Abstract
The aim was to study 3α-androstane-diol glucuronide (3AG) plasma levels and its relationship with 5-ene and 4-ene steroids in children with the benign form of precocious pubarche (precocious adrenarche). Sixty-five children with precocious adrenarche (PA), aged 3.6–8.2 yr (55 girls and 10 males) and 15 normal age-matched children were studied. We evaluated plasma androstenedione (A), dehydroepiandrosterone (DHA), its sulfate (DHA-S), testosterone (T), dihydrotestosterone (DHT), its glucuronide (DHTG), 3α-androstanediol (3Ad) and its glucuronide (3AG) in all subjects. All androgens are expressed as mean±SD. We found significantly higher plasma levels not only in glandular androgens but also in peripheral androgens (A, 2.4±1.5 nM vs 0.79±0.46 nM, p<0.001; DHA, 9.8±4.9 vs2.7±0J6 ng/dl, p<0.001; DHA-S, 3.4±2 μM vs 2.4±0.65 μM, p<0.05; T, 0.74±0.5 nM vs 0.4±0.1 nM, p<0.001; DHT, 0.36±0.13 nM vs 0.12±0.05 nM, p<0.001; 3Ad, 0.13±0.1 nM vs 0.054±0.03 nM, p<0.001; DHTG, 0.5±0.3 nM vs 0.26±0.09 nM p<0.01). As far as the plasma 3AG levels are concerned we found significantly higher values in PA with respect to controls (1.17±0.7 nM vsO.61±0.04 nM, p<0.01), suggesting that 3AG may be considered a marker of skin androgen utilization. 3AG plasma levels correlated better with serum A (p<0.002, r=0.42) and T (p<0.003, r=0.41) than with DHA (p<0.03, r=0.37), suggesting that both 4-ene and 5-ene androgens contribute to its production, but its plasma levels are better correlated with 4-ene than with 5-ene steroids. Furthermore 3AG plasma levels correlated with both 3Ad (p<0.01, r=0.4) and DHTG (p<0.001, r=0.47); no correlation was found with DHT, suggesting that in this condition 3AG may originate, in peripheral tissue either via the unconjugated pathway DHT→3Ad→3AG or via the conjugated pathway DHT→DHTG→3AG.
Similar content being viewed by others
References
Meikle A.W., Stringham Y.D., Wilson D.E., Doman I. 5a-reduced androgens in men and hirsute women: role of adrenals and gonads. J. Clin. Endocrinol. Metab. 45:969, 1979.
Moghissi E., Ablan F., Horton R. Origin of plasma Androstanediol Glucuronide in men. J. Clin. Endocrinol. Metab. 59:417, 1984.
Horton R., Hawks D., Lobo R. 3α, 17p-androstanediol glucuronide in plasma. A new marker of androgen action in idiopathic hir-sutism. J. Clin. Invest. 62:1203, 1982.
Greep N., Hoopes M., Horton R. Androstanediol glucuronide plasma clearance and production rates in normal and hirsute women. J. Clin. Endocrinol. Metab. 62:22, 1986.
Toscano V., Sciarra F., Adamo M.V., Petrangeli E., Foli S., Caiola S., Conti C. Is 3α-androstanediol a marker of peripheral hir-sutism? Acta Endocrinol.(Copenh.) 99:314, 1982.
Abraham G., Chakmakjian Z.H. Plasma steroids in hirsutism. Obstet. Gynecol. 44:171, 1973.
Kirschner M.A., Samojlik E., Small E. Clinical usefulness of plasma androstanediol glu-curonide measurements in women with idiopathic hirsutism. J. Clin. Endocrinol. Metab. 65:597, 1987.
Horton R., Imperato McGinley J. Androstanediol glucuronide (3α-diol) in plasma is a unique marker in disorders of peripheral androgen production and action in male pseudo-hermaphroditism. In: Serio M., Martini L. (Eds.), Sexual Differentiation. Raven Press, New York, 1984, P.261.
Morimoto T., Edmiston A., Horton R. Studies on the origin of androstanediol and an-drostanediol glucuronide in young and elderly men. J. Clin. Endocrinol. Metab. 52:772, 1981.
Horton R., Hawks D., Lobo R. 3α,17β-androstanediol glucuronide in plasma: a marker of androgen action in idiopathic hirsutism. J. Clin. Invest. 69:1203, 1982.
Deslypere J.P., Sayed A., Punjabi U., Verdonck L, Vermeulen A. Plasma 5α-androstane-3α,17β-diol and urinary 5α-androstane-3α,17β-diol glucuronide, parameters of peripheral androgen action: a comparative study. J. Clin. Endocrinol. Metab. 54:386, 1982.
Toscano V. Dihydrotestosterone metabolism. Clin. Endocrinol. Metab. 15:279, 1986.
Ertel N.H., Akgun S., Samojlik E., Kirschner M.A., Imperato-McGinley J. Decreased 3α-androstanediol glucuronide levels in plasma and random urines in male pseudohermaphroditism caused by 5α- reductase deficiency. Metabolism 38:817, 1989.
Mauvais-Jarvis P., Bercovici J.P., Crepy O., Gauthier F. Studies on testosterone metabolism in subjects with testicular feminization syndrome. J. Clin. Invest. 49:31, 1970.
Lobo R.A., Wellington L.P., Gentzschein E., Serafini P.C. Catalino J.A., Paulson R.J., Horton R. Production of 3α-androstanediol glucuronide in hu man genital skin. J. Clin. Endocrinol. Metab. 65:711, 1987.
Gompel A., Wright F., Kuttenn F., Mauvais Jarvis P. Contribution of plasma androstenedione to 5α-an-drostanediol glucuronide in women with idiopathic hirsutism. J. Clin. Endocrinol. Metab. 62:441, 1986.
Greep N., Hooper M., Horton R. Evidence for the role of androstenedione as a pre-cursor for plasma DHT and androstanediol glu-curonide in normal and hirsute women. 67th Annual Meeting of the Endocrine Society 261, 1985.
Giagulli V.A., Verdonck L, Giorgino R., Vermulen A. Precursors of plasma androstanediol and androgen- glucuronides in women. J. Steroid Biochem. 33:935, 1989.
Mauvais Jarvis P., Baulieu E.E. Studies on testosterone metabolism IV. Urinary 5α-and 5β-androstanediols and testosterone glu-curonide from testosterone and dihydroisoandros-terone sulfate in normal people and hirsute women. J. Clin. Endocrinol. Metab. 25:1167, 1965.
Brochu M., Belanger A., Tremblay R. Plasma levels of C-19 steroids and 5α-reduced steroids glucuronides in hyperandrogenic and idio-pathic hirsute women. Fertil. Steril. 43:948, 1987.
Brochu M., Belanger A. Increase in plasma steroid glucuronide levels in men from infancy to adulthood. Fertil. Steril:64:1283, 1987.
Riddick L.M., Garibaldi L.R., Wang M.E., Senne A.R., Klimah O.E., Clark AT., Levine L.S., Oberfield S.E., Pang S. 3α-androstanediol glucuronide in premature and normal pubarche. J. Clin. Endocrinol. Metab 72:46, 1991.
Horton R., Endres D., Galmarini M. Ideal conditions for hydrolysis of androstane 3α, 17(3- diol glucuronide in plasma. J. Clin. Endocrinol. Metab. 59:1027, 1984.
Balducci R., Toscano V. Bioactive and peripheral androgens in prepubertal simple hypertrichosis. Clin. Endocrinol. (Oxf.) 33:407, 1990.
Toscano V., Horton R. Circulating dihydrotestosterone may not reflect pe-ripheral formation. J. Clin. Invest. 79:1653, 1987.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Balducci, R., Finocchi, G., Mangiantini, A. et al. Plasma 3α-androstanediol glucuronide in precocious adrenarche. J Endocrinol Invest 16, 117–121 (1993). https://doi.org/10.1007/BF03347661
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347661