Plasma steroid profiling and response to trophins to illustrate intra-adrenal dynamics

F. McManus (Lead / Corresponding author), R. Fraser, E. Davies, J. M. C. Connell, E. M. Freel

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    The importance of corticosteroids in cardiovascular and other chronic disease is recognised. In addition, plasma steroid precursor: product ratios are useful and convenient indirect indicators of efficiency of key steroidogenic enzymes (aldosterone synthase, 11β-hydroxylase and 17α-hydroxylase). The use of liquid chromatography tandem mass spectrometry (LCMS/MS) has enabled measurement of numerous corticosteroid compounds simultaneously. However, normal responses to trophins and variation in salt intake are not well described. This study examined these parameters in a large group of healthy volunteers. 60 normotensive volunteers were recruited and underwent infusion of angiotensin II and ACTH, following low and high salt diet. Plasma steroid measurements at baseline and 30 minutes after infusion of trophin were obtained by LCMS. As expected, plasma mineralocorticoids rose in response to salt restriction and were suppressed with salt loading, ACTH infusion increased all corticosteroids, while AngII increased mineralocorticoids and suppressed glucocorticoid production. ACTH increased S: F but decreased DOC: B, thus the S: F ratio is a more appropriate index of 11β-hydroxylase efficiency. The B: F ratio increased following ACTH treatment and salt restriction. A larger proportion of plasma B than generally accepted may be derived from the zona glomerulosa and this ratio may be most informative of 17α-hydroxylase activity in salt replete subjects. Although DOC: aldosterone, B: aldosterone and 18-hydroxyB: aldosterone should provide indices of aldosterone synthase efficiency, responses of individual compounds to trophins suggest that none accurately reflect this. Based on these data, aldosterone synthase activity is most accurately reflected by aldosterone concentration alone.

    Original languageEnglish
    Pages (from-to)149-157
    Number of pages9
    JournalJournal of Endocrinology
    Volume224
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2015

    Fingerprint

    Cytochrome P-450 CYP11B2
    Mixed Function Oxygenases
    Aldosterone
    Salts
    Adrenocorticotropic Hormone
    Steroids
    Mineralocorticoids
    Adrenal Cortex Hormones
    Zona Glomerulosa
    Sodium-Restricted Diet
    Tandem Mass Spectrometry
    Liquid Chromatography
    Angiotensin II
    Glucocorticoids
    Volunteers
    Healthy Volunteers
    Chronic Disease
    Enzymes
    Therapeutics

    Cite this

    McManus, F., Fraser, R., Davies, E., Connell, J. M. C., & Freel, E. M. (2015). Plasma steroid profiling and response to trophins to illustrate intra-adrenal dynamics. Journal of Endocrinology, 224(2), 149-157. https://doi.org/10.1530/JOE-14-0561
    McManus, F. ; Fraser, R. ; Davies, E. ; Connell, J. M. C. ; Freel, E. M. / Plasma steroid profiling and response to trophins to illustrate intra-adrenal dynamics. In: Journal of Endocrinology. 2015 ; Vol. 224, No. 2. pp. 149-157.
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    McManus, F, Fraser, R, Davies, E, Connell, JMC & Freel, EM 2015, 'Plasma steroid profiling and response to trophins to illustrate intra-adrenal dynamics', Journal of Endocrinology, vol. 224, no. 2, pp. 149-157. https://doi.org/10.1530/JOE-14-0561

    Plasma steroid profiling and response to trophins to illustrate intra-adrenal dynamics. / McManus, F. (Lead / Corresponding author); Fraser, R.; Davies, E.; Connell, J. M. C.; Freel, E. M.

    In: Journal of Endocrinology, Vol. 224, No. 2, 01.02.2015, p. 149-157.

    Research output: Contribution to journalArticle

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    AB - The importance of corticosteroids in cardiovascular and other chronic disease is recognised. In addition, plasma steroid precursor: product ratios are useful and convenient indirect indicators of efficiency of key steroidogenic enzymes (aldosterone synthase, 11β-hydroxylase and 17α-hydroxylase). The use of liquid chromatography tandem mass spectrometry (LCMS/MS) has enabled measurement of numerous corticosteroid compounds simultaneously. However, normal responses to trophins and variation in salt intake are not well described. This study examined these parameters in a large group of healthy volunteers. 60 normotensive volunteers were recruited and underwent infusion of angiotensin II and ACTH, following low and high salt diet. Plasma steroid measurements at baseline and 30 minutes after infusion of trophin were obtained by LCMS. As expected, plasma mineralocorticoids rose in response to salt restriction and were suppressed with salt loading, ACTH infusion increased all corticosteroids, while AngII increased mineralocorticoids and suppressed glucocorticoid production. ACTH increased S: F but decreased DOC: B, thus the S: F ratio is a more appropriate index of 11β-hydroxylase efficiency. The B: F ratio increased following ACTH treatment and salt restriction. A larger proportion of plasma B than generally accepted may be derived from the zona glomerulosa and this ratio may be most informative of 17α-hydroxylase activity in salt replete subjects. Although DOC: aldosterone, B: aldosterone and 18-hydroxyB: aldosterone should provide indices of aldosterone synthase efficiency, responses of individual compounds to trophins suggest that none accurately reflect this. Based on these data, aldosterone synthase activity is most accurately reflected by aldosterone concentration alone.

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