Inhibin A inhibits follicle-stimulating hormone (FSH) action by suppressing its receptor expression in cultured rat granulosa cells.
Inhibin has long been considered as a suppresser of follicle-stimulating hormone (FSH) secretion from anterior pituitary through pituitary-gonad negative feedback to regulate follicle development. We demonstrated that addition of inhibin A could significantly suppress FSH-induced FSHR mRNA level in cultured rat granulosa cells (GCs) measured by real-time PCR. The inhibin A exerted its action mainly by inhibiting FSHR promoter activity. Furthermore, exogenous inhibin A could dramatically decrease FSH-induced P450arom and P450scc level and suppress progesterone and estradiol production in the cultured GCs, but it did not decrease forskolin-induced steroidogenesis, indicating that the inhibitory effect of inhibin A on FSH action may be upstream of cAMP signaling. Inhibin A was also capable of suppressing FSH-induced expression of steroidogenic factor 1 (SF-1) and androgen receptor, but stimulating DAX-1 expression in the culture. Our study has provided new evidence to show that inhibin A is capable of feedback antagonizing FSH action on GCs by reducing FSHR expression at ovarian level via a short feedback loop. Transcriptional factor receptors, such as SF-1, AR and DAX-1 were involved in this regulation.
Lu
Cuiling
C
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China.
Yang
Wei
W
Chen
Min
M
Liu
Tao
T
Yang
Junling
J
Tan
Ping
P
Li
Lei
L
Hu
Xiaoqian
X
Fan
Cuihong
C
Hu
Zhaoyuan
Z
Liu
Yixun
Y
D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007265:Inhibins / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000502:physiology; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D054339:Steroidogenic Factor 1 / Q000502:physiology; D013256:Steroids / Q000096:biosynthesis
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539967:Nr0b1 protein, rat; D011944:Receptors, Androgen; D011962:Receptors, FSH; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D013256:Steroids; C422362:inhibin A; D005576:Colforsin; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D001141:Aromatase; D002786:Cholesterol Side-Chain Cleavage Enzyme