TGF-β1 downregulates StAR expression and decreases progesterone production through Smad3 and ERK1/2 signaling pathways in human granulosa cells
The Journal of Clinical Endocrinology & Metabolism, 2014•academic.oup.com
Context: Regulation of progesterone production in granulosa cells is important for normal
reproductive functions. Steroidogenic acute regulatory protein (StAR) is recognized as the
key regulatory protein involved in the rate-limiting step of steroidogenesis. TGF-β1 protein is
detected in human follicular fluid, and TGF-β1 and its receptors are expressed in human
granulosa cells. However, the functional role of TGF-β1 in the regulation of StAR expression
and progesterone production in human granulosa cells remains unknown. Objective: Our …
reproductive functions. Steroidogenic acute regulatory protein (StAR) is recognized as the
key regulatory protein involved in the rate-limiting step of steroidogenesis. TGF-β1 protein is
detected in human follicular fluid, and TGF-β1 and its receptors are expressed in human
granulosa cells. However, the functional role of TGF-β1 in the regulation of StAR expression
and progesterone production in human granulosa cells remains unknown. Objective: Our …
Context
Regulation of progesterone production in granulosa cells is important for normal reproductive functions. Steroidogenic acute regulatory protein (StAR) is recognized as the key regulatory protein involved in the rate-limiting step of steroidogenesis. TGF-β1 protein is detected in human follicular fluid, and TGF-β1 and its receptors are expressed in human granulosa cells. However, the functional role of TGF-β1 in the regulation of StAR expression and progesterone production in human granulosa cells remains unknown.
Objective
Our objective was to investigate the effects of TGF-β1 on StAR expression and progesterone production in human granulosa cells.
Design and Setting
SVOG cells are human granulosa cells that were obtained from women undergoing in vitro fertilization and immortalized with SV40 large T antigen. SVOG cells were used to investigate the effects of TGF-β1 on StAR expression and progesterone production at an academic research center.
Main Outcome Measures
Levels of mRNA and protein were examined by RT-qPCR and western blotting, respectively. The accumulation levels of progesterone were measured by enzyme-linked immunosorbent assay (ELISA).
Results
TGF-β1 treatment downregulated StAR expression and decreased progesterone production. The suppressive effects of TGF-β1 on StAR expression and progesterone production were abolished by the inhibition of TGF-β type I receptor. In addition, treatment with TGF-β1 activated the Smad2/3 and ERK1/2 signaling pathways. The inhibition of the Smad3 and ERK1/2 signaling pathways attenuated the TGF-β1–induced downregulation of StAR expression and progesterone production.
Conclusion
TGF-β1 downregulated StAR expression and decreased progesterone production by activating the Smad3 and ERK1/2 signaling pathways in human granulosa cells.
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