial function and conceptus development during early pregnancy in sheep. In study 1, cyclic ewes received vehicle, cortisol, PF 915275 (PF; a selective inhibitor of HSD11B1), cortisol and PF, meloxicam (a selective inhibitor of PTGS2), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus. Cortisol and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium. Some effects of cortisol and IFNT were mediated by PTGS2-derived PG. In study 2, bred ewes received PF 915275 or recombinant ovine IFNT and into the uterus from day 10 to day 14 after mating. Inhibition of HSD11B1 activity in utero prevented conceptus elongation, whereas IFNT rescued conceptus elongation in PF-infused ewes. These results suggest that HSD11B1-derived cortisol mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep.
authors.affiliation: Center for Reproductive Biology, Washington State University, Pullman, WA 99164-6353, USA.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dorniak
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Welsh
authors.forename: Fuller W
authors.initials: FW
authors.lastname: Bazer
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Spencer
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006854:Hydrocortisone / Q000502:physiology*; D007370:Interferon Type I / Q000494:pharmacology / Q000502:physiology*; D000077239:Meloxicam; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology / Q000502:physiology*; D034561:Sheep, Domestic; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: C525872:4'-cyanobiphenyl-4-sulfonic acid (6-aminopyridin-2-yl)amide; D000631:Aminopyridines; D007370:Interferon Type I; D011257:Pregnancy Proteins; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; C020947:interferon tau; D042842:11-beta-Hydroxysteroid Dehydrogenases; D051546:Cyclooxygenase 2; D000077239:Meloxicam; D006854:Hydrocortisone