title: Progesterone withdrawal, and not increased circulating relaxin, mediates the decrease in myometrial relaxin receptor (RXFP1) expression in late gestation in rats.
abstract: In pregnant rats, a significant decrease in myometrial relaxin family peptide receptor 1 (RXFP1) expression, indicative of a functional relaxin withdrawal for activation of myometrial contractions, occurs in late gestation and during spontaneous labor. This coincides with the highest level of circulating relaxin and a decrease in progesterone. We investigated the potential regulatory role of these two systemic factors on myometrial RXFP1 expression by examining the effects of the antiprogestin RU486 and a monoclonal antibody against rat relaxin (MCA1) in pregnant rats. Rats were injected with RU486 on Gestational Day (GD) 7, 16, or 19 and were killed on GD 8, 17, or 20. RU486 caused a significant reduction in myometrial RXFP1. Plasma progesterone and 17beta-estradiol levels were increased in RU486-treated animals compared with controls. RU486 treatment also caused significant increases in myometrial Esr1 and Vegf and a decrease in Esr2. MCA1 was administered i.v. to rats from GD 17 to GD 19. On GD 20, no significant effect of MCA1 treatment on myometrial RXFP1 expression was observed compared with controls. Furthermore, there was no change in Esr1 or Esr2. A significant reduction in myometrial Vegf, however, was observed. We suggest that blocking progesterone action with RU486 increases plasma 17beta-estradiol and myometrial Esr1 and results in decreased RXFP1 expression. In summary, myometrial RXFP1 expression is mediated mainly by progesterone and not circulating relaxin in pregnant rats.
authors.affiliation: Department of Zoology and Physiology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Lenka A
authors.initials: LA
authors.lastname: Vodstrcil
authors.forename: Oksana
authors.initials: O
authors.lastname: Shynlova
authors.forename: Kerryn
authors.initials: K
authors.lastname: Westcott
authors.forename: Rhianna
authors.initials: R
authors.lastname: Laker
authors.forename: Emma
authors.initials: E
authors.lastname: Simpson
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wlodek
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Parry
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005865:Gestational Age; D006727:Hormone Antagonists / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000097:blood*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D012065:Relaxin / Q000037:antagonists & inhibitors / Q000097:blood; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006727:Hormone Antagonists; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C504789:Rxfp1 protein, rat; D042442:Vascular Endothelial Growth Factors; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D012065:Relaxin