Abstract
The sulfated neurosteroids pregnenolone sulfate (Δ5PS) 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 Δ5PS 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 Δ5P 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 Δ5PS and DHEAS in frog diencephalic explants. Because Δ5PS 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2114-2128 |
| Number of pages | 15 |
| Journal | Endocrinology |
| Volume | 154 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2013 Jun 1 |
Fingerprint
ASJC Scopus subject areas
- Endocrinology
Cite this
Gonadotropin-releasing hormone stimulates the biosynthesis of pregnenolone sulfate and dehydroepiandrosterone sulfate in the hypothalamus. / Burel, Delphine; Li, Jian Hua; Do-Rego, Jean Luc; Wang, Ai Fen; Luu-The, Van; Pelletier, Georges; Tillet, Yves; Taragnat, Catherine; Kwon, Hyuk Bang; Seong, Jae Young; Vaudry, Hubert.
In: Endocrinology, Vol. 154, No. 6, 01.06.2013, p. 2114-2128.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gonadotropin-releasing hormone stimulates the biosynthesis of pregnenolone sulfate and dehydroepiandrosterone sulfate in the hypothalamus
AU - Burel, Delphine
AU - Li, Jian Hua
AU - Do-Rego, Jean Luc
AU - Wang, Ai Fen
AU - Luu-The, Van
AU - Pelletier, Georges
AU - Tillet, Yves
AU - Taragnat, Catherine
AU - Kwon, Hyuk Bang
AU - Seong, Jae Young
AU - Vaudry, Hubert
PY - 2013/6/1
Y1 - 2013/6/1
N2 - The sulfated neurosteroids pregnenolone sulfate (Δ5PS) 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 Δ5PS 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 Δ5P 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 Δ5PS and DHEAS in frog diencephalic explants. Because Δ5PS 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.
AB - The sulfated neurosteroids pregnenolone sulfate (Δ5PS) 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 Δ5PS 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 Δ5P 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 Δ5PS and DHEAS in frog diencephalic explants. Because Δ5PS 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.
UR - http://www.scopus.com/inward/record.url?scp=84878430388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878430388&partnerID=8YFLogxK
U2 - 10.1210/en.2013-1095
DO - 10.1210/en.2013-1095
M3 - Article
C2 - 23554453
AN - SCOPUS:84878430388
VL - 154
SP - 2114
EP - 2128
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 6
ER -