{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:07:51Z","timestamp":1773421671830,"version":"3.50.1"},"reference-count":69,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,5,11]],"date-time":"2005-05-11T00:00:00Z","timestamp":1115769600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:p>Pregnancy and the follicular phase are physiological states of elevated oestrogen levels and rises in uterine blood flow (UBF). The dramatic increase in utero\u2010placental blood flow during gestation is required for normal fetal growth and development. Oestrogen exerts its vasodilatory effect by binding to its specific oestrogen receptors (ER) in target cells, resulting in increased expression and activity of endothelial nitric oxide synthase (eNOS) to relax vascular smooth muscle (VSM). However, the regulation of endothelial <jats:italic>versus<\/jats:italic> VSM ER\u03b1 and ER\u03b2 expression in uterine arteries (UAs) during the ovarian cycle, pregnancy and with exogenous hormone replacement therapy (HRT) are currently unknown. ER mRNA and protein localization was determined by <jats:italic>in situ<\/jats:italic> hybridization (ISH) using <jats:sup>35<\/jats:sup>S\u2010labelled riboprobes and immunohistochemistry (IHC), respectively. UA endothelial (UAendo), UA VSM, omental artery endothelium (OA endo), and OA VSM proteins were isolated and ER\u03b1 and ER\u03b2 protein expression was determined by Western analysis. We observed by ISH and IHC that ER\u03b1 and ER\u03b2 mRNA and protein were localized in both UAendo and UA VSM. Immunoblot data demonstrated ovarian hormone specific regulation of ER\u03b1 and ER\u03b2 protein in UAendo and UA VSM. Compared to luteal phase sheep, both ER\u03b1 and ER\u03b2 levels in UAendo were elevated in follicular phase sheep. Whereas ER\u03b2 was elevated by pregnancy in UAendo and UA VSM, ER\u03b1 was not appreciably altered. eNOS was increased in UAendo from follicular and pregnant sheep. Ovariectomized ewes (OVEX) had substantially reduced UAendo ER\u03b2, but not UAendo ER\u03b1 or OAendo ER\u03b1 and ER\u03b2. In contrast, OVEX increased UA VSM ER\u03b1 and ER\u03b2 and decreased OA VSM ER\u03b1 and ER\u03b2. Treatment with oestradiol\u201017\u03b2 (E2\u03b2), but not progesterone or their combination, increased UAendo ER\u03b1 levels. The reduced ER\u03b2 in UAendo from OVEX ewes was reversed by E<jats:sub>2<\/jats:sub>\u03b2 and progesterone treatment. While ER\u03b1 and eNOS were not elevated in any other reproductive or non\u2010reproductive endothelia tested, ER\u03b2 was augmented by pregnancy in uterine, mammary, placenta, and coronary artery endothelia. ER\u03b1 and ER\u03b2 mRNA and protein are expressed in UA endothelium with expression levels depending on the endocrine status of the animal, indicating UA endothelium is a target for oestrogen action <jats:italic>in vivo,<\/jats:italic> and that the two receptors appear to be differentially regulated in a spatial and temporal fashion with regard to the reproductive status or HRT.<\/jats:p>","DOI":"10.1113\/jphysiol.2005.085753","type":"journal-article","created":{"date-parts":[[2005,3,18]],"date-time":"2005-03-18T04:47:48Z","timestamp":1111121268000},"page":"85-99","source":"Crossref","is-referenced-by-count":57,"title":["Endothelial vasodilator production by ovine uterine and systemic arteries: ovarian steroid and pregnancy control of ER\u03b1 and ER\u03b2 levels"],"prefix":"10.1113","volume":"565","author":[{"given":"Michael J.","family":"Byers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Zangl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terrance M.","family":"Phernetton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gladys","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong\u2010bao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald R.","family":"Magness","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,5,11]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(16)33239-2"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1690241"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000298810"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.11.2.172"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118774"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.16.5.938"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0547"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(94)90102-3"},{"key":"e_1_2_5_10_1","first-page":"2172","volume-title":"Heart Disease: A Textbook of Cardiovascular Medicine","author":"Elkayam U","year":"2001"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod21.3.617"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod27.4.878"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(84)90241-3"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.103.019901"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(86)90035-X"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(69)90560-2"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(16)34033-9"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2004.06.094"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.15.1792"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.89.5.1943"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1801.097239"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-93-2-478"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.6.1402"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/15.6.2499"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.138.3.863"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5925"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(00)00266-5"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(83)90439-8"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.035949"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.2.224"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.89.4.1501"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-1804-3_18"},{"key":"e_1_2_5_33_1","first-page":"E690","article-title":"Systemic and uterine responses to chronic infusion of estradiol\u201017beta","volume":"265","author":"Magness RR","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.086439"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.3.H731"},{"key":"e_1_2_5_36_1","first-page":"239","volume-title":"Reproductive and Perinatal Medicine, vol. 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