title: Gonadotropin-releasing hormone stimulates the biosynthesis of pregnenolone sulfate and dehydroepiandrosterone sulfate in the hypothalamus.
abstract: The sulfated neurosteroids pregnenolone sulfate (Δ(5)PS) and dehydroepiandrosterone sulfate (DHEAS) are known to play a role in the control of reproductive behavior. In the frog Pelophylax ridibundus, the enzyme hydroxysteroid sulfotransferase (HST), responsible for the biosynthesis of Δ(5)PS and DHEAS, is expressed in the magnocellular nucleus and the anterior preoptic area, two hypothalamic regions that are richly innervated by GnRH1-containing fibers. This observation suggests that GnRH1 may regulate the formation of sulfated neurosteroids to control sexual activity. Double labeling of frog brain slices with HST and GnRH1 antibodies revealed that GnRH1-immunoreactive fibers are located in close vicinity of HST-positive neurons. The cDNAs encoding 3 GnRH receptors (designated riGnRHR-1, -2, and -3) were cloned from the frog brain. RT-PCR analyses revealed that riGnRHR-1 is strongly expressed in the hypothalamus and the pituitary whereas riGnRHR-2 and -3 are primarily expressed in the brain. In situ hybridization histochemistry indicated that GnRHR-1 and GnRHR-3 mRNAs are particularly abundant in preoptic area and magnocellular nucleus whereas the concentration of GnRHR-2 mRNA in these 2 nuclei is much lower. Pulse-chase experiments using tritiated Δ(5)P and DHEA as steroid precursors, and 3'-phosphoadenosine 5'-phosphosulfate as a sulfonate moiety donor, showed that GnRH1 stimulates, in a dose-dependent manner, the biosynthesis of Δ(5)PS and DHEAS in frog diencephalic explants. Because Δ(5)PS and DHEAS, like GnRH, stimulate sexual activity, our data strongly suggest that some of the behavioral effects of GnRH could be mediated via the modulation of sulfated neurosteroid production.
authors.affiliation: Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institut National de la Sante´ et de la Recherche Me´ dicale U982, Research Institute for Biomedecine (IRIB), International Associated Laboratory Samuel de Champlain, University of Rouen, 76821 Mont-Saint Aignan, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Burel
authors.forename: Jian Hua
authors.initials: JH
authors.lastname: Li
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Do-Rego
authors.forename: Ai Fen
authors.initials: AF
authors.lastname: Wang
authors.forename: Van
authors.initials: V
authors.lastname: Luu-The
authors.forename: Georges
authors.initials: G
authors.lastname: Pelletier
authors.forename: Yves
authors.initials: Y
authors.lastname: Tillet
authors.forename: Catherine
authors.initials: C
authors.lastname: Taragnat
authors.forename: Hyuk Bang
authors.initials: HB
authors.lastname: Kwon
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Seong
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism*; D004027:Diencephalon / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D011284:Pregnenolone / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011898:Ranidae; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015238:Sulfotransferases / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D011966:Receptors, LHRH; C018370:pregnenolone sulfate; D007987:Gonadotropin-Releasing Hormone; D019314:Dehydroepiandrosterone Sulfate; D011284:Pregnenolone; D015238:Sulfotransferases; C028152:alcohol sulfotransferase