Nitric Oxide-Mediated Regulation of GLUT by T3 and Follicle-Stimulating Hormone in Rat Granulosa Cells.
Thyroid hormones are important for normal reproductive function. Although 3,5,3'-triiodothyronine (T3) enhances follicle-stimulating hormone (FSH)-induced preantral follicle growth and granulosa cells development in vitro, little is known about the molecular mechanisms regulating ovarian development via glucose. In this study, we investigated whether and how T3 combines with FSH to regulate glucose transporter protein (GLUT) expression and glucose uptake in granulosa cells. In this study, we present evidence that T3 and FSH cotreatment significantly increased GLUT-1/GLUT-4 expression, and translocation in cells, as well as glucose uptake. These changes were accompanied by upregulation of nitric oxide (NO) synthase (NOS)3 expression, total NOS and NOS3 activity, and NO content in granulosa cells. Furthermore, we found that activation of the mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K)/Akt pathway is required for the regulation of GLUT expression, translocation, and glucose uptake by hormones. We also found that l-arginine upregulated GLUT-1/GLUT-4 expression and translocation, which were related to increased glucose uptake; however, these responses were significantly blocked by N(G)-nitro-l-arginine methylester. In addition, inhibiting NO production attenuated T3- and FSH-induced GLUT expression, translocation, and glucose uptake in granulosa cells. Our data demonstrate that T3 and FSH cotreatment potentiates cellular glucose uptake via GLUT upregulation and translocation, which are mediated through the activation of the mTOR/PI3K/Akt pathway. Meanwhile, NOS3/NO are also involved in this regulatory system. These findings suggest that GLUT is a mediator of T3- and FSH-induced follicular development.
College of Life Science, Capital Normal University, Beijing 100048, People's Republic of China.
Ye
Y
Tian
College of Life Science, Capital Normal University, Beijing 100048, People's Republic of China.
Yu
Y
Ding
College of Life Science, Capital Normal University, Beijing 100048, People's Republic of China.
Juan
J
Liu
College of Life Science, Capital Normal University, Beijing 100048, People's Republic of China.
Dai
D
Heng
College of Life Science, Capital Normal University, Beijing 100048, People's Republic of China.
Kaili
K
Xu
College of Life Science, Capital Normal University, Beijing 100048, People's Republic of China.
Wenbo
W
Liu
College of Life Science, Capital Normal University, Beijing 100048, People's Republic of China.
Cheng
C
Zhang
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics* / Q000378:metabolism; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000494:pharmacology*
D051246:Glucose Transport Proteins, Facilitative; D014284:Triiodothyronine; D009569:Nitric Oxide; D005640:Follicle Stimulating Hormone