title: Structure-activity relationships of a series of analogs of the endozepine octadecaneuropeptide (ODN(11)(-)(18)) on neurosteroid biosynthesis by hypothalamic explants.
abstract: We have previously shown that the endozepine octadecaneuropeptide (ODN) stimulates the biosynthesis of neurosteroids from frog hypothalamic explants. In the present study, we have investigated the structure-activity relationships of a series of analogs of the C-terminal octapeptide of ODN (OP) on neurosteroid formation. We found that OP and its cyclic analog cyclo1-8OP stimulate in a concentration-dependent manner the synthesis of various steroids including 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone and dehydroepiandrosterone. Deletion or Ala-substitution of the Arg1 or Pro2 residues of OP did not affect the activity of the peptide. In contrast, deletion or replacement of any of the amino acids of the C-terminal hexapeptide fragment totally abolished the effect of OP on neurosteroid biosynthesis. The present study indicates that the C-terminal hexapeptide of ODN/OP is the minimal sequence retaining full biological activity on steroid-producing neurons.
authors.affiliation: INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, 76821 Mont-Saint-Aignan, France.
authors.forename: Jean Luc Do
authors.initials: JL
authors.lastname: Rego
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.forename: Van
authors.initials: V
authors.lastname: Luu-The
authors.forename: Georges
authors.initials: G
authors.lastname: Pelletier
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Tonon
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
mesh_terms: D006907:17-alpha-Hydroxypregnenolone / Q000378:metabolism; D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003687:Dehydroepiandrosterone / Q000096:biosynthesis; D026261:Diazepam Binding Inhibitor / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004789:Enzyme Activation; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009479:Neuropeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis; D011893:Rana esculenta; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013329:Structure-Activity Relationship
chemical_list: D026261:Diazepam Binding Inhibitor; D009479:Neuropeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D013256:Steroids; C067529:diazepam binding inhibitor (33-50); D006907:17-alpha-Hydroxypregnenolone; D003687:Dehydroepiandrosterone; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase