title: Steroid profiling reveals widespread local regulation of glucocorticoid levels during mouse development.
abstract: Glucocorticoids (GCs) are produced by the adrenal glands and circulate in the blood to coordinate organismal physiology. In addition, different tissues may independently regulate their local GC levels via local GC synthesis. Here, we find that in the mouse, endogenous GCs show tissue-specific developmental patterns, rather than mirroring GCs in the blood. Using solid-phase extraction, HPLC, and specific immunoassays, we quantified endogenous steroids and found that in tissues of female and male mice, (1) local GC levels can be much higher than systemic GC levels, (2) local GCs follow age-related patterns different from those of systemic GCs, and (3) local GCs have identities different from those of systemic GCs. For example, whereas corticosterone is the predominant circulating adrenal GC in mice, high concentrations of cortisol were measured in neonatal thymus, bone marrow, and heart. The presence of cortisol was confirmed with liquid chromatography-tandem mass spectrometry. In addition, gene expression of steroidogenic enzymes was detected across multiple tissues, consistent with local GC production. Our results demonstrate that local GCs can differ from GCs in circulating blood. This finding suggests that steroids are widely used as local (paracrine or autocrine) signals, in addition to their classic role as systemic (endocrine) signals. Local GC regulation may even be the norm, rather than the exception, especially during development.
authors.affiliation: Departments of Psychology (M.D.T., C.M., K.K.S.), Zoology (M.D.T., D.A.C., N.A., K.K.S.), Microbiology and Immunology (A.W.P., N.A.), and Fisheries (D.A.C.) and Brain Research Centre (K.K.S.), University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada; Department of Biological Sciences (B.A.S.), Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada; and Department of Pathology and Laboratory Medicine (J.G.V.D.G., D.T.H.), St. Paul's Hospital, Vancouver, British Columbia V6Z 1Y6, Canada.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Taves
authors.forename: Adam W
authors.initials: AW
authors.lastname: Plumb
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Sandkam
authors.forename: Chunqi
authors.initials: C
authors.lastname: Ma
authors.forename: Jessica Grace
authors.initials: JG
authors.lastname: Van Der Gugten
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Holmes
authors.forename: David A
authors.initials: DA
authors.lastname: Close
authors.forename: Ninan
authors.initials: N
authors.lastname: Abraham
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Soma
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D048788:Growth and Development; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis* / Q000097:blood; D013950:Thymus Gland / Q000378:metabolism
chemical_list: D013256:Steroids