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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2013

Open Access 01-12-2013 | Research

The classical progesterone receptor mediates the rapid reduction of fallopian tube ciliary beat frequency by progesterone

Authors: Anna Bylander, Karin Lind, Mattias Goksör, Håkan Billig, DG Joakim Larsson

Published in: Reproductive Biology and Endocrinology | Issue 1/2013

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Abstract

Background

The transport of gametes as well as the zygote is facilitated by motile cilia lining the inside of the fallopian tube. Progesterone reduces the ciliary beat frequency within 30 minutes in both cows and mice. This rapid reduction suggest the involvement of a non-genomic signaling mechanism, although it is not known which receptors that are involved. Here we investigated the possible involvement of the classical progesterone receptor in this process.

Method

The ciliary beat frequency of mice fallopian tube was measured ex vivo using an inverted bright field microscope and a high speed camera. The effects of the agonists progesterone and promegestone and an antagonist, mifeprestone, were investigated in wildtype mice. The effect of progesterone was also investigated in mice lacking the classical progesterone receptor.

Results

Progesterone, as well as the more specific PR agonist promegestone, significantly reduced the CBF at concentrations of 10–100 nanomolar within 10–30 minutes. In the absence of progesterone, the PR antagonist mifeprestone had no effect on the ciliary beat frequency at a concentration of 1 micromolar. When ciliated cells were pre-incubated with 1 micromolar mifeprestone, addition of progesterone did not reduce the ciliary beat frequency. Accordingly, in ciliated cells from mice not expressing the classical progesterone receptor, exposure to 100 nanomolar progesterone did not reduce the ciliary beat frequency.

Conclusions

This is the first study to provide comprehensive evidence that the classical progesterone receptor mediates the rapid reduction of the tubal ciliary beat frequency by progesterone.
Appendix
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Literature
1.
Spilman CH, Harper MJ: Effects of prostaglandins on oviductal motility and egg transport. Gynecol Invest. 1975, 6: 186-205. 10.1159/000301516.CrossRefPubMed
2.
Croxatto HB: Physiology of gamete and embryo transport through the fallopian tube. Reprod Biomed Online. 2002, 4: 160-169. 10.1016/S1472-6483(10)61935-9.CrossRefPubMed
3.
Lyons RA, Saridogan E, Djahanbakhch O: The reproductive significance of human Fallopian tube cilia. Hum Reprod Update. 2006, 12: 363-372. 10.1093/humupd/dml012.CrossRefPubMed
4.
Halbert SA, Becker DR, Szal SE: Ovum transport in the rat oviductal ampulla in the absence of muscle contractility. Biol Reprod. 1989, 40: 1131-1136. 10.1095/biolreprod40.6.1131.CrossRefPubMed
5.
Halbert SA, Tam PY, Blandau RJ: Egg transport in the rabbit oviduct: the roles of cilia and muscle. Science. 1976, 191: 1052-1053. 10.1126/science.1251215.CrossRefPubMed
6.
Mahmood T, Saridogan E, Smutna S, Habib AM, Djahanbakhch O: The effect of ovarian steroids on epithelial ciliary beat frequency in the human Fallopian tube. Hum Reprod. 1998, 13: 2991-2994. 10.1093/humrep/13.11.2991.CrossRefPubMed
7.
Wessel T, Schuchter U, Walt H: Ciliary motility in bovine oviducts for sensing rapid non-genomic reactions upon exposure to progesterone. Horm Metab Res. 2004, 36: 136-141.CrossRefPubMed
8.
Nakahari T, Nishimura A, Shimamoto C, Sakai A, Kuwabara H, Nakano T, Tanaka S, Kohda Y, Matsumura H, Mori H: The regulation of ciliary beat frequency by ovarian steroids in the guinea pig Fallopian tube: interactions between oestradiol and progesterone. Biomed Res. 2011, 32: 321-328. 10.2220/biomedres.32.321.CrossRefPubMed
9.
Bylander A, Nutu M, Wellander R, Goksör M, Billig H, Larsson DGJ: Rapid effects of progesterone on ciliary beat frequency in the mouse fallopian tube. Reprod Biol Endocrinol. 2010, 8: 48-10.1186/1477-7827-8-48.PubMedCentralCrossRefPubMed
10.
Walmer DK, Wrona MA, Hughes CL, Nelson KG: Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: correlation with circulating estradiol and progesterone. Endocrinol. 1992, 131: 1458-1466. 10.1210/en.131.3.1458.
11.
Nutu M, Weijdegård B, Thomas P, Bergh C, Thurin-Kjellberg A, Pang Y, Billig H, Larsson DGJ: Membrane progesterone receptor gamma: tissue distribution and expression in ciliated cells in the fallopian tube. Mol Reprod Dev. 2007, 74: 843-850. 10.1002/mrd.20685.CrossRefPubMed
12.
Nutu M, Weijdegård B, Thomas P, Thurin-Kjellberg A, Billig H, Larsson DGJ: Distribution and hormonal regulation of membrane progesterone receptors beta and gamma in ciliated epithelial cells of mouse and human fallopian tubes. Reprod Biol Endocrinol. 2009, 7: 89-10.1186/1477-7827-7-89.PubMedCentralCrossRefPubMed
13.
Teilmann SC, Clement CA, Thorup J, Byskov AG, Christensen ST: Expression and localization of the progesterone receptor in mouse and human reproductive organs. J Endocrinol. 2006, 191: 525-535. 10.1677/joe.1.06565.CrossRefPubMed
14.
Zhu Y, Hanna RN, Schaaf MJ, Spaink HP, Thomas P: Candidates for membrane progestin receptors-Past approaches and future challenges. Comp Biochem Physiol C Toxicol Pharmacol. 2008, 148: 381-389. 10.1016/j.cbpc.2008.05.019.CrossRefPubMed
15.
Zhu Y, Bond J, Thomas P: Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. PNAS. 2003, 100: 2237-2242. 10.1073/pnas.0436133100.PubMedCentralCrossRefPubMed
16.
Zhu Y, Rice CD, Pang Y, Pace M, Thomas P: Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. PNAS. 2003, 100: 2231-2236. 10.1073/pnas.0336132100.PubMedCentralCrossRefPubMed
17.
Pace MC, Thomas P: Activation of a pertussis toxin-sensitive, inhibitory G-protein is necessary for steroid-mediated oocyte maturation in spotted seatrout. Dev Biol. 2005, 285: 70-79. 10.1016/j.ydbio.2005.06.003.CrossRefPubMed
18.
Qiu HB, Lu SS, Ji KL, Song XM, Lu YQ, Zhang M, Lu KH: Membrane progestin receptor beta (mPR-beta): a protein related to cumulus expansion that is involved in in vitro maturation of pig cumulus-oocyte complexes. Steroids. 2008, 73: 1416-1423. 10.1016/j.steroids.2008.07.007.CrossRefPubMed
19.
Tubbs C, Thomas P: Progestin signaling through an olfactory G protein and membrane progestin receptor alpha in Atlantic croaker sperm: potential role in induction of sperm hypermotility. Endocrinol. 2008, 150: 473-484. 10.1210/en.2008-0512.CrossRef
20.
Bayaa M, Booth RA, Sheng Y, Liu XJ: The classical progesterone receptor mediates Xenopus oocyte maturation through a nongenomic mechanism. Proc Natl Acad Sci U S A. 2000, 97: 12607-12612. 10.1073/pnas.220302597.PubMedCentralCrossRefPubMed
21.
Tian J, Kim S, Heilig E, Ruderman JV: Identification of XPR-1, a progesterone receptor required for Xenopus oocyte activation. Proc Natl Acad Sci U S A. 2000, 97: 14358-14363. 10.1073/pnas.250492197.PubMedCentralCrossRefPubMed
22.
Faivre E, Skildum A, Pierson-Mullany L, Lange CA: Integration of progesterone receptor mediated rapid signaling and nuclear actions in breast cancer cell models: role of mitogen-activated protein kinases and cell cycle regulators. Steroids. 2005, 70: 418-426. 10.1016/j.steroids.2005.02.012.CrossRefPubMed
23.
Boonyaratanakornkit V, McGowan E, Sherman L, Mancini MA, Cheskis BJ, Edwards DP: The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Mol Endocrinol. 2007, 21: 359-375.CrossRefPubMed
24.
Boonyaratanakornkit V, Scott MP, Ribon V, Sherman L, Anderson SM, Maller JL, Miller WT, Edwards DP: Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases. Mol Cell. 2001, 8: 269-280. 10.1016/S1097-2765(01)00304-5.CrossRefPubMed
25.
Boonyaratanakornkit V, Bi Y, Rudd M, Edwards DP: The role and mechanism of progesterone receptor activation of extra-nuclear signaling pathways in regulating gene transcription and cell cycle progression. Steroids. 2008, 73: 922-928. 10.1016/j.steroids.2008.01.010.CrossRefPubMed
26.
Boonyaratanakornkit V, Edwards DP: Receptor mechanisms mediating non-genomic actions of sex steroids. Semin Reprod Med. 2007, 25: 139-153. 10.1055/s-2007-973427.CrossRefPubMed
27.
Mastroianni L: The fallopian tube and reproductive health. J Pediatr Adolesc Gynecol. 1999, 12: 121-126. 10.1016/S1038-3188(99)00003-0.CrossRefPubMed
28.
Halbert SA, Patton DL, Zarutskie PW, Soules MR: Function and structure of cilia in the fallopian tube of an infertile woman with Kartagener's syndrome. Hum Reprod. 1997, 12: 55-58. 10.1093/humrep/12.1.55.CrossRefPubMed
29.
Leng Z, Moore DE, Mueller BA, Critchlow CW, Patton DL, Halbert SA, Wang SP: Characterization of ciliary activity in distal Fallopian tube biopsies of women with obstructive tubal infertility. Hum Reprod. 1998, 13: 3121-3127. 10.1093/humrep/13.11.3121.CrossRefPubMed
30.
Paltieli Y, Eibschitz I, Ziskind G, Ohel G, Silbermann M, Weichselbaum A: High progesterone levels and ciliary dysfunction–a possible cause of ectopic pregnancy. J Assist Reprod Genet. 2000, 17: 103-106. 10.1023/A:1009465900824.PubMedCentralCrossRefPubMed
31.
Shao R: Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models. Hum Reprod. 2010, 25: 584-587. 10.1093/humrep/dep438.PubMedCentralCrossRefPubMed
32.
Ismail PM, Li J, DeMayo FJ, O'Malley BW, Lydon JP: A novel LacZ reporter mouse reveals complex regulation of the progesterone receptor promoter during mammary gland development. Mol Endocrinol. 2002, 16: 2475-2489. 10.1210/me.2002-0169.CrossRefPubMed
33.
Pang Y, Thomas P: Progesterone signals through membrane progesterone receptors (mPRs) in MDA-MB-468 and mPR-transfected MDA-MB-231 breast cancer cells which lack full-length and N-terminally truncated isoforms of the nuclear progesterone receptor. Steroids. 2011, 76: 921-928.PubMedCentralPubMed
34.
Dressing GE, Alyea R, Pang Y, Thomas P: Membrane progesterone receptors (mPRs) mediate progestin induced antimorbidity in breast cancer cells and are expressed in human breast tumors. Horm Cancer. 2012, 3: 101-112. 10.1007/s12672-012-0106-x.CrossRefPubMed
35.
Kelder J, Azevedo R, Pang Y, de Vlieg J, Dong J, Thomas P: Comparison between steroid binding to membrane progesterone receptor alpha (mPRalpha) and to nuclear progesterone receptor: correlation with physicochemical properties assessed by comparative molecular field analysis and identification of mPRalpha-specific agonists. Steroids. 2010, 75: 314-322. 10.1016/j.steroids.2010.01.010.PubMedCentralCrossRefPubMed
36.
Lyons RA, Saridogan E, Djahanbakhch O: The effect of ovarian follicular fluid and peritoneal fluid on Fallopian tube ciliary beat frequency. Hum Reprod. 2006, 21: 52-56.CrossRefPubMed
37.
Falkenstein E, Norman AW, Wehling M: Mannheim classification of nongenomically initiated (rapid) steroid action(s). J Clin Endocrinol Metab. 2000, 85: 2072-2075. 10.1210/jc.85.5.2072.CrossRefPubMed
38.
Wehling M: Specific, nongenomic actions of steroid hormones. Annu Rev Physiol. 1997, 59: 365-393. 10.1146/annurev.physiol.59.1.365.CrossRefPubMed
39.
Shivaji S, Jagannadham MV: Steroid-induced perturbations of membranes and its relevance to sperm acrosome reaction. Biochim Biophys Acta. 1992, 1108: 99-109. 10.1016/0005-2736(92)90119-7.CrossRefPubMed
40.
Heimler I, Rawlins RG, Binor Z, Aiman J, Raff H, Hutz RJ: Elevated follicular fluid angiotensin II and pregnancy outcome. Fertil Steril. 1995, 63: 528-534.PubMed
41.
Koninckx PR, Heyns W, Verhoeven G, Van Baelen H, Lissens WD, De Moor P, Brosens IA: Biochemical characterization of peritoneal fluid in women during the menstrual cycle. J Clin Endocrinol Metab. 1980, 51: 1239-1244. 10.1210/jcem-51-6-1239.CrossRefPubMed
42.
Jain R, Ray JM, Pan JH, Brody SL: Sex hormone-dependent regulation of cilia beat frequency in airway epithelium. Am J Respir Cell Mol Biol. 2012, 46: 446-453. 10.1165/rcmb.2011-0107OC.PubMedCentralCrossRefPubMed
43.
Shao R, Weijdegård B, Ljungström K, Friberg A, Zhu C, Wang X, Zhu Y, Fernandez-Rodriguez J, Egecioglu E, Rung E, Billig H: Nuclear progesterone receptor A and B isoforms in mouse fallopian tube and uterus: implications for expression, regulation, and cellular function. Am J Physiol Endocrinol Metab. 2006, 291: E59-E72. 10.1152/ajpendo.00582.2005.CrossRefPubMed
44.
Pereira PP, Cabar FR, Raiza LC, Roncaglia MT, Zugaib M: Emergency contraception and ectopic pregnancy: report of 2 cases. Clinics (Sao Paulo). 2005, 60: 497-500.CrossRef
Metadata
Title
The classical progesterone receptor mediates the rapid reduction of fallopian tube ciliary beat frequency by progesterone
Authors
Anna Bylander
Karin Lind
Mattias Goksör
Håkan Billig
DG Joakim Larsson
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2013
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-11-33

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