BMP-9 downregulates StAR expression and progesterone production by activating both SMAD1/5/8 and SMAD2/3 signaling pathways in human granulosa-lutein cells obtained from gonadotropins induced ovarian cycles

2021 ◽  
pp. 110089
Author(s):  
Lanlan Fang ◽  
Qiongqiong Jia ◽  
Boqun Liu ◽  
Yang Yan ◽  
Xiaoyu Han ◽  
...  
Endocrinology ◽  
2017 ◽  
Vol 158 (10) ◽  
pp. 3281-3291 ◽  
Author(s):  
Xuan Dang ◽  
Qinling Zhu ◽  
Yaqiong He ◽  
Yuan Wang ◽  
Yao Lu ◽  
...  

Endocrinology ◽  
2015 ◽  
Vol 156 (12) ◽  
pp. 4684-4694 ◽  
Author(s):  
Lanlan Fang ◽  
Hsun-Ming Chang ◽  
Jung-Chien Cheng ◽  
Yiping Yu ◽  
Peter C. K. Leung ◽  
...  

Growth differentiation factor-8 (GDF-8) has been recently shown to be expressed in human granulosa cells, and the mature form of GDF-8 protein can be detected in the follicular fluid. However, the biological function and significance of this growth factor in the human ovary remains to be determined. Here, we investigated the effects of GDF-8 on steroidogenic enzyme expression and the potential mechanisms of action in luteinized human granulosa cells. We demonstrated that treatment with GDF-8 did not affect the mRNA levels of P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase, whereas it significantly down-regulated steroidogenic acute regulatory protein (StAR) expression and decreased progesterone production. The suppressive effect of GDF-8 on StAR expression was abolished by the inhibition of the TGF-β type I receptor. In addition, treatment with GDF-8 activated both Smad2/3 and ERK1/2 signaling pathways. Furthermore, knockdown of activin receptor-like kinase 5 reversed the effects of GDF-8 on Smad2/3 phosphorylation and StAR expression. The inhibition of Smad3 or ERK1/2 signaling pathways attenuated the GDF-8-induced down-regulation of StAR and production of progesterone. Interestingly, the concentrations of GDF-8 were negatively correlated with those of progesterone in human follicular fluid. These results indicate a novel autocrine function of GDF-8 to down-regulate StAR expression and decrease progesterone production in luteinized human granulosa cells, most likely through activin receptor-like kinase 5-mediated Smad3 and ERK1/2 signaling pathways. Our findings suggest that granulosa cells might play a critical role in the regulation of progesterone production to prevent premature luteinization during the final stage of folliculogenesis.


2018 ◽  
Vol 461 ◽  
pp. 89-99 ◽  
Author(s):  
Long Bai ◽  
Hsun-Ming Chang ◽  
Jung-Chien Cheng ◽  
Guiyan Chu ◽  
Peter C.K. Leung ◽  
...  

2020 ◽  
Vol 134 (5) ◽  
pp. 473-512 ◽  
Author(s):  
Ryan P. Ceddia ◽  
Sheila Collins

Abstract With the ever-increasing burden of obesity and Type 2 diabetes, it is generally acknowledged that there remains a need for developing new therapeutics. One potential mechanism to combat obesity is to raise energy expenditure via increasing the amount of uncoupled respiration from the mitochondria-rich brown and beige adipocytes. With the recent appreciation of thermogenic adipocytes in humans, much effort is being made to elucidate the signaling pathways that regulate the browning of adipose tissue. In this review, we focus on the ligand–receptor signaling pathways that influence the cyclic nucleotides, cAMP and cGMP, in adipocytes. We chose to focus on G-protein–coupled receptor (GPCR), guanylyl cyclase and phosphodiesterase regulation of adipocytes because they are the targets of a large proportion of all currently available therapeutics. Furthermore, there is a large overlap in their signaling pathways, as signaling events that raise cAMP or cGMP generally increase adipocyte lipolysis and cause changes that are commonly referred to as browning: increasing mitochondrial biogenesis, uncoupling protein 1 (UCP1) expression and respiration.


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