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

Artikel i vetenskaplig tidskrift
Författare Helen H. Farman
Karin L. Gustafsson
Petra Henning
Louise Grahnemo
Vikte Lionikaite
Sofia Moverare-Skrtic
Jianyao Wu
Henrik Ryberg
A. Koskela
J. Tuukkanen
E. R. Levin
Claes Ohlsson
Marie Lagerquist
Publicerad i Journal of Endocrinology
Volym 239
Nummer/häfte 3
Sidor 303-312
ISSN 0022-0795
Publiceringsår 2018
Publicerad vid Centre for Bone and Arthritis Research
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 303-312
Språk en
Länkar dx.doi.org/10.1530/joe-18-0406
Ämnesord estrogen receptor alpha, male skeleton, bone mineral density, membrane-initiated steroid signaling, cortical bone, er-alpha, null mice, older men, estradiol, serum, mass, localization, extranuclear, specificity, Endocrinology & Metabolism, iences, v68, p1226, ates of america, v106, p2053, ates of america, v111, pe283
Ämneskategorier Klinisk medicin

Sammanfattning

The importance of estrogen receptor alpha (ER alpha) for the regulation of bone mass in males is well established. ERa mediates estrogenic effects both via nuclear and membraneinitiated ER alpha (mER alpha) signaling. The role of mERa signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERa signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ER alpha 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 (mu CT) 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, mER alpha 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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