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Bones and adrenal organogenesis: how embryonic osteocalcin influences lifelong adrenal function
Typhanie Dumontet, Gary D. Hammer
Typhanie Dumontet, Gary D. Hammer
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Bones and adrenal organogenesis: how embryonic osteocalcin influences lifelong adrenal function

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Abstract

Osteocalcin is a hormone produced in bones by osteoblasts during bone formation. Numerous studies have demonstrated that adrenal gland–derived glucocorticoids inhibit osteocalcin production, which can ultimately cause deleterious bones loss. This loss establishes a unidirectional endocrine relationship between the adrenal glands and bone, however, whether osteocalcin reciprocally regulates glucocorticoid secretion remains unclear. In this issue of the JCI, Yadav and colleagues address how bone-derived osteocalcin influences adrenal organogenesis and function. Using a large variety of animal models, the authors established that embryonic osteocalcin signaling, specifically through the GPR158 receptor, regulates postnatal adrenal steroid concentrations throughout life. This work has translational potential, and we await future investigations that determine whether modulating osteocalcin levels could promote endogenous adrenocortical function in adrenocortical hypoplasia and glucocorticoid deficiency.

Authors

Typhanie Dumontet, Gary D. Hammer

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Figure 1

The bone-adrenal endocrine circuit.

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The bone-adrenal endocrine circuit.
Yadav and colleagues detailed how bo...
Yadav and colleagues detailed how bone-derived osteocalcin, produced by osteoblasts and released into the bloodstream, acts distantly on adrenal cortex cells. Through activation of GPR158, osteocalcin promotes adrenal cortex proliferation and differentiation during embryogenesis, in part via upregulation of the key steroidogenic genes Sf1 (also known as Nr5a1), Cyp11b1, Cyp11b2, Mc2r, Agtr1a, and Agtr1b (10). These results complement previously described glucocorticoid effects, thus completing the bone-adrenal endocrine circuit.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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