{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:23:28Z","timestamp":1777940608893,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      In Graves' orbitopathy (GO), increased proliferation, excess adipogenesis, and hyaluronan overproduction produce GO exophthalmos. Enophthalmos occurs in some glaucoma patients treated with Bimatoprost (prostaglandin F\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      , PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      ) eye drops. We hypothesized that enophthalmos is secondary to reductions in orbital tissue proliferation, adipogenesis, and\/or increased lipolysis. We aimed to determine which of these is affected by PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      by using the 3T3-L1 murine preadipocyte cell line and primary human orbital fibroblasts (OFs) from GO patients (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =5) and non-GO (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =5).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      3T3-L1 cells and orbital OFs were cultured alone or with PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      (all experiments used 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      to 10\n                      <jats:sup>\u22126<\/jats:sup>\n                      M) and counted on days 1\/2\/3 or 5, respectively; cell cycle analysis (flow cytometry) was applied. Adipogenesis (in the presence\/absence of PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      ) was evaluated (day 7 or 15 for 3T3-L1 and primary cells, respectively) morphologically by Oil Red O staining and quantitative polymerase chain reaction measurement of adipogenesis markers (glycerol-3-phosphate dehydrogenase and lipoprotein lipase, respectively). For lipolysis,\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      \u2013differentiated 3T3-L1 or mature orbital adipocytes were incubated with norepinephrine and PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      and free glycerol was assayed. Appropriate statistical tests were applied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The population doubling time of 3T3-L1 was 27.3\u00b11.4 hours\u2014significantly increased by dimethyl sulfoxide 0.02% to 44.6\u00b14.8 hours (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.007) and further significantly increased (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.049 compared with dimethyl sulfoxide) by 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      M PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      to 93.6\u00b119.0 hours, indicating reduced proliferation, which was caused by prolongation of G2\/M. GO OFs proliferated significantly more rapidly than non-GO (population doubling time 5.36\u00b10.34 or 6.63\u00b10.35 days, respectively,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      =0.035), but the proliferation of both was significantly reduced (dose dependent from 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      M) by PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      , again with prolongation of G2\/M. Adipogenesis in 3T3-L1 cells was minimally affected by PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      when assessed morphologically, but the drug significantly reduced transcripts of the glycerol-3-phosphate dehydrogenase differentiation marker. GO OFs displayed significantly higher adipogenic potential than non-GO, but in both populations, adipogenesis, evaluated by all 3 methods, was significantly reduced (dose dependent from 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      M) by PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      . There was no effect of PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      on basal or norepinephrine-induced lipolysis, in 3T3-L1 or human OFs, either GO or non-GO.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      The results demonstrate that PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      significantly reduces proliferation and adipogenesis and that human OFs are more sensitive to its effects than 3T3-L1. Consequently, PGF\n                      <jats:sub>2\u03b1<\/jats:sub>\n                      could be effective in the treatment of GO.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2013.0194","type":"journal-article","created":{"date-parts":[[2013,9,3]],"date-time":"2013-09-03T09:55:46Z","timestamp":1378202146000},"page":"1600-1608","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":23,"title":["Effects of Prostaglandin F\n                    <sub>2\u03b1<\/sub>\n                    on Adipocyte Biology Relevant to Graves' Orbitopathy"],"prefix":"10.1177","volume":"23","author":[{"given":"Mohd Shazli","family":"Draman","sequence":"first","affiliation":[{"name":"Cardiff University","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Grennan-Jones","sequence":"additional","affiliation":[{"name":"Cardiff University","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiff University","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter N","family":"Taylor","sequence":"additional","affiliation":[{"name":"Cardiff University","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommy Kyaw","family":"Tun","sequence":"additional","affiliation":[{"name":"Royal College of Surgeons in Ireland","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"McDermott","sequence":"additional","affiliation":[{"name":"Royal College of Surgeons in Ireland","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Moriarty","sequence":"additional","affiliation":[{"name":"Royal Victoria Eye & Ear Hospital","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Morris","sequence":"additional","affiliation":[{"name":"University Hospital of Wales","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Lane","sequence":"additional","affiliation":[{"name":"University Hospital of Wales","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seamus","family":"Sreenan","sequence":"additional","affiliation":[{"name":"Royal College of Surgeons in Ireland","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Dayan","sequence":"additional","affiliation":[{"name":"Cardiff University","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Ludgate","sequence":"additional","affiliation":[{"name":"Cardiff University","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2013,12,1]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(02)00327-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.opx.0000141791.16683.4a"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/IOP.0b013e31817d81df"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1027362"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2009.0019"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3109\/15569521003796860"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10384-010-0904-z"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3109\/01676830.2010.527028"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6433"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(89)90478-4"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)41991-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42265-4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2660661"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041550206"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21044"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207913200"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1440311"},{"key":"e_1_3_2_19_2","first-page":"168","article-title":"Management of Graves' ophthalmopathy: reality and perspectives","volume":"21","author":"Bartalena L","year":"2000","unstructured":"Bartalena L, , Pinchera A, , Marcocci C. 2000. Management of Graves' ophthalmopathy: reality and perspectives. Endocr Rev, 21:168\u2013199.","journal-title":"Endocr Rev"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.003616"},{"key":"e_1_3_2_21_2","first-page":"477","article-title":"The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota","volume":"92","author":"Bartley GB","year":"1994","unstructured":"Bartley GB. 1994. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc, 92:477\u2013588.","journal-title":"Trans Am Ophthalmol Soc"},{"key":"e_1_3_2_22_2","first-page":"651","article-title":"Ophthalmopathy of Graves' disease: computerized volume measurements of the orbital fat and muscle","volume":"7","author":"Forbes G","year":"1986","unstructured":"Forbes G, , Gorman CA, , Brennan MD, , Gehring DG, , Ilstrup DM, , Earnest Ft. 1986. Ophthalmopathy of Graves' disease: computerized volume measurements of the orbital fat and muscle. Am J Neuroradiol, 7:651\u2013656.","journal-title":"Am J Neuroradiol"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0596"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0300369"},{"key":"e_1_3_2_25_2","first-page":"3249","article-title":"Adipogenesis in thyroid eye disease","volume":"41","author":"Crisp M","year":"2000","unstructured":"Crisp M, , Starkey KJ, , Lane C, , Ham J, , Ludgate M. 2000. Adipogenesis in thyroid eye disease. Invest Ophthalmol Vis Sci, 41:3249\u20133255.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-0436.1996.6040203.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.684351"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1156"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031427"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2012.733055"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2011.0160"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020987"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.1.8164"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(02)00323-5"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1089\/108076803321637627"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(01)00224-7"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2011.0097"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2013.0194","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2013.0194","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2013.0194","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:55:27Z","timestamp":1777701327000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2013.0194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["10.1089\/thy.2013.0194"],"URL":"https:\/\/doi.org\/10.1089\/thy.2013.0194","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12]]}}}