{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T19:49:58Z","timestamp":1757706598351},"reference-count":0,"publisher":"Proceedings of the National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1992,3,15]]},"abstract":"<jats:p>The binding of luteinizing hormone-releasing hormone (LH-RH) analogues to the human mammary tumor cell line MCF-7 and their effect on the cell proliferation was studied to elucidate their direct action on estrogen-dependent mammary tumors. The growth rate of these cells was doubled by the addition of 1 nM estradiol to cells maintained in an estrogen-deficient medium. Although the basal growth rate was only slightly inhibited by the LH-RH antagonist [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH (SB-75), the estrogen-stimulated growth was completely abolished by the antagonist. In contrast, the LH-RH agonist buserelin stimulated cell growth in estrogen-deficient medium, whereas it had no effect in the presence of estrogen. 125I-labeled buserelin was used for the measurement of LH-RH receptors on MCF-7 cells. A Scatchard plot analysis of buserelin-specific binding revealed a nonlinear plot, which suggested the presence of one high-affinity binding site with a Kd of 1.4 +\/- 1.0 nM and the remaining sites with low affinity (Kd = 1.3 +\/- 1.0 microM). The binding of 125I-labeled buserelin was displaced equally well by unlabeled buserelin and by the LH-RH antagonist SB-75, suggesting that both analogues are bound to the same receptor. When parallel experiments were performed with 125I-labeled SB-75, the binding was displaced by unlabeled SB-75 and other antagonists, but only partially displaced by unlabeled buserelin. The results suggest that in these mammary tumor cells there is a LH-RH antagonist binding site that is not recognizable by LH-RH agonists. This hypothesis was tested by measuring cell growth in the presence of both agonists and antagonists. It was found that SB-75 inhibited the stimulation of growth by buserelin, but buserelin did not prevent the inhibition by the antagonist of the estrogen-dependent growth. These results suggest that antagonists directly inhibit mammary tumor growth, not only by competing with LH-RH high-affinity receptors, but also by other mechanisms mediated by low-affinity antagonist binding sites.<\/jats:p>","DOI":"10.1073\/pnas.89.6.2336","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T12:18:24Z","timestamp":1149077904000},"page":"2336-2339","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Direct effects of luteinizing hormone-releasing hormone agonists and antagonists on MCF-7 mammary cancer cells."],"prefix":"10.1073","volume":"89","author":[{"given":"T","family":"Segal-Abramson","sequence":"first","affiliation":[{"name":"Clinical Biochemistry Department, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}]},{"given":"H","family":"Kitroser","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Department, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}]},{"given":"J","family":"Levy","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Department, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}]},{"given":"A V","family":"Schally","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Department, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}]},{"given":"Y","family":"Sharoni","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry Department, Faculty of Health Sciences, Soroka Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}]}],"member":"341","published-online":{"date-parts":[[1992,3,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.89.6.2336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:39:07Z","timestamp":1649871547000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.89.6.2336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,3,15]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1992,3,15]]}},"alternative-id":["10.1073\/pnas.89.6.2336"],"URL":"https:\/\/doi.org\/10.1073\/pnas.89.6.2336","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,3,15]]},"assertion":[{"value":"1992-03-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}