title: The progesterone receptor antagonist, onapristone has differential effects on the timing and control of the luteolytic mechanism depending on timing of administration in sheep.
abstract: Cyclic ewes were treated with control vehicle or progesterone receptor antagonist (onapristone; 100mg i.m. twice daily) during either early (day 3-5) or late (day 12-14) luteal phase and plasma samples collected for hormone analysis and to determine endogenous and oxytocin induced PGF2α release. On day 14 and 17, ewes were euthanised and reproductive tracts collected for ovarian morphology and endometrium for oxytoxin and steroid hormone receptor analysis. Early treatment increased LH, but not progesterone or oestradiol, while late treatment elevated all three hormones. Early treatment delayed the up-regulation of endometrial oxytocin receptors and responsiveness to oxytocin challenge, delaying luteolysis. Late treatment advanced development of oxytocin receptors and responsiveness to oxytocin though not timing of luteolysis. Patterns of hormone receptor mRNA were differentially disrupted by treatments. Results provide mechanistic insight into hormonal control of the oestrous cycle and identify the ability of the luteolytic mechanism to dissociate from functional luteolysis.
authors.affiliation: University of Nottingham, School of Biosciences, Division of Animal Sciences, Sutton Bonington Campus, Loughborough LE12 5RD, UK. george.mann@nottingham.ac.uk
authors.forename: G E
authors.initials: GE
authors.lastname: Mann
authors.forename: D C
authors.initials: DC
authors.lastname: Wathes
authors.forename: R S
authors.initials: RS
authors.lastname: Robinson
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000097:blood / Q000378:metabolism; D004334:Drug Administration Schedule; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004958:Estradiol / Q000096:biosynthesis; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D006067:Gonanes / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000096:biosynthesis; D003341:Luteolysis / Q000187:drug effects* / Q000502:physiology; D010121:Oxytocin / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis; D018045:Receptors, Oxytocin / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D012756:Sheep; D034561:Sheep, Domestic; D013997:Time Factors
chemical_list: D005300:Fertility Agents, Female; D006067:Gonanes; D018045:Receptors, Oxytocin; D011980:Receptors, Progesterone; D011374:Progesterone; D004958:Estradiol; D010121:Oxytocin; D007986:Luteinizing Hormone; D015237:Dinoprost; C053238:onapristone
keywords: Luteolysis; Oestrous cycle; Progesterone antagonist; Sheep