Regulated production of the pituitary hormone oxytocin from murine and human osteoblasts

Journal of Biological Chemistry

Benedetto

et al. 2012

Self Cite

Background:The mechanism underlying the anabolic effect of estrogen on the skeleton is unclear. Results: We report that estrogen-induced bone formation in mice occurs through oxytocin (OT) produced by osteoblasts in bone marrow. Conclusion: Feed-forward OT release in bone marrow by a rising estrogen level may facilitate rapid skeletal recovery after lactation. Significance: The study highlights a novel mechanism for estrogen action on bone.

“…We also show that estrogen induced robust OT and OTR expression in male osteoblasts (supplemental Fig. 1); the time course of the effect is concordant with that seen in female cells (17).…”

Section: Mouse Models-otrsupporting

confidence: 54%

“…In certain of these organs, estrogen regulates OT and/or OTR expression (15,16). Likewise, we found that OT is produced in abundance by bone marrow osteoblasts in response to estrogen, with the potential of exerting an anabolic effect on the skeleton (17). Estrogen at high doses is a skeletal anabolic (18), but its precise mechanism remains unknown.…”

mentioning

confidence: 72%

Bone Marrow Oxytocin Mediates the Anabolic Action of Estrogen on the Skeleton

Colaianni

Journal of Biological Chemistry

Benedetto

et al. 2012

Self Cite

“…Notably, the bone cell Fshr is a shorter isoform missing exon 9 (35). Likewise, and importantly, we also found that the ligands of certain of these receptors, such as oxytocin and Tsh-βv, are expressed in bone cells (34,36). We believe, therefore, that it is critical to begin to study local regulatory control mechanisms through which "pituitary" glycoprotein hormones interact with cytokines, such as Tnfα and others, in the local, as opposed to the central, control of bone remodeling and bone mass.…”

Section: Discussionmentioning

confidence: 74%

Genetic confirmation for a central role for TNFα in the direct action of thyroid stimulating hormone on the skeleton

Proc. Natl. Acad. Sci. U.S.A.

Zhu

Lü

et al. 2013

Self Cite

Clinical data showing correlations between low thyroid-stimulating hormone (TSH) levels and high bone turnover markers, low bone mineral density, and an increased risk of osteoporosis-related fractures are buttressed by mouse genetic and pharmacological studies identifying a direct action of TSH on the skeleton. Here we show that the skeletal actions of TSH deficiency are mediated, in part, through TNFα. Compound mouse mutants generated by genetically deleting the Tnf α gene on a Tshr −/− (homozygote) or Tshr +/− (heterozygote) background resulted in full rescue of the osteoporosis, low bone formation, and hyperresorption that accompany TSH deficiency. Studies using ex vivo bone marrow cell cultures showed that TSH inhibits and stimulates TNFα production from macrophages and osteoblasts, respectively. TNFα, in turn, stimulates osteoclastogenesis but also enhances the production in bone marrow of a variant TSHβ. This locally produced TSH suppresses osteoclast formation in a negative feedback loop. We speculate that TNFα elevations due to low TSH signaling in human hyperthyroidism contribute to the bone loss that has traditionally been attributed solely to high thyroid hormone levels.

“…In line with the ubiquitous distribution of OXTRs, cells of bone marrow also synthesize OXT, suggesting the existence of autocrine and paracrine interactions [106]. In vitro, OXT stimulates osteoblast differentiation and bone formation.…”

Section: Mechanism Of Actionmentioning

confidence: 84%

Pituitary-bone connection in skeletal regulation

Zaidi

Hormone Molecular Biology and Clinical Investigation

Liu

et al. 2016

Self Cite

Pituitary hormones have traditionally been thought to exert specific, but limited function on target tissues. More recently, the discovery of these hormones and their receptors in organs such as the skeleton suggests that pituitary hormones have more ubiquitous functions. Here, we discuss the interaction of growth hormone (GH), follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin and arginine vasopressin (AVP) with bone. The direct skeletal action of pituitary hormones therefore provides new insights and therapeutic opportunities for metabolic bone diseases, prominently osteoporosis.