The progesterone receptor antagonist, onapristone has differential effects on the timing and control of the luteolytic mechanism depending on timing of administration in sheep

Mann, G.E.; Wathes, D.C.; Robinson, R.S.

Abstract

Cyclic ewes were treated with control vehicle or progesterone receptor antagonist (onapristone; 100 mg 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.

Citation

Mann, G., Wathes, D., & Robinson, R. (2013). The progesterone receptor antagonist, onapristone has differential effects on the timing and control of the luteolytic mechanism depending on timing of administration in sheep. Molecular and Cellular Endocrinology, 376(1-2), 1-11. https://doi.org/10.1016/j.mce.2013.06.001

• Journal Article Type: Article
• Acceptance Date: Jun 2, 2013
• Online Publication Date: Jun 7, 2013
• Publication Date: 2013-08
• Deposit Date: Mar 29, 2019
• Journal: Molecular and Cellular Endocrinology
• Print ISSN: 0303-7207
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 376
• Issue: 1-2
• Pages: 1-11
• DOI: https://doi.org/10.1016/j.mce.2013.06.001
• Public URL: https://nottingham-repository.worktribe.com/output/1708768
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0303720713002396
• Additional Information: This article is maintained by: Elsevier; Article 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; Journal Title: Molecular and Cellular Endocrinology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.mce.2013.06.001; Content Type: article; Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.