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

in Journal of Endocrinology
Authors:
H H Farman Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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K L Gustafsson Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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P Henning Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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L Grahnemo Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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V Lionikaite Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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S Movérare-Skrtic Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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J Wu Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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H Ryberg Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

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A Koskela Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland

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J Tuukkanen Unit of Cancer Research and Translational Medicine, MRC Oulu and Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland

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E R Levin Division of Endocrinology, Departments of Medicine and Biochemistry, University of California, Irvine, California, USA
The Long Beach VA Medical Center, Long Beach, California, USA

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C Ohlsson Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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M K Lagerquist Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Correspondence should be addressed to H H Farman: helen.farman@gu.se

*(C Ohlsson and M K Lagerquist contributed equally to this work)

DOI:
https://doi.org/10.1530/JOE-18-0406
Volume/Issue:
Volume 239: Issue 3
Article Type:
Research Article
Page Range:
303–312
Online Publication Date:
Dec 2018
Copyright:
© 2018 Society for Endocrinology 2018
Restricted access
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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.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2018 Society for Endocrinology 2018
Page(s):
10
Article Type:
Research Article
Received Date:
24 Aug 2018
Accepted Date:
04 Sep 2018
Print Publication Date:
01 Dec 2018
Online Publication Date:
Dec 2018
Keywords:
estrogen receptor α; male skeleton; bone mineral density; membrane-initiated steroid signaling

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