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The Pathophysiology of Circulating Corticotropin-Releasing Hormone-Binding Protein Levels in the Human

Department of Endocrinology, St. Bartholomew’s Hospital (P.J.T., M.K., A.B.G.), West Smithfield, London, United Kingdom EC1A 7BE; the Department of Biochemistry and Physiology, University of Reading (R.J.W., P.J.L.), Reading, United Kingdom RG6 6AJ; the Institute of Endocrinology (V.P.), 11000 Belgrade, Yugoslavia; and the Department of Medicine, University of Birmingham, Queen Elizabeth Hospital (P.M.S.), Edgbaston, Birmingham, United Kingdom B15 2TH

Address all correspondence and requests for reprints: Dr. P. J. Trainer, Department of Endocrinology, St. Bartholomew’s Hospital, West Smithfield, London, United Kingdom EC1A 7BE. E-mail: p.j.trainer{at}mds.qmw.ac.uk

To establish the factors that modulate circulating CRH-binding protein (CRH-BP) levels, we measured plasma CRH-BP in patients with a variety of endocrine and systemic disorders. CRH-BP was measured by RIA. Young women have higher plasma levels of CRH-BP than young men [females (n = 18), mean ± SEM, 145 ± 7; males (n = 20), 99 ± 6 ng/mL; P < 0.0001], but levels do not fall with the menopause or vary during the menstrual cycle and are unaffected by estrogen replacement therapy. Levels were lower in patients with liver disease than in healthy men (26 ± 3 vs. 99 ± 6; P < 0.0001) and were elevated in chronic renal failure compared to those in healthy women (211 ± 11.2 vs. 145 ± 7; P < 0.01). Levels were unaffected by fasting in men or women (male fasted, 97 ± 11; male fed, 97 ± 8; female fasted, 136 ± 9; female fed, 152 ± 10). Dexamethasone treatment lowered CRH-BP in all subjects (129 ± 8 vs. 111 ± 9; P < 0.003). Similarly, CRH-BP levels were lower in patients with Cushing’s syndrome (all female) than in healthy female controls (median, 82; range, 53–106; vs. median, 142; range, 101–190; P < 0.0001). In Cushing’s patients, an iv bolus of 100 µg human CRH further lowered plasma CRH-BP at 15 min (81 ± 5 vs. 50 ± 4; P < 0.0003).

Plasma levels of CRH-BP are higher in women than men, but this is unrelated to circulating estrogen levels. The low levels in liver disease and the high levels in renal failure support its hepatic origin and the kidneys as the route of clearance from plasma. The ability of glucocorticoids and exogenous CRH to lower plasma CRH-BP levels and of CRH-BP to modulate the bioactivity of circulating CRH suggest that the protein may be an important regulator of circulating CRH or related ligands.

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