Bioavailability of albumin-bound testosterone

Andrea Manni, William M. Pardridge, William Cefalu, Bruce C. Nisula, C. Wayne Bardin, Steven J. Santner, Richard J. Santen

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

The unbound fraction of plasma testosterone (T) can freely enter tissues, whereas the bioavailability of the albumin-bound T is controversial. A clinical observation in hirsute women receiving spironolactone suggested an experimental paradigm to test the effect of albumin binding on T bioavailability. We found an increase in the non-T-estrogen-binding globulin-bound fraction of plasma T in women from 24.1 ± 3.9% to 42.0 ± 8.1% (±SEM) while they received spironolactone. Computer modeling indicated that the absolute increase in the albumin-bound T concentration would be about 22.4-fold greater than that in the unbound T concentration (the ratio of albuminbound to free T remaining virtually constant) because of the binding of T to albumin. We reasoned that the addition of graded amounts of spironolactone and its metabolites to plasma would provide a means to increase the albumin-bound T concentration appreciably. We evaluated the biological effects of this perturbation of T transport by spironolactone and its metabolites in a bioassay system using the Oldendorf technique. Bioavailable T increased proportionately with increments in free and albumin-bound T (r = 0.85; P < 0.01). A major portion of the albumin-bound T (i.e. 55%) entered tissues under all conditions; the amount that was bioavailable vastly exceeded the amount of T that was unbound in the injected samples. An index of the amount of bioavailable T can be determined using the ammonium sulfate precipitation technique, as the percentage of non- T-estrogen-binding globulin-bound T in vitro correlated well with T bioavailability in vitro (r = 0.86; P < 0.01). These studies support the conclusion that albumin-bound T is biologically important.(J Clin Endocrinol Metab 61: 705, 1985).

Original languageEnglish (US)
Pages (from-to)705-710
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume61
Issue number4
DOIs
StatePublished - Oct 1985

Fingerprint

Biological Availability
Testosterone
Albumins
Spironolactone
Globulins
Metabolites
Plasmas
Estrogens
Tissue
Bioassay
Ammonium Sulfate
Biological Assay
Observation
Scanning electron microscopy

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Manni, A., Pardridge, W. M., Cefalu, W., Nisula, B. C., Bardin, C. W., Santner, S. J., & Santen, R. J. (1985). Bioavailability of albumin-bound testosterone. Journal of Clinical Endocrinology and Metabolism, 61(4), 705-710. https://doi.org/10.1210/jcem-61-4-705
Manni, Andrea ; Pardridge, William M. ; Cefalu, William ; Nisula, Bruce C. ; Bardin, C. Wayne ; Santner, Steven J. ; Santen, Richard J. / Bioavailability of albumin-bound testosterone. In: Journal of Clinical Endocrinology and Metabolism. 1985 ; Vol. 61, No. 4. pp. 705-710.
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abstract = "The unbound fraction of plasma testosterone (T) can freely enter tissues, whereas the bioavailability of the albumin-bound T is controversial. A clinical observation in hirsute women receiving spironolactone suggested an experimental paradigm to test the effect of albumin binding on T bioavailability. We found an increase in the non-T-estrogen-binding globulin-bound fraction of plasma T in women from 24.1 ± 3.9{\%} to 42.0 ± 8.1{\%} (±SEM) while they received spironolactone. Computer modeling indicated that the absolute increase in the albumin-bound T concentration would be about 22.4-fold greater than that in the unbound T concentration (the ratio of albuminbound to free T remaining virtually constant) because of the binding of T to albumin. We reasoned that the addition of graded amounts of spironolactone and its metabolites to plasma would provide a means to increase the albumin-bound T concentration appreciably. We evaluated the biological effects of this perturbation of T transport by spironolactone and its metabolites in a bioassay system using the Oldendorf technique. Bioavailable T increased proportionately with increments in free and albumin-bound T (r = 0.85; P < 0.01). A major portion of the albumin-bound T (i.e. 55{\%}) entered tissues under all conditions; the amount that was bioavailable vastly exceeded the amount of T that was unbound in the injected samples. An index of the amount of bioavailable T can be determined using the ammonium sulfate precipitation technique, as the percentage of non- T-estrogen-binding globulin-bound T in vitro correlated well with T bioavailability in vitro (r = 0.86; P < 0.01). These studies support the conclusion that albumin-bound T is biologically important.(J Clin Endocrinol Metab 61: 705, 1985).",
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Manni, A, Pardridge, WM, Cefalu, W, Nisula, BC, Bardin, CW, Santner, SJ & Santen, RJ 1985, 'Bioavailability of albumin-bound testosterone', Journal of Clinical Endocrinology and Metabolism, vol. 61, no. 4, pp. 705-710. https://doi.org/10.1210/jcem-61-4-705

Bioavailability of albumin-bound testosterone. / Manni, Andrea; Pardridge, William M.; Cefalu, William; Nisula, Bruce C.; Bardin, C. Wayne; Santner, Steven J.; Santen, Richard J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 61, No. 4, 10.1985, p. 705-710.

Research output: Contribution to journalArticle

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AU - Manni, Andrea

AU - Pardridge, William M.

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N2 - The unbound fraction of plasma testosterone (T) can freely enter tissues, whereas the bioavailability of the albumin-bound T is controversial. A clinical observation in hirsute women receiving spironolactone suggested an experimental paradigm to test the effect of albumin binding on T bioavailability. We found an increase in the non-T-estrogen-binding globulin-bound fraction of plasma T in women from 24.1 ± 3.9% to 42.0 ± 8.1% (±SEM) while they received spironolactone. Computer modeling indicated that the absolute increase in the albumin-bound T concentration would be about 22.4-fold greater than that in the unbound T concentration (the ratio of albuminbound to free T remaining virtually constant) because of the binding of T to albumin. We reasoned that the addition of graded amounts of spironolactone and its metabolites to plasma would provide a means to increase the albumin-bound T concentration appreciably. We evaluated the biological effects of this perturbation of T transport by spironolactone and its metabolites in a bioassay system using the Oldendorf technique. Bioavailable T increased proportionately with increments in free and albumin-bound T (r = 0.85; P < 0.01). A major portion of the albumin-bound T (i.e. 55%) entered tissues under all conditions; the amount that was bioavailable vastly exceeded the amount of T that was unbound in the injected samples. An index of the amount of bioavailable T can be determined using the ammonium sulfate precipitation technique, as the percentage of non- T-estrogen-binding globulin-bound T in vitro correlated well with T bioavailability in vitro (r = 0.86; P < 0.01). These studies support the conclusion that albumin-bound T is biologically important.(J Clin Endocrinol Metab 61: 705, 1985).

AB - The unbound fraction of plasma testosterone (T) can freely enter tissues, whereas the bioavailability of the albumin-bound T is controversial. A clinical observation in hirsute women receiving spironolactone suggested an experimental paradigm to test the effect of albumin binding on T bioavailability. We found an increase in the non-T-estrogen-binding globulin-bound fraction of plasma T in women from 24.1 ± 3.9% to 42.0 ± 8.1% (±SEM) while they received spironolactone. Computer modeling indicated that the absolute increase in the albumin-bound T concentration would be about 22.4-fold greater than that in the unbound T concentration (the ratio of albuminbound to free T remaining virtually constant) because of the binding of T to albumin. We reasoned that the addition of graded amounts of spironolactone and its metabolites to plasma would provide a means to increase the albumin-bound T concentration appreciably. We evaluated the biological effects of this perturbation of T transport by spironolactone and its metabolites in a bioassay system using the Oldendorf technique. Bioavailable T increased proportionately with increments in free and albumin-bound T (r = 0.85; P < 0.01). A major portion of the albumin-bound T (i.e. 55%) entered tissues under all conditions; the amount that was bioavailable vastly exceeded the amount of T that was unbound in the injected samples. An index of the amount of bioavailable T can be determined using the ammonium sulfate precipitation technique, as the percentage of non- T-estrogen-binding globulin-bound T in vitro correlated well with T bioavailability in vitro (r = 0.86; P < 0.01). These studies support the conclusion that albumin-bound T is biologically important.(J Clin Endocrinol Metab 61: 705, 1985).

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Manni A, Pardridge WM, Cefalu W, Nisula BC, Bardin CW, Santner SJ et al. Bioavailability of albumin-bound testosterone. Journal of Clinical Endocrinology and Metabolism. 1985 Oct;61(4):705-710. https://doi.org/10.1210/jcem-61-4-705