Schematic illustrating hormonal regulation of the endometrial luteolytic mechanism and antiluteolytic effects of the conceptus on the endometrium in the ovine uterus. During estrus and metestrus, oxytocin receptors (OTR) are present on the uterine lumenal epithelium (LE) and superficial ductal glandular epithelium (sGE), because estrogen (E) levels are high and increase expression of estrogen receptor alpha (ERα) and OTR. The progesterone receptor (PR) is present, but low systemic levels of progesterone result in insufficient numbers of activated PR to suppress ERα and OTR synthesis. During early diestrus, endometrial ERα and estrogen are low, but progesterone levels begin to increase with formation of the CL. Progesterone acts through the PR to suppress ERα and OTR synthesis for 8 to 10 days. Continuous exposure of the endometrium to progesterone eventually down-regulates PR gene expression in the endometrial luminal epithelium (LE) by Days 11 to 12 of the estrous cycle. The loss of PR terminates the progesterone block to ERα and OTR formation. Thus, ERα appears on Days 11 to 12 post-estrus, which is closely followed by OTR on Days 13 and 14. The increase in OTR expression is facilitated by increasing secretion of estrogen by ovarian follicles. In both cyclic and pregnant sheep, oxytocin (OT) is released from the posterior pituitary and corpus luteum beginning on Day 9. In cyclic sheep, OT binds to OTR on the endometrial epithelium and increases release of luteolytic pulses of prostaglandin F2α (PGF2α) to regress the CL through a COX-2 pathway. In pregnant sheep, inteferon tau (IFNτ) is synthesized and secreted by the elongating conceptus beginning on Day 10 of pregnancy. IFNτ binds to Type I IFN receptors (IFNAR) on the endometrial LE and inhibits transcription of the ERα gene through a signaling pathway involving IFN regulatory factor 2 (IRF-2). These actions of IFNτ on the ERα gene prevent OTR formation, thereby maintaining the CL and progesterone production. Legend: E, estrogen; ERα, estrogen receptor alpha; IFNτ, interferon tau; IRF-2, interferon regulatory factor two; OT, oxytocin; OTR, oxytocin receptor; P, progesterone; PGF2α, prostaglandin F2 alpha; PR, progesterone receptor.