Extra-nuclear Effects of Estrogen on Cortical Bone in Males Require ERαAF-1

Overview

Journal J Mol Endocrinol

Specialties Endocrinology
Molecular Biology

Date 2017 Jan 7

PMID 28057769

Citations 2

Authors

H H Farman

J Wu

K L Gustafsson

S H Windahl

S H Kim

J A Katzenellenbogen

C Ohlsson

M K Lagerquist

Affiliations

Soon will be listed here.

Abstract

Estradiol (E2) signaling via estrogen receptor alpha (ERα) is important for the male skeleton as demonstrated by ERα inactivation in both mice and man. ERα mediates estrogenic effects not only by translocating to the nucleus and affecting gene transcription but also by extra-nuclear actions e.g., triggering cytoplasmic signaling cascades. ERα contains various domains, and the role of activation function 1 (ERαAF-1) is known to be tissue specific. The aim of this study was to determine the importance of extra-nuclear estrogen effects for the skeleton in males and to determine the role of ERαAF-1 for mediating these effects. Five-month-old male wild-type (WT) and ERαAF-1-inactivated (ERαAF-1) mice were orchidectomized and treated with equimolar doses of 17β-estradiol (E2) or an estrogen dendrimer conjugate (EDC), which is incapable of entering the nucleus and thereby only initiates extra-nuclear ER actions or their corresponding vehicles for 3.5 weeks. As expected, E2 treatment increased cortical thickness and trabecular bone volume per total volume (BV/TV) in WT males. EDC treatment increased cortical thickness in WT males, whereas no effect was detected in trabecular bone. In ERαAF-1 males, E2 treatment increased cortical thickness, but did not affect trabecular bone. Interestingly, the effect of EDC on cortical bone was abolished in ERαAF-1 mice. In conclusion, extra-nuclear estrogen signaling affects cortical bone mass in males, and this effect is dependent on a functional ERαAF-1. Increased knowledge regarding estrogen signaling mechanisms in the regulation of the male skeleton may aid the development of new treatment options for male osteoporosis.

Citing Articles

Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications.

Emmanuelle N, Marie-Cecile V, Florence T, Jean-Francois A, Francoise L, Coralie F Int J Mol Sci. 2021; 22(4).

PMID: 33557249 PMC: 7913980. DOI: 10.3390/ijms22041568.

Respective role of membrane and nuclear estrogen receptor (ER) α in the mandible of growing mice: Implications for ERα modulation.

Vinel A, Coudert A, Buscato M, Valera M, Ostertag A, Katzenellenbogen J J Bone Miner Res. 2018; 33(8):1520-1531.

PMID: 29624728 PMC: 6563159. DOI: 10.1002/jbmr.3434.

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