Neuropeptide Y inhibits the biosynthesis of sulfated neurosteroids in the hypothalamus through activation of Y(1) receptors.
We have recently shown that hydroxysteroid sulfotransferase (HST), the enzyme responsible for the biosynthesis of pregnenolone sulfate (Delta(5)PS) and dehydroepiandrosterone sulfate (DHEAS), is expressed in neurons located in the anterior preoptic area and the dorsal magnocellular nucleus of the frog diencephalon. As these two nuclei are richly innervated by NPY-immunoreactive fibers, we investigated the possible implication of NPY in the control of Delta(5)PS and DHEAS biosynthesis. Double labeling of frog brain sections revealed that 42% of the HST-immunoreactive perikarya in the diencephalon were contacted by NPY-containing fibers. In situ hybridization studies showed that Y(1) and Y(5) receptor mRNAs are expressed in the anterior preoptic area and the dorsal magnocellular nucleus. Pulse-chase experiments with (35)S-labeled 3'-phosphoadenosine 5'-phosphosulfate as a sulfate donor demonstrated that frog NPY (fNPY) inhibited the conversion of [(3)H]Delta(5)P and [(3)H]dehydroepiandrosterone ([(3)H]DHEA) into [(3)H,(35)S]Delta(5)PS and [(3)H,(35)S]DHEAS by diencephalic explants. The inhibitory effect of fNPY on Delta(5)PS and DHEAS formation was mimicked by (pPYY) and [Leu(31),Pro(34)]pNPY, which is an agonist for non-Y(2) receptors in mammals, and was completely suppressed by the Y(1) receptor antagonist BIBP3226. Conversely, the Y(2) receptor agonist pNPY-(13-36) and the Y(5) receptor agonist [D-Trp(32)]pNPY did not significantly modify the biosynthesis of [(3)H,(35)S]Delta(5)PS and [(3)H,(35)S]DHEAS. The present study provides the first evidence for the innervation of neurosteroid-producing neurons by NPY fibers. Our data also demonstrate that NPY, acting via Y(1) receptors, exerts an inhibitory effect on the biosynthesis of sulfated neurosteroids.
Beaujean
Delphine
D
European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, INSERM U-413, UA Centre National de la Recherche Scientifique, University of Rouen, 76821 Mont-Saint-Aignan, France.
Do-Rego
Jean-Luc
JL
Galas
Ludovic
L
Mensah-Nyagan
Ayikoe G
AG
Fredriksson
Robert
R
Larhammar
Dan
D
Fournier
Alain
A
Luu-The
Van
V
Pelletier
Georges
G
Vaudry
Hubert
H
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004027:Diencephalon / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009841:Oligonucleotides / Q000096:biosynthesis / Q000235:genetics; D011895:Rana ridibunda; D017476:Receptors, Neuropeptide Y / Q000819:agonists*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
D007202:Indicators and Reagents; D009478:Neuropeptide Y; D009841:Oligonucleotides; D017476:Receptors, Neuropeptide Y; D013256:Steroids; D013431:Sulfates; C097212:neuropeptide Y-Y1 receptor; D019314:Dehydroepiandrosterone Sulfate; D015238:Sulfotransferases; C028152:alcohol sulfotransferase