Structure-activity relationships of a series of analogs of the endozepine octadecaneuropeptide (ODN(11)(-)(18)) on neurosteroid biosynthesis by hypothalamic explants.
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.
Rego
Jean Luc Do
JL
INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, 76821 Mont-Saint-Aignan, France.
Leprince
Jérôme
J
Luu-The
Van
V
Pelletier
Georges
G
Tonon
Marie-Christine
MC
Vaudry
Hubert
H
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
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