scholarly journals Defects of Prostate Development and Reproductive System in the Estrogen Receptor-α Null Male Mice

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 251-259 ◽  
Author(s):  
Ming Chen ◽  
Iawen Hsu ◽  
Andrew Wolfe ◽  
Sally Radovick ◽  
KuoHsiang Huang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Reproductive System ◽  
Serum Testosterone ◽  
Branching Morphogenesis ◽  
Estrogen Receptor Α ◽  
Seminiferous Tubules ◽  
Male Mice ◽  
Stromal Compartment ◽  
Proliferation And Differentiation ◽  
The Impact

The estrogen receptor-α knockout (ERαKO, ERα−/−) mice were generated via the Cre-loxP system by mating floxed ERα mice with β-actin (ACTB)-Cre mice. The impact of ERα gene deletion in the male reproductive system was investigated. The ACTB-Cre/ERα−/− male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ERα−/− male mice are 2-fold elevated. The ACTB-Cre/ERα−/− testes consist of atrophic and degenerating seminiferous tubules with less cellularity in the disorganized seminiferous epithelia. Furthermore, the ventral and dorsal-lateral prostates of ACTB-Cre/ERα−/− mice display reduced branching morphogenesis. Loss of ERα could also be responsible for the decreased fibroblast proliferation and changes in the stromal content. In addition, we found bone morphogenetic protein, a mesenchymal inhibitor of prostatic branching morphogenesis, is significantly up-regulated in the ACTB-Cre/ERα−/− prostates. Collectively, these results suggest that ERα is required for male fertility, acts through a paracrine mechanism to regulate prostatic branching morphogenesis, and is involved in the proliferation and differentiation of prostatic stromal compartment. Newly generated ACTB-Cre/Estrogen receptor alpha knockout (ERα-/-) male mice show that ERα acts through a paracrine mechanism to regulate prostatic branching morphogenesis and is involved in the proliferation and differentiation of prostatic stoma.

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 Bisphenol A alters differentiation of Leydig cells in the rabbit fetal testis

2020 ◽  
Vol 52 ◽  
Author(s):  
Alexis Paulina Ortega-García ◽  
Verónica Díaz-Hernández ◽  
Pedro Collazo-Saldaña ◽  
Horacio Merchant-Larios
Keyword(s):  
Bisphenol A ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Disruptive Effect ◽  
Paracrine Signaling ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Tissue Compartments ◽  
Fetal Organs ◽  
The Impact

The endocrine disruptor Bisphenol A (BPA) crosses the placental barrier and reaches the fetal organs, including the gonads. In the testis, fetal Leydig cells (FLC) produce testosterone required for the male phenotype and homeostatic cell-cell signaling in the developing testis. Although it is known that BPA affects cell proliferation and differentiation in FLC, results concerning the mechanism involved are contradictory, mainly due to differences among species. Fast developing fetal gonads of rodents lack cortex and medulla, whereas species with more extended gestation periods form these two tissue compartments. The rabbit provides a good subject for studying the disruptive effect of BPA in fetal Leydig and possible postnatal endocrine consequences in adult Leydig cells. Here, we investigated the impact of BPA administered to pregnant rabbits does, on the FLC population of the developing testes. Using qRT-PCR, we assessed the levels of SF1, CYP11A1, 3β-HSD, and androgen receptor (AR) genes, and levels of fetal serum testosterone were measured by ELISA. These levels correlated with both the mitotic activity and the ultrastructural differentiation of the FLC by confocal and electron microscopy, respectively. Results indicate that BPA alters the expression levels of essential genes involved in androgen paracrine signaling, modifies the proliferation and differentiation of the FLCs, and alters the levels of serum testosterone after birth. Thus, BPA may change the postnatal levels of serum testosterone due to the impaired FLC population formed by the proliferating stem and non-proliferating cytodifferentiated FLC.

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
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