{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:23:19Z","timestamp":1781104999568,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1990,9]]},"abstract":"<jats:p>Inhibitory effects of the potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1,4-chloro-D-phenylalanine2,3- (3-pyridyl)-D- alanine3,D-citrulline6,D-alanine10]luteinizing hormone-releasing hormone (SB-75) free of edematogenic effects were investigated in male rats. In a study to determine the effect on luteinizing hormone levels in castrated male rats, SB-75 was injected s.c. in doses of 0.625, 1.25, 2.5, 5.0, and 10 micrograms. Blood samples were taken at different intervals for 48 hr. All doses of SB-75 significantly decreased luteinizing hormone levels for greater than 6 hr (P less than 0.01); this inhibition lasted for greater than 24 hr (P less than 0.01) with a dose of 5.0 micrograms and greater than 48 hr with 10 micrograms (P less than 0.05). Serum testosterone levels were also measured in intact male rats injected with SB-75 in doses of 25, 50, and 100 micrograms. All doses produced a dramatic fall in testosterone to castration levels 6 hr after injection (P less than 0.01); this inhibition of serum testosterone was maintained for greater than 72 hr, but only the 100-micrograms dose could keep testosterone in the castration range for greater than 24 hr (P less than 0.01). In another study using a specific RIA, we obtained the pharmacokinetic release pattern of SB-75 from two sustained delivery formulations of SB-75 pamoate microgranules and examined their effect on serum testosterone. After a single i.m. injection of 20 mg of one batch of microgranules, a large peak corresponding to SB-75 at 45.8 ng\/ml was observed, corresponding to the \"burst\" effect. Levels of the analog decreased to 19.6 ng\/ml on day 2, gradually reached a concentration of 4.7 ng\/ml on day 7, and kept declining thereafter. Testosterone levels were reduced on day 1 (P less than 0.01) and were maintained at low values for greater than 7 days (P less than 0.05). In rats injected with 10 mg of SB-75 pamoate microgranules of the second batch, SB-75 serum levels rose to 33 ng\/ml 3 hr after administration and then fell gradually to approximately 3.4 ng\/ml on day 16, but a second small peak was seen on day 28. Subsequently, the analog levels decreased slowly to 2.9 ng\/ml on day 42. At this time, testosterone serum levels were still significantly lower than in controls. These overall results demonstrate the efficacy of SB-75 in the suppression of the pituitary-gonadal axis. This modern luteinizing hormone-releasing hormone antagonist can possibly be used for treating sex hormone-sensitive cancers and other disorders.<\/jats:p>","DOI":"10.1073\/pnas.87.18.7100","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:26:26Z","timestamp":1149060386000},"page":"7100-7104","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":23,"title":["Prolonged inhibition of luteinizing hormone and testosterone levels in male rats with the luteinizing hormone-releasing hormone antagonist SB-75."],"prefix":"10.1073","volume":"87","author":[{"given":"L","family":"Bokser","sequence":"first","affiliation":[{"name":"Endocrine, Polypeptide and Cancer Institute, Tulane University School of Medicine, New Orleans, LA 70146."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Bajusz","sequence":"additional","affiliation":[{"name":"Endocrine, Polypeptide and Cancer Institute, Tulane University School of Medicine, New Orleans, LA 70146."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Groot","sequence":"additional","affiliation":[{"name":"Endocrine, Polypeptide and Cancer Institute, Tulane University School of Medicine, New Orleans, LA 70146."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A V","family":"Schally","sequence":"additional","affiliation":[{"name":"Endocrine, Polypeptide and Cancer Institute, Tulane University School of Medicine, New Orleans, LA 70146."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1990,9]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.87.18.7100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:22:30Z","timestamp":1649856150000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.87.18.7100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,9]]},"references-count":0,"journal-issue":{"issue":"18","published-print":{"date-parts":[[1990,9]]}},"alternative-id":["10.1073\/pnas.87.18.7100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.87.18.7100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,9]]},"assertion":[{"value":"1990-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}