Editing Adrenocorticotropic hormone (section)

==ACTH receptors outside the adrenal gland==
As indicated above, ACTH is a cleavage product of the pro-hormone, [[proopiomelanocortin]] (POMC), which also produces other hormones including [[α-MSH]] that stimulates the production of [[melanin]]. A family of related receptors mediates the actions of these hormones, the MCR, or [[melanocortin receptor]] family. These are mainly not associated with the [[pituitary]]-[[adrenal]] axis. MC2R is the [[ACTH receptor]].<ref name="pmid15383650">{{cite journal | vauthors=Slominski A, Tobin DJ, Shibahara S, Wortsman J | title=Melanin pigmentation in mammalian skin and its hormonal regulation | journal= [[Physiological Reviews]] | volume=84 | issue=4 | pages=1155–1228 | year=2004 | doi= 10.1152/physrev.00044.2003 | pmid = 15383650}}</ref>  

While it has a crucial function in regulating the adrenal glands, it is also expressed elsewhere in the body, specifically in the [[osteoblast]], which is responsible for making new bone, a continual and highly regulated process in the bodies of air-breathing vertebrates.<ref name="pmid20392225">{{cite journal | vauthors = Isales CM, Zaidi M, Blair HC | title = ACTH is a novel regulator of bone mass | journal = Annals of the New York Academy of Sciences | volume = 1192 | issue = 1 | pages = 110–6 | date = March 2010 | pmid = 20392225 | doi = 10.1111/j.1749-6632.2009.05231.x | s2cid = 24378203 | bibcode = 2010NYASA1192..110I }}</ref> The functional expression of MC2R on the osteoblast was discovered by Isales et alia in 2005.<ref name="pmid15804492">{{cite journal | vauthors = Zhong Q, Sridhar S, Ruan L, Ding KH, Xie D, Insogna K, Kang B, Xu J, Bollag RJ, Isales CM | display-authors = 6 | title = Multiple melanocortin receptors are expressed in bone cells | journal = Bone | volume = 36 | issue = 5 | pages = 820–31 | date = May 2005 | pmid = 15804492 | doi = 10.1016/j.bone.2005.01.020 }}</ref> Since that time, it has been demonstrated that the response of bone forming cells to ACTH includes production of [[VEGF]], as it does in the adrenal. This response might be important in maintaining osteoblast survival under some conditions.<ref name="pmid20421485">{{cite journal | vauthors = Zaidi M, Sun L, Robinson LJ, Tourkova IL, Liu L, Wang Y, Zhu LL, Liu X, Li J, Peng Y, Yang G, Shi X, Levine A, Iqbal J, Yaroslavskiy BB, Isales C, Blair HC | display-authors = 6 | title = ACTH protects against glucocorticoid-induced osteonecrosis of bone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 19 | pages = 8782–7 | date = May 2010 | pmid = 20421485 | pmc = 2889316 | doi = 10.1073/pnas.0912176107 | bibcode = 2010PNAS..107.8782Z | doi-access = free }}</ref> If this is physiologically important, it probably functions in conditions with short-period or intermittent ACTH signaling, since with continual exposure of osteoblasts to ACTH, the effect was lost in a few hours.