Background: Relative adrenocortical insufficiency is often seen in sick premature newborns. As the human fetal adrenal cortex does not express the 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme before about 23 weeks of gestation, we hypothesized that this enzymatic step may be rate limiting in cortisol synthesis in premature infants of less than 28 weeks postmenstrual age at birth. Methods: We measured cord, first day (D0) and median fourth day (D4) serum 17-OH-pregnenolone (17-OHPreg), 17-OH-progesterone (17-OHProg), 11-deoxycortisol, cortisol (F) and dehydroepiandrosterone sulphate concentrations and calculated the substrate/product ratios in 67 infants with gestational age 23.6–33.1 weeks. Results: The mean 17-OHPreg/17-OHProg ratio as a marker of 3β-HSD activity did not differ between the gestational age groups (gestational age <28 vs. ≧28 weeks: 0.40 vs. 0.48, p = 0.52 for cord, 3.1 vs. 2.4, p = 0.25 for D0, and 1.6 vs. 1.9, p = 0.62 for D4). In addition, the 17-OHPreg/17-OHProg ratio did not differ between the infants in the lowest F tertile compared to those in the highest F tertile group, and the serum 17-OHPreg and 17-OHProg concentrations were parallel with the respective F concentrations. Conclusion: We did not find evidence of significant immaturity in adrenal 3β-HSD activity in preterm infants between 24 and 28 weeks of gestation.

1.
Mesiano S, Jaffe RB: Developmental and functional biology of the primate fetal adrenal cortex. Endocr Rev 1997;18:378–403.
2.
Doody KM, Carr BR, Rainey WE, Byrd W, Murry BA, Strickler RC, Thomas JL, Mason JI: 3 beta-hydroxysteroid dehydrogenase/isomerase in the fetal zone and neocortex of the human fetal adrenal gland. Endocrinology 1990;126:2487–2492.
3.
Voutilainen R, Ilvesmäki V, Miettinen PJ: Low expression of 3 beta-hydroxy-5-ene steroid dehydrogenase gene in human fetal adrenals in vivo; adrenocorticotropin and protein kinase C-dependent regulation in adrenocortical cultures. J Clin Endocrinol Metab 1991;72:761–767.
4.
Narasaka T, Suzuki T, Moriya T, Sasano H: Temporal and spatial distribution of corticosteroidogenic enzymes immunoreactivity in developing human adrenal. Mol Cell Endocrinol 2001;174:111–120.
5.
Goto M, Piper Hanley K, Marcos J, Wood PJ, Wright S, Postle AD, Cameron IT, Mason JI, Wilson DI, Hanley NA: In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development. J Clin Invest 2006;116:953–960.
6.
Voutilainen R, Kahri AI, Salmenperä M: The effects of progesterone, pregnenolone, estriol, ACTH and HCG on steroid secretion of cultured human fetal adrenals. J Steroid Biochem 1979;10:695–700.
7.
Voutilainen R, Miller WL: Developmental expression of genes for the steroidogenic enzymes P450scc (20,22-desmolase), P450c17 (17 alpha-hydroxylase/17,20-lyase), and P450c21 (21-hydroxylase) in the human fetus. J Clin Endocrinol Metab 1986;63:1145–1150.
8.
Ilvesmäki V, Voutilainen R: Interaction of phorbol ester and adrenocorticotropin in the regulation of steroidogenic P450 genes in human fetal and adult adrenal cell cultures. Endocrinology 1991;128:1450–1458.
9.
Fernandez EF, Watterberg KL: Relative adrenal insufficiency in the preterm and term infant. J Perinatol 2009;29:544–549.
10.
Thomas S, Murphy JF, Dyas J, Ryalls M, Hughes IA: Response to ACTH in the newborn. Arch Dis Child 1986;61:57–60.
11.
Hanna CE, Keith LD, Colasurdo MA, Buffkin DC, Laird MR, Mandel SH, Cook DM, LaFranchi SH, Reynolds JW: Hypothalamic pituitary adrenal function in the extremely low birth weight infant. J Clin Endocrinol Metab 1993;76:384–387.
12.
Ng PC, Lam CW, Lee CH, Ma KC, Fok TF, Chan IH, Wong E: Reference ranges and factors affecting the human corticotrophin-releasing hormone test in preterm, very low birth weight infants. J Clin Endocrinol Metab 2002;87:4621–4628.
13.
Watterberg KL, Shaffer ML, Garland JS, Thilo EH, Mammel MC, Couser RJ, Aucott SW, Leach CL, Cole CH, Gerdes JS, Rozycki HJ, Backstrom C: Effect of dose on response to adrenocorticotropin in extremely low birth weight infants. J Clin Endocrinol Metab 2005;90:6380–6385.
14.
Fernandez EF, Montman R, Watterberg KL: ACTH and cortisol response to critical illness in term and late preterm newborns. J Perinatol 2008;28:797–802.
15.
Lee MM, Rajagopalan L, Berg GJ, Moshang T Jr: Serum adrenal steroid concentrations in premature infants. J Clin Endocrinol Metab 1989;69:1133–1136.
16.
Hingre RV, Gross SJ, Hingre KS, Mayes DM, Richman RA: Adrenal steroidogenesis in very low birth weight preterm infants. J Clin Endocrinol Metab 1994;78:266–270.
17.
al Saedi S, Dean H, Dent W, Cronin C: Reference ranges for serum cortisol and 17-hydroxyprogesterone levels in preterm infants. J Pediatr 1995;126:985–987.
18.
Watterberg KL, Gerdes JS, Cook KL: Impaired glucocorticoid synthesis in premature infants developing chronic lung disease. Pediatr Res 2001;50:190–195.
19.
Nykänen P, Anttila E, Heinonen K, Hallman M, Voutilainen R: Early hypoadrenalism in premature infants at risk for bronchopulmonary dysplasia or death. Acta Paediatr 2007;96:1600–1605.
20.
Pihkala J, Hakala T, Voutilainen P, Raivio K: Characteristic of recent fetal growth curves in Finland. Duodecim 1989;105:1540–1546. (Article in Finnish.)
21.
Sippell WG, Bidlingmaier F, Becker H, Brünig T, Dörr H, Hahn H, Golder W, Hollmann G, Knorr D: Simultaneous radioimmunoassay of plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11- deoxycortisol, cortisol and cortisone. J Steroid Biochem 1978;9:63–74.
22.
Riepe FG, Wonka S, Partsch CJ, Sippell WG: Automated chromatographic system for the simultaneous measurement of plasma pregnenolone and 17-hydroxypregnenolone by radioimmunoassay. J Chromatogr B Biomed Sci Appl 2001;763:99–106.
23.
Doerr HG, Sippell WG, Versmold HT, Bidlingmaier F, Knorr D: Plasma mineralocorticoids, glucocorticoids, and progestins in premature infants: longitudinal study during the first week of life. Pediatr Res 1988;23:525–529.
24.
Riepe FG, Mahler P, Sippell WG, Partsch CJ: Longitudinal study of plasma pregnenolone and 17-hydroxypregnenolone in full-term and preterm neonates at birth and during the early neonatal period. J Clin Endocrinol Metab 2002;87:4301–4306.
25.
Dörr HG, Versmold HT, Sippell WG, Bidlingmaier F, Knorr D: Antenatal betamethasone therapy: effects on maternal, fetal, and neonatal mineralocorticoids, glucocorticoids, and progestins. J Pediatr 1986;108:990–993.
26.
Doerr HG, Versmold HT, Bidlingmaier F, Sippell WG: Adrenocortical steroids in small-for-gestational-age term infants during the early neonatal period. Pediatr Res 1989;25:115–118.
27.
Gatelais F, Berthelot J, Beringue F, Descamps P, Bonneau D, Limal JM, Coutant R: Effect of single and multiple courses of prenatal corticosteroids on 17-hydroxyprogesterone levels: implication for neonatal screening of congenital adrenal hyperplasia. Pediatr Res 2004;56:701–705.
28.
Terrone DA, Smith LG Jr, Wolf EJ, Uzbay LA, Sun S, Miller RC: Neonatal effects and serum cortisol levels after multiple courses of maternal corticosteroids. Obstet Gynecol 1997;90:819–823.
29.
Bolt RJ, van Weissenbruch MM, Lafeber HN, Delemarre-van de Waal HA: Development of the hypothalamic-pituitary-adrenal axis in the fetus and preterm infant. J Pediatr Endocrinol Metab 2002;15:759–769.
30.
Arafah BM: Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab 2006;91:3725–3745.
31.
Kari AM, Raivio KO, Stenman UH, Voutilainen R: Serum cortisol, dehydroepiandrosterone sulphate, and steroid-binding globulins in preterm neonates: effect of gestational age and dexamethasone therapy. Pediatr Res 1996;40:319–324.
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