scholarly journals Estrogen receptor‐α mediates an intraovarian negative feedback loop on thecal cell steroidogenesis via modulation of Cyp17a1 (cytochrome P450, steroid 17α‐hydroxylase/17,20 μlyase) expression

2006 ◽  
Vol 21 (2) ◽  
pp. 586-595 ◽  
Author(s):  
Fuminori Taniguchi ◽  
John F. Couse ◽  
Karina F. Rodriguez ◽  
Judith M. A. Emmen ◽  
Donald Poirier ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cytochrome P450 ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Estrogen Receptor Α ◽  
Negative Feedback Loop ◽  
Thecal Cell

scholarly journals Estrogen-regulated feedback loop limits the efficacy of estrogen receptor–targeted breast cancer therapy

2018 ◽  
Vol 115 (31) ◽  
pp. 7869-7878 ◽  
Author(s):  
Tengfei Xiao ◽  
Wei Li ◽  
Xiaoqing Wang ◽  
Han Xu ◽  
Jixin Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Therapy Resistance ◽  
Negative Feedback Loop ◽  
Endocrine Therapy Resistance ◽  
Estrogen Receptor Positive ◽  
Underlying Mechanisms

Endocrine therapy resistance invariably develops in advanced estrogen receptor-positive (ER+) breast cancer, but the underlying mechanisms are largely unknown. We have identified C-terminal SRC kinase (CSK) as a critical node in a previously unappreciated negative feedback loop that limits the efficacy of current ER-targeted therapies. Estrogen directly drives CSK expression in ER+ breast cancer. At low CSK levels, as is the case in patients with ER+ breast cancer resistant to endocrine therapy and with the poorest outcomes, the p21 protein-activated kinase 2 (PAK2) becomes activated and drives estrogen-independent growth. PAK2 overexpression is also associated with endocrine therapy resistance and worse clinical outcome, and the combination of a PAK2 inhibitor with an ER antagonist synergistically suppressed breast tumor growth. Clinical approaches to endocrine therapy-resistant breast cancer must overcome the loss of this estrogen-induced negative feedback loop that normally constrains the growth of ER+ tumors.

scholarly journals Smad2/3 Activation Regulates Smad1/5/8 Signaling via a Negative Feedback Loop to Inhibit 3T3-L1 Adipogenesis

2021 ◽  
Vol 22 (16) ◽  
pp. 8472
Author(s):  
Senem Aykul ◽  
Jordan Maust ◽  
Vijayalakshmi Thamilselvan ◽  
Monique Floer ◽  
Erik Martinez-Hackert
Keyword(s):  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Adipose Tissues ◽  
Family Growth ◽  
Simultaneous Activation ◽  
Adipocyte Hypertrophy ◽  
Adipocyte Development ◽  
Energy Surplus

Adipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia. The latter, also known as adipogenesis, is a process by which multipotent precursors differentiate to form mature adipocytes. This process is directed by developmental cues that include members of the TGF-β family. Our goal here was to elucidate, using the 3T3-L1 adipogenesis model, how TGF-β family growth factors and inhibitors regulate adipocyte development. We show that ligands of the Activin and TGF-β families, several ligand traps, and the SMAD1/5/8 signaling inhibitor LDN-193189 profoundly suppressed 3T3-L1 adipogenesis. Strikingly, anti-adipogenic traps and ligands engaged the same mechanism of action involving the simultaneous activation of SMAD2/3 and inhibition of SMAD1/5/8 signaling. This effect was rescued by the SMAD2/3 signaling inhibitor SB-431542. By contrast, although LDN-193189 also suppressed SMAD1/5/8 signaling and adipogenesis, its effect could not be rescued by SB-431542. Collectively, these findings reveal the fundamental role of SMAD1/5/8 for 3T3-L1 adipogenesis, and potentially identify a negative feedback loop that links SMAD2/3 activation with SMAD1/5/8 inhibition in adipogenic precursors.

scholarly journals HIC1 and miR-23~27~24 clusters form a double-negative feedback loop in breast cancer

2016 ◽  
Vol 24 (3) ◽  
pp. 421-432 ◽  
Author(s):  
Yanbo Wang ◽  
Hongwei Liang ◽  
Geyu Zhou ◽  
Xiuting Hu ◽  
Zhengya Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Double Negative
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