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  • Title: Pituitary receptor site blockade by a gonadotropin-releasing hormone antagonist in vivo: mechanism of action.
    Author: Heber D, Dodson R, Swerdloff RS, Channabasavaiah K, Stewart JM.
    Journal: Science; 1982 Apr 23; 216(4544):420-1. PubMed ID: 6280278.
    Abstract:
    Administration of a potent gonadotropin-releasing hormone (GnRH) antagonist [Nac-L-Ala1,pCl-D-Phe2,D-Trp3,6]GnRH as a single subcutaneous injection to castrated adult male rats reduced, by more than 90 percent, both serum luteinizing hormone concentrations and specific pituitary GnRH receptor binding. This effect persisted for 24 hours. The dissociation rate of the antagonist from pituitary membrane homogenates was fourfold slower than the dissociation rate of a potent agonist. The prolonged in vivo inhibition of pituitary GnRH receptor binding and luteinizing hormone secretion by the GnRH antagonist may be mediated by the slower dissociation rate of the antagonist from its specific pituitary membrane receptor site.
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