Signal pathway of GnRH-III inhibiting FSH-induced steroidogenesis in granulosa cells.
Gonadotrophin-releasing hormone type 1 and type 2 have been demonstrated to inhibit follicle-stimulating hormone (FSH)-induced granulosa cell (GC) steroidogenesis. A third type of GnRH (GnRH-III) was also purified from salmon, its action on the FSH-regulated GC function, however is not clear. In the present study we demonstrated that the FSH-induced estrogen and progesterone production in cultured DES-treated GCs was significantly inhibited by GnRH-III. Furthermore, the FSH-stimulated steroidogenic acute regulatory protein and the enzymes for steroidigenesis, such as HSD3B2,aromatase and cytochrome P450 side-chain cleavage were also significantly suppressed by this peptide. The inhibitory action of GnRH-III on the FSH-induced steroidogenenisis was demonstrated via Akt and p38 mitogen-activated protein kinase signaling pathways through suppressing its own receptor expression. Further studies indicated that FSH could stimulate NR5A2 and upstream stimulatory factor (USF) activation, and their induction was significantly suppressed by the GnRH-III. Therefore, it is suggested that GnRH-III inhibiting FSH-induced steroidogenenisis in GCs might be by suppressing FSH-induced its own receptor expression via NR5A2 and USF transcriptional factors.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, No 5 Datun Road, Chaoyang District, Beijing 100101, China.
Cui-hong
CH
Fan
Cui-Ling
CL
Lu
Jun-Ling
JL
Yang
Xiao-Qian
XQ
Hu
Yu
Y
Ren
Huan
H
Cai
Min
M
Chen
Zhao-Yuan
ZY
Hu
Fei
F
Gao
Yi-Xun
YX
Liu
D000818:Animals; D002478:Cells, Cultured; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006107:Granulosa Cells / Q000378:metabolism*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004967:Estrogens; C448022:gonadotropin-releasing hormone-III; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D011761:Pyrrolidonecarboxylic Acid