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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1981 Apr;67(4):1177–1182. doi: 10.1172/JCI110132

The developmental changes in plasma adrenal androgens during infancy and adrenarche are associated with changing activities of adrenal microsomal 17-hydroxylase and 17,20-desmolase.

R J Schiebinger, B D Albertson, F G Cassorla, D W Bowyer, G W Geelhoed, G B Cutler Jr, D L Loriaux
PMCID: PMC370679  PMID: 6970754

Abstract

The plasma concentrations of dehydroepiandrosterone, androstenedione, and dehydroepiandrosterone sulfate decrease during the first year of life, remain low during childhood, and then increase during adrenarche. To determine whether alterations in adrenal enzyme activity might explain the changing secretory pattern of the adrenal androgens, we measured human adrenal microsomal 3 beta-hydroxysteroid dehydrogenase-isomerase, 17,20-desmolase, 17-hydroxylase, and 21-hydroxylase activities. 12 adrenals from individuals aged 3 mo to 60 yr were studied. The patients were divided into three groups based upon the age of the patient when the adrenal glands were obtained: group 1, infants aged 3--8 mo (n = 3); group 2, preadrenarchal or early adrenarchal children aged 2--9 yr (n = 4); and group 3, adults aged 20--60 yr (n = 5). The mean activity of the 17,20-desmolase, 17-hydroxylase, and 21-hydroxylase fell by 50% and that of 3 beta-hydroxysteroid dehydrogenase-isomerase activity rose 80% from group 1 to 2. A fourfold increase in 17,20-desmolase (P less than 0.002) and 17-hydroxylase (P less than 0.001) activity and a doubling in 21-hydroxylase activity (P less than 0.005) occurred between groups 2 and 3. We conclude that the decline in plasma adrenal androgens after birth appears to be associated with a rise in 3 beta-hydroxysteroid dehydrogenase-isomerase and a fall in 17,20-desmolase and 17-hydroxylase activity. The subsequent increase in plasma adrenal androgen concentration during adrenarche is coincident with a rise in 17,20-desmolase and 17-hydroxylase activity.

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Selected References

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  1. Abraham G. E., Swerdloff R., Tulchinsky D., Odell W. D. Radioimmunoassay of plasma progesterone. J Clin Endocrinol Metab. 1971 May;32(5):619–624. doi: 10.1210/jcem-32-5-619. [DOI] [PubMed] [Google Scholar]
  2. Betz G., Michels D. Steroid 17,20-lyase: the effect of detergents on enzymic activity and microsomal composition. Steroids. 1973 Jun;21(6):785–800. doi: 10.1016/0039-128x(73)90121-9. [DOI] [PubMed] [Google Scholar]
  3. Cameron E. H., Jones T., Jones D., Anderson A. B., Griffiths K. Further studies on the relationship between C19- and C21-steroid synthesis in the human adrenal gland. J Endocrinol. 1969 Oct;45(2):215–230. doi: 10.1677/joe.0.0450215. [DOI] [PubMed] [Google Scholar]
  4. Cutler G. B., Jr, Glenn M., Bush M., Hodgen G. D., Graham C. E., Loriaux D. L. Adrenarche: a survey of rodents, domestic animals, and primates. Endocrinology. 1978 Dec;103(6):2112–2118. doi: 10.1210/endo-103-6-2112. [DOI] [PubMed] [Google Scholar]
  5. Dhom G. The prepuberal and puberal growth of the adrenal (adrenarche). Beitr Pathol. 1973 Dec;150(4):357–377. doi: 10.1016/s0005-8165(73)80086-1. [DOI] [PubMed] [Google Scholar]
  6. Ducharme J. R., Forest M. G., De Peretti E., Sempé M., Collu R., Bertrand J. Plasma adrenal and gonadal sex steroids in human pubertal development. J Clin Endocrinol Metab. 1976 Mar;42(3):468–476. doi: 10.1210/jcem-42-3-468. [DOI] [PubMed] [Google Scholar]
  7. Forest M. G. Age-related response of plasma testosterone, delta 4-androstenedione, and cortisol to adrenocorticotropin in infants, children, and adults. J Clin Endocrinol Metab. 1978 Nov;47(5):931–937. doi: 10.1210/jcem-47-5-931. [DOI] [PubMed] [Google Scholar]
  8. Forest M. G., Cathiard A. M. Pattern of plasma testosterone and delta4-androstenedione in normal newborns: Evidence for testicular activity at birth. J Clin Endocrinol Metab. 1975 Nov;41(5):977–980. doi: 10.1210/jcem-41-5-977. [DOI] [PubMed] [Google Scholar]
  9. Goldman A. S. Inhibition of 3-beta-hydroxysteroid dehydrogenase from Pseudomonas testosteroni by various estrogenic and progestinic steroids. J Clin Endocrinol Metab. 1967 Mar;27(3):320–324. doi: 10.1210/jcem-27-3-320. [DOI] [PubMed] [Google Scholar]
  10. Hopper B. R., Yen S. S. Circulating concentrations of dehydroepiandrosterone and dehydroepiandrosterone sulfate during puberty. J Clin Endocrinol Metab. 1975 Mar;40(3):458–461. doi: 10.1210/jcem-40-3-458. [DOI] [PubMed] [Google Scholar]
  11. Kenny F. M., Preeyasombat C., Migeon C. J. Cortisol production rate. II. Normal infants, children, and adults. Pediatrics. 1966 Jan;37(1):34–42. [PubMed] [Google Scholar]
  12. Korth-Schutz S., Levine L. S., New M. I. Dehydroepiandrosterone sulfate (DS) levels, a rapid test for abnormal adrenal androgen secretion. J Clin Endocrinol Metab. 1976 Jun;42(6):1005–1013. doi: 10.1210/jcem-42-6-1005. [DOI] [PubMed] [Google Scholar]
  13. Korth-Schutz S., Levine L. S., New M. I. Evidence for the adrenal source of androgens in precocious adrenarche. Acta Endocrinol (Copenh) 1976 Jun;82(2):342–352. doi: 10.1530/acta.0.0820342. [DOI] [PubMed] [Google Scholar]
  14. Korth-Schutz S., Levine L. S., New M. I. Serum androgens in normal prepubertal and pubertal children and in children with precocious adrenarche. J Clin Endocrinol Metab. 1976 Jan;42(1):117–124. doi: 10.1210/jcem-42-1-117. [DOI] [PubMed] [Google Scholar]
  15. LANMAN J. T. The fetal zone of the adrenal gland: its developmental course, comparative anatomy, and possible physiologic functions. Medicine (Baltimore) 1953 Dec;32(4):389–430. doi: 10.1097/00005792-195312000-00001. [DOI] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Lee P. A., Kowarski A., Migeon C. J., Blizzard R. M. Lack of correlation between gonadotropin and adrenal androgen levels in agonadal children. J Clin Endocrinol Metab. 1975 Apr;40(4):664–669. doi: 10.1210/jcem-40-4-664. [DOI] [PubMed] [Google Scholar]
  18. McCune R. W., Roberts S., Young P. L. Competitive inhibition of adrenal delta 5-3 beta-hydroxysteroid dehydrogenase and delta 5-3-ketosteroid isomerase activities by adenosine 3',5'-monophosphate. J Biol Chem. 1970 Aug 10;245(15):3859–3867. [PubMed] [Google Scholar]
  19. Menard R. H., Bartter F. C., Gillette J. R. Spironolactone and cytochrome P-450: impairment of steroid 21-hydroxylation in the adrenal cortex. Arch Biochem Biophys. 1976 Apr;173(2):395–402. doi: 10.1016/0003-9861(76)90277-0. [DOI] [PubMed] [Google Scholar]
  20. OFSTAD J., LAMVIK J., STOA K. F., EMBERLAND R. Adrenal steroid synthesis in amyloid degeneration localised exclusively to the zona reticularis. Acta Endocrinol (Copenh) 1961 Jul;37:321–328. doi: 10.1530/acta.0.0370321. [DOI] [PubMed] [Google Scholar]
  21. Reiter E. O., Fuldauer V. G., Root A. W. Secretion of the adrenal androgen, dehydroepiandrosterone sulfate, during normal infancy, childhood, and adolescence, in sick infants, and in children with endocrinologic abnormalities. J Pediatr. 1977 May;90(5):766–770. doi: 10.1016/s0022-3476(77)81244-4. [DOI] [PubMed] [Google Scholar]
  22. Rosenfield R. L., Eberlein W. R. Plasma 17-ketosteroid levels during adolescence. J Pediatr. 1969 Jun;74(6):932–936. doi: 10.1016/s0022-3476(69)80228-3. [DOI] [PubMed] [Google Scholar]
  23. Sobrinho L. G., Kase N. G., Grunt J. A. Changes in adrenocortisol function of patients with gonadal dysgenesis after treatment with estrogen. J Clin Endocrinol Metab. 1971 Jul;33(1):110–114. doi: 10.1210/jcem-33-1-110. [DOI] [PubMed] [Google Scholar]
  24. Tan S. Y., Murphy B. E. Plasma 17alpha hydroxyprogesterone: an improved radioassay method. Steroids. 1975 Feb;25(2):283–284. doi: 10.1016/s0039-128x(75)90203-2. [DOI] [PubMed] [Google Scholar]
  25. Warne G. L., Carter J. N., Faiman C., Reyes F. I., Winter J. S. Hormonal changes in girls with precocious adrenarche: a possible role for estradiol or prolactin. J Pediatr. 1978 May;92(5):743–747. doi: 10.1016/s0022-3476(78)80141-3. [DOI] [PubMed] [Google Scholar]
  26. de Peretti E., Forest M. G. Pattern of plasma dehydroepiandrosterone sulfate levels in humans from birth to adulthood: evidence for testicular production. J Clin Endocrinol Metab. 1978 Sep;47(3):572–577. doi: 10.1210/jcem-47-3-572. [DOI] [PubMed] [Google Scholar]
  27. de Peretti E., Forest M. G. Unconjugated dehydroepiandrosterone plasma levels in normal subjects from birth to adolescence in human: the use of a sensitive radioimmunoassay. J Clin Endocrinol Metab. 1976 Nov;43(5):982–991. doi: 10.1210/jcem-43-5-982. [DOI] [PubMed] [Google Scholar]

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