RT Journal Article
SR Electronic
T1 Estrogen Signaling in Arcuate <em>Kiss1</em> Neurons Suppresses a Sex-Dependent Circuit That Promotes Dense Strong Bones in Female Mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 315283
DO 10.1101/315283
A1 Candice B. Herber
A1 William C. Krause
A1 Liping Wang
A1 James R. Bayrer
A1 Alfred Li
A1 Matthew Schmitz
A1 Aaron Fields
A1 Breanna Ford
A1 Michelle S. Reid
A1 Daniel K. Nomura
A1 Robert A. Nissenson
A1 Stephanie M. Correa
A1 Holly A. Ingraham
YR 2018
UL http://biorxiv.org/content/early/2018/05/16/315283.abstract
AB Central estrogen signaling coordinates energy expenditure, reproduction, and in concert with peripheral estrogen impacts skeletal homeostasis in female rodents. Here, we ablate estrogen receptor alpha (ERα) in the medial basal hypothalamus and find a robust bone phenotype only in female mice that results in exceptionally strong trabecular and cortical bones, whose density surpasses other reported mouse models. Stereotaxic guided deletion of ERα in the arcuate nucleus increases bone mass in both intact and estrogen-depleted females, confirming the central role of estrogen signaling in this sex-dependent bone phenotype. Loss of ERα activity in kisspeptin (Kiss1)-expressing cells is sufficient to recapitulate the bone phenotype, identifying Kiss1 neurons as a critical node in this powerful neuroskeletal circuit. We propose that this newly identified female brain-to-bone pathway exists as a homeostatic regulator to divert calcium and energy stores from bone building when energetic demands are high. Our work reveals a previously unknown target for the treatment of age-related bone disease.