Gonadotropin-releasing hormone stimulates the biosynthesis of pregnenolone sulfate and dehydroepiandrosterone sulfate in the hypothalamus
Résumé
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 (Mgd) and the anterior preoptic area (Poa), 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 three GnRH receptors (designated riGnRHR-1, -2, and -3) were cloned from the frog brain. Reverse transcription-polymerase chain reaction analyses revealed that riGnRHR-1 is strongly expressed in the hypothalamus and the pituitary while 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 Poa and Mgd whereas the concentration of GnRHR-2 mRNA in these two nuclei is much lower. Pulse-chase experiments using tritiated Δ(5)P and DHEA as steroid precursors, and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) 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. Since 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.
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Autre [q-bio.OT]
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