Anabolic action of parathyroid hormone regulated by the β2-adrenergic receptor.

Abstract:

:Parathyroid hormone (PTH), the major calcium-regulating hormone, and norepinephrine (NE), the principal neurotransmitter of sympathetic nerves, regulate bone remodeling by activating distinct cell-surface G protein-coupled receptors in osteoblasts: the parathyroid hormone type 1 receptor (PTHR) and the β(2)-adrenergic receptor (β(2)AR), respectively. These receptors activate a common cAMP/PKA signal transduction pathway mediated through the stimulatory heterotrimeric G protein. Activation of β(2)AR via the sympathetic nervous system decreases bone formation and increases bone resorption. Conversely, daily injection of PTH (1-34), a regimen known as intermittent (i)PTH treatment, increases bone mass through the stimulation of trabecular and cortical bone formation and decreases fracture incidences in severe cases of osteoporosis. Here, we show that iPTH has no osteoanabolic activity in mice lacking the β(2)AR. β(2)AR deficiency suppressed both iPTH-induced increase in bone formation and resorption. We showed that the lack of β(2)AR blocks expression of iPTH-target genes involved in bone formation and resorption that are regulated by the cAMP/PKA pathway. These data implicate an unexpected functional interaction between PTHR and β(2)AR, two G protein-coupled receptors from distinct families, which control bone formation and PTH anabolism.

authors

Hanyu R,Wehbi VL,Hayata T,Moriya S,Feinstein TN,Ezura Y,Nagao M,Saita Y,Hemmi H,Notomi T,Nakamoto T,Schipani E,Takeda S,Kaneko K,Kurosawa H,Karsenty G,Kronenberg HM,Vilardaga JP,Noda M

doi

10.1073/pnas.1109036109

subject

Has Abstract

pub_date

2012-05-08 00:00:00

pages

7433-8

issue

19

eissn

0027-8424

issn

1091-6490

pii

1109036109

journal_volume

109

pub_type

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