scholarly journals The Bone Sparing Effects of 2-Methoxyestradiol Are Mediated via Estrogen Receptor-α in Male Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (11) ◽  
pp. 4200-4205 ◽  
Author(s):  
Anna L. Eriksson ◽  
Anna S. Wilhelmson ◽  
Johan B. Fagman ◽  
Henrik Ryberg ◽  
Antti Koskela ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Male Mice

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton

2018 ◽  
Vol 239 (3) ◽  
pp. 303-312 ◽  
Author(s):  
H H Farman ◽  
K L Gustafsson ◽  
P Henning ◽  
L Grahnemo ◽  
V Lionikaite ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Areal Bone Mineral Density ◽  
Male Mice ◽  
Mineral Density ◽  
Intact Male ◽  
Trabecular Thickness ◽  
Total Body

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

scholarly journals Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α

2020 ◽  
Author(s):  
Shivani N. Mann ◽  
Niran Hadad ◽  
Molly Nelson-Holte ◽  
Alicia R. Rothman ◽  
Roshini Sathiaseelan ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Chronic Diseases ◽  
Transcriptional Activation ◽  
Estrogen Receptor Α ◽  
Metabolic Parameters ◽  
Metabolic Effects ◽  
Male Rats ◽  
Male Mice ◽  
Dietary Interventions ◽  
Estradiol Treatment

ABSTRACTMetabolic dysfunction underlies several chronic diseases, many of which are exacerbated by obesity. Dietary interventions can reverse metabolic declines and slow aging, although compliance issues remain paramount. 17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 acts primarily through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals.

scholarly journals Testosterone Prevents Cutaneous Ischemia and Necrosis in Males Through Complementary Estrogenic and Androgenic Actions

2017 ◽  
Vol 37 (5) ◽  
pp. 909-919 ◽  
Author(s):  
Caroline Chenu ◽  
Marine Adlanmerini ◽  
Frederic Boudou ◽  
Elodie Chantalat ◽  
Anne-Laure Guihot ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Direct Action ◽  
Skin Flap ◽  
Treatment Strategies ◽  
Estrogen Receptor Α ◽  
Male Mice ◽  
Resistance Arteries ◽  
Estradiol Treatment ◽  
Impaired Wound Healing ◽  
17Β Estradiol

Objective— Chronic nonhealing wounds are a substantial medical concern and are associated with morbidity and mortality; thus, new treatment strategies are required. The first step toward personalized/precision medicine in this field is probably in taking sex differences into account. Impaired wound healing is augmented by ischemia, and we previously demonstrated that 17β-estradiol exerts a major preventive effect against ischemia-induced skin flap necrosis in female mice. However, the equivalent effects of testosterone in male mice have not yet been reported. We then investigated the role of steroid hormones in male mice using a skin flap ischemia model. Approach and Results— Castrated male mice developed skin necrosis after ischemia, whereas intact or castrated males treated with testosterone were equally protected. Testosterone can (1) activate the estrogen receptor after its aromatization into 17β-estradiol or (2) be reduced into dihydrotestosterone, a nonaromatizable androgen that activates the androgen receptor. We found that dihydrotestosterone protected castrated wild-type mice by promoting skin revascularization, probably through a direct action on resistance arteries, as evidenced using a complementary model of flow-mediated outward remodeling. 17β-estradiol treatment of castrated male mice also strongly protected them from ischemic necrosis through the activation of estrogen receptor-α by increasing skin revascularization and skin survival. Remarkably, 17β-estradiol improved skin survival with a greater efficiency than dihydrotestosterone. Conclusions— Testosterone provides males with a strong protection against cutaneous necrosis and acts through both its estrogenic and androgenic derivatives, which have complementary effects on skin survival and revascularization.

Obesity and Disturbed Lipoprotein Profile in Estrogen Receptor-α-Deficient Male Mice

2000 ◽  
Vol 278 (3) ◽  
pp. 640-645 ◽  
Author(s):  
Claes Ohlsson ◽  
Nina Hellberg ◽  
Paolo Parini ◽  
Olle Vidal ◽  
Mohammed Bohlooly ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Lipoprotein Profile ◽  
Male Mice

scholarly journals Susceptibility to Early Atherosclerosis in Male Mice Is Mediated by Estrogen Receptor α

2004 ◽  
Vol 24 (6) ◽  
pp. 1055-1061 ◽  
Author(s):  
Amparo Villablanca ◽  
Dennis Lubahn ◽  
Lauren Shelby ◽  
Kent Lloyd ◽  
Stephen Barthold
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Male Mice ◽  
Early Atherosclerosis

Roles of estrogen receptor α and β in the regulation of body weight and blood glucose level in male mice

2011 ◽  
Vol 71 ◽  
pp. e164
Author(s):  
Mariko Nakata ◽  
Kazuhiro Sano ◽  
Mumeko C. Tsuda ◽  
Nandini Vasudevan ◽  
Sonoko Ogawa
Keyword(s):  
Estrogen Receptor ◽  
Body Weight ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Estrogen Receptor Α ◽  
Male Mice

scholarly journals Global estrogen receptor-α knockout has differential effects on cortical and cancellous bone in aged male mice

FACETS ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 328-348
Author(s):  
Rebecca K. Dirkes ◽  
Nathan C. Winn ◽  
Thomas J. Jurrissen ◽  
Dennis B. Lubahn ◽  
Victoria J. Vieira-Potter ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cancellous Bone ◽  
Lumbar Vertebrae ◽  
Estrogen Receptor Α ◽  
Femoral Diaphysis ◽  
Male Mice ◽  
Micro Computed Tomography ◽  
Trabecular Microarchitecture ◽  
Skeletal Site ◽  
Trabecular Number

Estrogen receptor-α knockout (ERKO) in female rodents results in bone loss associated with increased osteocyte sclerostin expression; whether this also occurs in males is unknown. Here, we examined the effects of ERKO on femoral cortical geometry, trabecular microarchitecture, and osteocyte sclerostin expression of the femur and lumbar vertebrae. At 14 months of age, male ERKO and wild-type (WT) littermates ( n = 6 per group) were sacrificed, and femora and vertebra were collected. Cortical geometry and trabecular microarchitecture were assessed via micro-computed tomography; osteocyte sclerostin expression was assessed via immunohistochemistry. ANCOVA with body weight was used to compare ERKO and WT for cortical geometry; t-tests were used for all other outcomes. Regardless of skeletal site, ERKO mice had greater trabecular bone volume and trabecular number and decreased trabecular separation compared with WT. In the femoral diaphysis, ERKO had lower total area, cortical area, and cortical thickness compared with WT. The percentage of sclerostin+ osteocytes was increased in ERKO animals in cortical bone but not in cancellous bone of the femur or the lumbar vertebrae. In conclusion, ERKO improved trabecular microarchitecture in aged male mice, but negatively altered femoral cortical geometry associated with a trend towards increased cortical sclerostin expression.

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