The steroid metabolome of adrenarche - PubMed (original) (raw)

Review

. 2012 Aug;214(2):133-43.

doi: 10.1530/JOE-12-0183. Epub 2012 Jun 19.

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Review

The steroid metabolome of adrenarche

Juilee Rege et al. J Endocrinol. 2012 Aug.

Abstract

Adrenarche is an endocrine developmental process whereby humans and select nonhuman primates increase adrenal output of a series of steroids, especially DHEA and DHEAS. The timing of adrenarche varies among primates, but in humans serum levels of DHEAS are seen to increase at around 6 years of age. This phenomenon corresponds with the development and expansion of the zona reticularis of the adrenal gland. The physiological phenomena that trigger the onset of adrenarche are still unknown; however, the biochemical pathways leading to this event have been elucidated in detail. There are numerous reviews examining the process of adrenarche, most of which have focused on the changes within the adrenal as well as the phenotypic results of adrenarche. This article reviews the recent and past studies that show the breadth of changes in the circulating steroid metabolome that occur during the process of adrenarche.

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Figures

Figure 1

Figure 1

Serum DHEA and DHEAS levels before and after the onset of human adrenarche. Based on steroid levels from de Peretti and Forest 1976, 1978.

Figure 2

Figure 2

Adrenal-derived C19 steroids act as precursors for the production of more potent androgens in peripheral tissues including hair follicles, genital skin and prostate. The classical pathway for bioactive androgen synthesis as well as a proposed alternative pathway using 11β-hydroxyandrostenedione (11OHA) is shown. A, androstenedione; T, testosterone; DHT, dihydrotestosterone; 11OHT, 11β-hydroxytestosterone; 5,11OHT, 5α,11β-hydroxytestosterone; 17βHSDs; 17β-hydroxysteroid dehydrogenases (type 5 or type 3)

Figure 3

Figure 3

DHEAS and expansion of the adrenal reticularis. (A) The relationship between the development of the ZR and plasma DHEAS levels (Dhom 1973; Reiter et al. 1977). (B) The morphological development of the adrenal zona reticularis depicting the appearance of focal islands of reticular tissue and a continuous ‘functional’ ZR (17).

Figure 4

Figure 4

(A) Steroid pathways for biosynthesis of adrenocortical steroids. StAR, steroidogenic acute regulatory protein; CYP11A1, cytochrome P450 cholesterol side-chain cleavage; CYP17,17α-hydroxylase/17,20-lyase; HSD3B2, 3β-hydroxysteroid dehydrogenase type 2; CYB5, cytochrome b5; HSD17B5, 17β-hydroxysteroid dehydrogenase type 5; SULT2A1, steroid sulfotransferase type 2A1; CYP11B1, 11β-hydroxylase. (B) Immunohistochemical examination of HSD3B2 expression in the human adrenal cortex from a four year old child (pre adrenarche) and a nine year old child (post adrenarche). As observed in these micrographs the post adrenarche adrenal is characterized by the expansion of a HSD3B3 deficient ZR.

Figure 4

Figure 4

(A) Steroid pathways for biosynthesis of adrenocortical steroids. StAR, steroidogenic acute regulatory protein; CYP11A1, cytochrome P450 cholesterol side-chain cleavage; CYP17,17α-hydroxylase/17,20-lyase; HSD3B2, 3β-hydroxysteroid dehydrogenase type 2; CYB5, cytochrome b5; HSD17B5, 17β-hydroxysteroid dehydrogenase type 5; SULT2A1, steroid sulfotransferase type 2A1; CYP11B1, 11β-hydroxylase. (B) Immunohistochemical examination of HSD3B2 expression in the human adrenal cortex from a four year old child (pre adrenarche) and a nine year old child (post adrenarche). As observed in these micrographs the post adrenarche adrenal is characterized by the expansion of a HSD3B3 deficient ZR.

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