title: A second endogenous molecular form of mammalian hypothalamic luteinizing hormone-releasing hormone (LHRH), (hydroxyproline9)LHRH, releases luteinizing hormone and follicle-stimulating hormone in vitro and in vivo.
abstract: In vitro and in vivo release of pituitary hormones were studied in the presence of (hydroxyproline9)LHRH ((Hyp)LHRH), a newly characterized endogenous molecular form of LHRH. Results were compared to those obtained with LHRH itself. (Hyp)LHRH, as LHRH, stimulated both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in a homothetic manner. The hydroxylated compound was, however, 24 times (in vitro) and 5 times (in vivo) less potent than LHRH. The lower activity of (Hyp)LHRH than of LHRH in the in vitro assay correlated well with a 28-fold lesser potency in a binding test using pituitary membrane preparations. The higher relative potency and the prolonged effect of (Hyp)LHRH in the in vivo test were related to a lesser susceptibility of the hydroxylated form to proteolytic degradation. Effects of LHRH and of (Hyp)LHRH were not additive, both peptides were equally able to desensitize gonadotrophs to a subsequent challenge by the other. Taken together, these observations suggest that both forms of LHRH act at the same receptor site. The lesser affinity of the hydroxylated compound is compensated to a certain extent by its higher resistance to enzymatic degradation. It is concluded that in spite of its lesser potency, (Hyp)LHRH may participate in the regulation of gonadotropins.
authors.affiliation: Unité de Dynamique des Systèmes Neuroendocriniens (U159) de l'INSERM, Centre Paul Broca, Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Gautron
authors.forename: P
authors.initials: P
authors.lastname: Leblanc
authors.forename: M T
authors.initials: MT
authors.lastname: Bluet-Pajot
authors.forename: E
authors.initials: E
authors.lastname: Pattou
authors.forename: A
authors.initials: A
authors.lastname: L'Héritier
authors.forename: F
authors.initials: F
authors.lastname: Mounier
authors.forename: G
authors.initials: G
authors.lastname: Ponce
authors.forename: V
authors.initials: V
authors.lastname: Audinot
authors.forename: R
authors.initials: R
authors.lastname: Rasolonjanahary
authors.forename: C
authors.initials: C
authors.lastname: Kordon
mesh_terms: D000818:Animals; D002369:Castration; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007987:Gonadotropin-Releasing Hormone; C074293:LHRH, hydroxyprolyl(9)-; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004229:Dithiothreitol