{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:13:37Z","timestamp":1783516417520,"version":"3.55.0"},"reference-count":42,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To search for myometrial candidate genes regulated by progesterone, we isolated annexin 2 cDNA by subtractive hybridization and cloning. We also examined the effect of estradiol and\/or progesterone, individually or combined, on expressions of annexin 2 and its ligand protein, p11 in pregnant sheep intrauterine tissues. Annexin 2 is a Ca2+-dependent phospholipid-binding protein which interacts with p11 to form a bivalent heterotetramer. The heterotetramer was indicated in the production of prostaglandins through the regulation of cytosolic phospholipase A2 (cPLA2) and arachidonic acid release. Thus, annexin 2 and p11 could be the important players in Ca2+ signaling and prostaglandin production in uterine smooth muscles. Twenty-two ewes were treated with vehicle (n = 6), or 5 mg estradiol administered intramuscularly twice a day for 2 days (n = 6), or 100 mg progesterone administered intramuscularly twice a day for 14 days (n = 5), or estradiol plus progesterone with 100 mg progesterone administered intramuscularly twice a day for 10 days (n = 5) and then with vehicle for 2 days followed by estradiol for 2 days (5 mg administered intramuscularly twice a day). At 121 days of gestation age (dGA), endometrium, myometrium, placenta, and cervix were obtained under halothane anesthesia. Subtractive hybridization was used to isolate differentially expressed mRNAs from myometrial tissues treated with progesterone, which was confirmed by western blot at protein level. Annexin 2 and p11 interaction was validated by immunoprecipitation and their expressions in intrauterine tissues were determined by western blot analysis. Data were analyzed by ANOVA. A cDNA clone from myometrial-subtracted library representing differentially expressed mRNA in the pregnant sheep myometrium with progesterone treatment was identified as annexin 2 by sequence analysis and BLASTN search. Annexin 2 was present in both cytosolic and membrane-associated fractions of intrauterine tissues. In contrast, p11 was detectable only in myometrial cytosolic fraction. Both annexin 2 and p11 significantly increased in myometrial cytosolic fraction after progesterone or progesterone plus estradiol treatment. Furthermore, estradiol and progesterone combined had a more profound effect on induction of annexin 2 than progesterone alone. Annexin 2 was immunoprecipitated specifically by p11 antibody from the myometrium. This study indicates that progesterone may play an important role in the control of myometrial contractility by modifying protein expression associated with Ca2+ and prostaglandin signaling systems during pregnancy. Enhanced expression of myometrial annexin 2 in progesterone plus estradiol group supports our hypothesis that estrogen\u2019s stimulation is optimized by progesterone\u2019s priming in the pregnant sheep uterus.<\/jats:p>","DOI":"10.1677\/jme.1.02143","type":"journal-article","created":{"date-parts":[[2007,4,19]],"date-time":"2007-04-19T09:25:17Z","timestamp":1176974717000},"page":"441-454","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":11,"title":["Separate and synergistic effect of progesterone and estradiol on induction of annexin 2 and its interaction protein p11 in pregnant sheep myometrium"],"prefix":"10.1530","volume":"38","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen Xuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2007,2,14]]},"reference":[{"key":"2026070808163884900_AKIBA-ETAL-2000","doi-asserted-by":"crossref","unstructured":"Akiba\n              S\n            \n          , Hatazawa R, Ono K, Hayama M, Matsui H & Sato T 2000 Transforming growth factor-alpha stimulates prostaglandin generation through cytosolic phospholipase A(2) under the control of p11 in rat gastric epithelial cells. British Journal of Pharmacology1311004\u20131010.","DOI":"10.1038\/sj.bjp.0703637"},{"key":"2026070808163884900_BABIYCHUK-AND-DRAEGER-2000","unstructured":"Babiychuk\n              EB\n            \n           & Draeger A 2000 Annexins in cell membrane dynamics. Ca (2+)-regulated association of lipid microdomains. Journal of Cell Biology1501113\u20131124."},{"key":"2026070808163884900_BABIYCHUK-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Babiychuk\n              EB\n            \n          , Palstra RJ, Schaller J, Kampfer U & Draeger A 1999 Annexin VI participates in the formation of a reversible, membrane-cytoskeleton complex in smooth muscle cells. 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Nature Medicine2443\u2013448.","DOI":"10.1038\/nm0496-443"},{"key":"2026070808163884900_OKUSE-ETAL-2002","doi-asserted-by":"crossref","unstructured":"Okuse\n              K\n            \n          , Malik-Hall M, Baker MD, Poon WY, Kong H, Chao MV & Wood JN 2002 Annexin II light chain regulates sensory neuron-specific sodium channel expression. Nature417653\u2013656.","DOI":"10.1038\/nature00781"},{"key":"2026070808163884900_PALLISER-ETAL-2005","unstructured":"Palliser\n              HK\n            \n          , Hirst JJ, Ooi GT, Rice GE, Dellios NL, Escalona RM, Parkington HC & Young IR 2005 Prostaglandin E and F receptor expression and myometrial sensitivity at labor onset in the sheep. 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Endocrinology1384005\u20134012.","DOI":"10.1210\/endo.138.9.5394"},{"key":"2026070808163884900_WU-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Wu\n              WX\n            \n          , Ma XH & Nathanielsz PW 1999 Tissue-specific ontogenic expression of prostaglandin H synthase 2 in the ovine myometrium, endometrium, and placenta during late gestation and at spontaneous term labor. American Journal of Obstetrics and Gynecology1811512\u20131519.","DOI":"10.1016\/S0002-9378(99)70398-4"},{"key":"2026070808163884900_WU-ETAL-2001","doi-asserted-by":"crossref","unstructured":"Wu\n              WX\n            \n          , Ma XH, Zhang Q & Nathanielsz PW 2001 Characterization of topology-, gestation- and labor-related changes of a cassette of myometrial contraction-associated protein mRNA in the pregnant baboon myometrium. 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Journal of Endocrinology182241\u2013248.","DOI":"10.1677\/joe.0.1820241"},{"key":"2026070808163884900_WU-ETAL-2005","unstructured":"Wu\n              WX\n            \n          , Coksaygan T, Chakrabarty K, Collins V, Rose JC & Nathanielsz PW 2005 Sufficient progesterone\u2013priming prior to estradiol-stimulation is required for optimal induction of the cervical prostaglandin system. Biology of Reproduction73343\u2013350."},{"key":"2026070808163884900_YAO-ETAL-1999","doi-asserted-by":"crossref","unstructured":"Yao\n              XL\n            \n          , Cowan MJ, Gladwin MT, Lawrence MM, Angus CW & Shelhamer JH 1999 Dexamethasone alters arachidonate release from human epithelial cells by induction of p11 protein synthesis and inhibition of phospholipase A2 activity. Journal of Biological Chemistry27417202\u201317208.","DOI":"10.1074\/jbc.274.24.17202"},{"key":"2026070808163884900_ZOBIACK-ETAL-2003","doi-asserted-by":"crossref","unstructured":"Zobiack\n              N\n            \n          , Rescher U, Ludwig C, Zeuschner D & Gerke V 2003 The annexin 2\/S100A10 complex controls the distribution of transferrin receptor-containing recycling endosomes. 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