Dual mode of action of androgens on the skeleton: Are androgen receptor and estrogen receptor activation equally important at the same time and place?

2006 ◽  
Vol 3 (1) ◽  
pp. 15-17
Author(s):  
Katrien Venken ◽  
Dirk Vanderschueren
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Mode Of Action ◽  
Receptor Activation ◽  
Dual Mode

scholarly journals Testosterone and the Male Skeleton: A Dual Mode of Action

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Mieke Sinnesael ◽  
Steven Boonen ◽  
Frank Claessens ◽  
Evelien Gielen ◽  
Dirk Vanderschueren
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Bone Mass ◽  
Bone Turnover ◽  
Mode Of Action ◽  
Estrogen Receptor Alpha ◽  
Receptor Activation ◽  
Male Mice ◽  
Dual Mode ◽  
Receptor Alpha

Testosterone is an important hormone for both bone gain and maintenance in men. Hypogonadal men have accelerated bone turnover and increased fracture risk. In these men, administration of testosterone inhibits bone resorption and maintains bone mass. Testosterone, however, is converted into estradiol via aromatization in many tissues including male bone. The importance of estrogen receptor alpha activation as well of aromatization of androgens into estrogens was highlighted by a number of cases of men suffering from an inactivating mutation in the estrogen receptor alpha or in the aromatase enzyme. All these men typically had low bone mass, high bone turnover and open epiphyses. In line with these findings, cohort studies have confirmed that estradiol contributes to the maintenance of bone mass after reaching peak bone mass, with an association between estradiol and fractures in elderly men. Recent studies in knock-out mice have increased our understanding of the role of androgens and estrogens in different bone compartments. Estrogen receptor activation, but not androgen receptor activation, is involved in the regulation of male longitudinal appendicular skeletal growth in mice. Both the androgen and the estrogen receptor can independently mediate the cancellous bone-sparing effects of sex steroids in male mice. Selective KO studies of the androgen receptor in osteoblasts in male mice suggest that the osteoblast in the target cell for androgen receptor mediated maintenance of trabecular bone volume and coordination of bone matrix synthesis and mineralization. Taken together, both human and animal studies suggest that testosterone has a dual mode of action on different bone surfaces with involvement of both the androgen and estrogen receptor.

Lasofoxifene enhances vaginal mucus formation without causing hypertrophy and increases estrogen receptor ?? and androgen receptor in rats

2006 ◽  
Vol 13 (4) ◽  
pp. 609-620 ◽  
Author(s):  
Xiao-Ning Wang ◽  
Hollis A. Simmons ◽  
Christopher T. Salatto ◽  
Patricia G. Cosgrove ◽  
David D. Thompson
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor

Anthranilic diamides: A new class of insecticides with a novel mode of action, ryanodine receptor activation

2006 ◽  
Vol 84 (3) ◽  
pp. 196-214 ◽  
Author(s):  
D. Cordova ◽  
E.A. Benner ◽  
M.D. Sacher ◽  
J.J. Rauh ◽  
J.S. Sopa ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Mode Of Action ◽  
Receptor Activation ◽  
New Class

scholarly journals Sex Hormone Receptor Signaling in Bladder Cancer: A Potential Target for Enhancing the Efficacy of Conventional Non-Surgical Therapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1169
Author(s):  
Hiroki Ide ◽  
Hiroshi Miyamoto
Keyword(s):  
Bladder Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Surgical Therapy ◽  
Urothelial Cancer ◽  
Hormone Receptors ◽  
Estrogen Receptor Α ◽  
Vital Role ◽  
Sex Hormone ◽  
Sex Steroid Hormone

There have been critical problems in the non-surgical treatment for bladder cancer, especially residence to intravesical pharmacotherapy, including BCG immunotherapy, cisplatin-based chemotherapy, and radiotherapy. Recent preclinical and clinical evidence has suggested a vital role of sex steroid hormone-mediated signaling in the progression of urothelial cancer. Moreover, activation of the androgen receptor and estrogen receptor pathways has been implicated in modulating sensitivity to conventional non-surgical therapy for bladder cancer. This may indicate the possibility of anti-androgenic and anti-estrogenic drugs, apart from their direct anti-tumor activity, to function as sensitizers of such conventional treatment. This article summarizes available data suggesting the involvement of sex hormone receptors, such as androgen receptor, estrogen receptor-α, and estrogen receptor-β, in the progression of urothelial cancer, focusing on their modulation for the efficacy of conventional therapy, and discusses their potential of overcoming therapeutic resistance.

The androgen receptor is a tumor suppressor in estrogen receptor–positive breast cancer

2021 ◽  
Vol 27 (2) ◽  
pp. 310-320 ◽  
Author(s):  
Theresa E. Hickey ◽  
Luke A. Selth ◽  
Kee Ming Chia ◽  
Geraldine Laven-Law ◽  
Heloisa H. Milioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Tumor Suppressor ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

scholarly journals The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
D. A. Leach ◽  
A. Mohr ◽  
E. S. Giotis ◽  
E. Cil ◽  
A. M. Isac ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Human Lung ◽  
Cell Types ◽  
Receptor Activation ◽  
Surface Proteins ◽  
Mouse Lung ◽  
Lung Cells ◽  
Human Lung Cells ◽  
Cellular Entry ◽  
Experimental Data Analysis

AbstractSARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide—a well-tolerated drug widely used in advanced prostate cancer—reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.

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