title: Autoradiographic Study of Binding and Internalization of a Luteinizing Hormone-Releasing Hormone Antagonist [D-Nal, D-Cpa, A-D-Trp, D-Arg, D-Ala]LHRH by Rat Pituitary Gonadotrophs.
abstract: Abstract The binding and intracellular pathway of the radioiodinated luteinizing hormone-releasing hormone (LHRH) antagonist [D-Nal(1), D-Cpa(2), D-Trp(3), D-Arg(6), D-Ala(10)]LHRH in pituitary gonadotrophs was studied as a function of time after iv injection of label into intact and castrated female rats. In semithin (1 |im) sections, silver grains were exclusively localized over about 10% of anterior pituitary cells in intact animals. In castrated animals, only the large castration cells were labeled. In control rats injected with both iodinated antagonist and an excess of unlabeled peptide, no significant labeling could be detected. At the ultrastructural level, the silver grains were exclusively localized in gonadotrophic cells. The time-course study showed that 30 min and 60 min after injection a high proportion of the silver grains was associated with the plasma membrane. Six h after injection, an appreciable proportion of the label was found over intracellular organelles, especially lysosomes and secretory granules. These results indicate that the potent LHRH antagonist used in the present experiments binds selectively to gonadotrophs and is subsequently internalized but at a much lower rate than that observed with LHRH agonists. This slow internalization of the LHRH antagonist might be related to the normal endocytic processes which occur independently of receptor activation.
authors.affiliation: MRC Group in Molecular Endocrinology, Le Centre Hospitalier de I'Université Laval, Sainte-Foy, Québec G1V 4G2, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Badr
authors.forename: G
authors.initials: G
authors.lastname: Pelletier