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Department of Molecular Endocrinology, University College and Middlesex School of Medicine London, W1N 8AA, United Kingdom
Correspondence: Address requests for reprints to: Dr. Roger Ekins, Department of Molecular Endocrinology, University College of Middlesex, School of Medicine, Mortimer Street, London WIN 8AA, United Kingdom.
Abstract
I. Physiological and Clinical Rationale of Free Hormone Measurement; Free Hormones in Vivo and the Validity of the Free Hormone Hypothesis of Hormone Action: It is widely accepted that, in the case of those hormones which exist in blood in free and protein-bound forms, the free hormone concentration measured under equilibrium conditions in vitro constitutes the essential determinant of the hormone's physiological activity. This concept, termed the "free hormone hypothesis" of hormone action, derives from the observation that in subjects in whom the concentrations of binding proteins (and, concomitantly, of bound hormone) are "abnormal," hormonal effects correlate closely with the free hormone concentration, not the bound. This observation, together with other evidence, underlies the general belief that only hormone in free form is transported into target tissues. However, the accuracy of serum free hormone measurements which led to, and now sustain, the free hormone hypothesis has been uncertain; furthermore, a demonstration that only free hormone traverses capillary walls and penetrates into cells does not establish that the bound hormone level is without influence on the rate of hormone delivery, and that the hypothesis is therefore correct. The validity of the hypothesis has not, in short, been established beyond doubt, nor does the serum free hormone level seen in vitro necessarily provide a true indication of the hormone's availability to all organs in the body. Since, however, this concept underlies the clinical use of free hormone measurements, it is relevant to examine the somewhat insecure physicochemical foundations on which it rests.
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