Abstract
Objective
To assess relative expression levels of mRNA for EP3 isoforms EP3-2, EP3-3, and EP3-6 in human myometrium in various physiologic states.
Methods
Using semiquantitative reverse transcriptase-polymerase chain reaction, we analyzed myometrial samples from 46 women (ten menopausal, ten nongravid premenopausal, 19 gravidas, seven premenopausal misoprostol-treated nongravid women) for the specific expression of mRNA messages for the EP3 receptor isoforms EP3-2, EP3-3, and EP3-6.
Results
We found that the expression of EP3-2 was significantly lower in gravid than nongravid myometrium (P < .0001). Levels of the EP3-6 message were higher in gravid samples than in nongravid specimens (P < .02). EP3-3 mRNA was present in higher levels in menopausal samples compared with the other groups.
Conclusions
The selective fluctuation of mRNA expression of the different EP3 isoforms suggests the possibility of an important regulatory role for these receptors in myometrial contractility. Additional studies are necessary to evaluate the exact mechanism of action of EP3 receptor isoforms in human myometrium.
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References
Olson DM, Mijovic JE, Sadowsky DW. Control of human parturition. Semin Perinatol 1995;19:52–63.
Cibils LA. Contractility of the nonpregnant human uterus. Obstet Gynecol 1967;30:441–461.
Akerlund M. Pathophysiology of dysmenorrhea. Acta Obstet Gynecol Scand 1979;87(Suppl):27–32.
Maggi M, Baldi E, Susini T. Hormonal and local regulation of uterine activity during parturition: Part 11—The prostaglandin and adrenergic systems. J Endocrinol Invest 1994;17:757–770.
Goharkhay N, Stanczyk FZ, Gentzschein E, Wing DA. Plasma prostaglandin E2 metabolite levels during labor induction with a sustained-release prostaglandin E2 vaginal insert. J Soc Gynecol Investig 2000;7:338–342.
Russell JA, Leng G. Sex, parturition and motherhood without oxytocin? J Endocrinol 1998;157:343–359.
Helmer H, Hackl T, Schneeberger C, et al. Oxytocin and vasopressin 1a receptor gene expression in the cycling or pregnant human uterus. Am J Obstet Gynecol 1998;179:1572–1578.
Goharkhay N, Felix JC, Naidu V, Hanna M, Kovacs BW, Wing DA. Expression or the Oxytocin receptor (OTR) and the vasopressin V1aR receptor in human myometrium. J Soc Gynecol Investig 2001;8(Suppl):126–7A–126–7A.
Brodt-Eppley J, Myatt L. Prostaglandin receptors in lower segment myometrium during gestation and labor. Obstet Gynecol 1999;93:890–893.
Kotani M, Tanaka I, Ogawa Y, et al. Structural organization of the human prostaglandin EP3 receptor subtype gene (PTGER3). Genomics 1997;40:425–434.
Kotani M, Tanaka I, Ogawa Y, et al. Molecular cloning and expression of multiple isoforms of human prostaglandin E receptor EP3 subtype generated by alternative messenger RNA splicing: Multiple second messenger systems and tissue-specific distribution. Mol Pharmacol 1995;48:869–879.
Regan JW, Bailey TJ, Donello JE, et al. Molecular cloning and expression of human EP3 receptors: Evidence of three variants with differing carboxyl termini. Br J Pharmacol 1994;112:377–385.
Adam M, Boie Y, Rushmore TH, et al. Cloning and expression of three isoforms of the human EP3 prostanoid receptor. FEBS Lett 1994;338:170–174.
Schmid A, Thierauch KH, Schleuning WD, Dinter H. Splice variants of the human EP3 receptor for prostaglandin E2. Eur J Biochem 1995;228:23–30.
Molnar M, Hertelendy F. PGF2 alpha and PGE2 binding to rat myometrium during gestation, parturition, and postpartum. Am J Physiol 1990;258:E740–E747.
Ma X, Wu WX, Nathanielsz PW. Differential regulation of prostaglandin EP and FP receptors in pregnant sheep myometrium and endometrium during spontaneous term labor. Biol Reprod 1999;61:1281–1286.
Brodt-Eppley J, Myatt L. Changes in expression of contractile FP and relaxatory EP2 receptors in pregnant rat myometrium during late gestation, at labor, and postpartum. Biol Reprod 1998;59:878–883.
Dong YL, Yallampalli C. Pregnancy and exogenous steroid treatments modulate the expression of relaxant EP(2) and contractile FP receptors in the rat uterus. Biol Reprod 2000;62:533–539.
Matsumoto T, Sagawa N, Yoshida M, et al. The prostaglandin E2 and F2 alpha-receptor genes are expressed in human myometrium and are down regulated during pregnancy. Biochem Biophys Res Commun 1997;238:838–841.
Rozen S, Skaletsky H. Primer3. Copy available at http://www.genome.wi.mit.edu/genome-software/other/primer3.html.
Nickoloff BJ, Naidu Y. Perturbation of epidermal barrier function correlates with initiation of cytokine cascade in human skin. J Am Acad Dermatol 1994;30:535–546.
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Funded by the Departments of Obstetrics and Gynecology and Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California.
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Wing, D.A., Goharkhay, N., Hanna, M. et al. EP3-2 Receptor mRNA Expression Is Reduced and EP3-6 Receptor mRNA Expression Is Increased in Gravid Human Myometrium. Reprod. Sci. 10, 124–129 (2003). https://doi.org/10.1016/S1071-5576(03)00007-8
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DOI: https://doi.org/10.1016/S1071-5576(03)00007-8