Developmental changes in steroidogenic enzymes in human postnatal adrenal cortex: immunohistochemical studies

Abstract

Adrenarche is considered to occur as a result of intra-adrenal changes in steroidogenic enzymes involved in C19 steroid production. The present study was conducted because developmental changes in steroidogenic enzymes have not been examined well in human postnatal adrenal. Twenty-four specimens of nonpathological human adrenals from 7 months to 62 years retrieved from autopsy files. Immunohistochemistry for P450 side-chain cleavage (P450scc), 17alpha hydroxylase (P450c17), dehydroepiandrosterone sulfotransferase (DHEA-ST), P450 oxidoreductase, cytochrome b5, and 3beta-hydroxysteroid dehydrogenase (3betaHSD) was per-formed in these specimens, and the immuno-intensity was evaluated using CAS 200 computed image analysis system. Immunoreactivity of P450scc was marked in the zona glomerulosa, fasciculata and reticularis in the adrenal glands of all the cases examined. P450c17 and DHEA-ST immunoreactivity was weak in the zona fasciculata and reticularis in the adrenals of age 7 months to 5 years, but thereafter became prominent in the zona reticularis. Immunoreactivity of P450 oxidoreductase and cytochrome b5, components of the electron transfer system hypothesized to regulate the 17-20 lyase activity of P450c17, was weak in all three zones of adrenal cortex from 7 months to 5 years, and became more marked in the zona reticularis after age 5 years. 3betaHSD immunoreactivity was marked in all three zones of the adrenal cortex from 7 months to 8 years but thereafter decreased in the zona reticularis. These data suggest that the human adrenal zona reticularis markedly begins to develop morphologically and functionally at around 5 years of age. The increased level of P450c17, DHEA-ST, P450 oxidoreductase, and cytochrome b5, and the decreased level of 3betaHSD in the reticularis is likely to contribute to increased C19 steroid production during adrenarche.

Adrenarche – physiology, biochemistry and human disease

“…1). In these preadrenarchal infants, there is a poorly developed adrenal reticularis that does not express the enzymes needed to maintain high levels of DHEA-S production (Dhom, 1973;Suzuki et al ., 2000). Dhom (1973) observed that children at about age 3 had adrenals with only focal islands of zona reticularis, while a continuous reticularis did not begin until age 6, coinciding with detectable increases in circulating DHEA-S.…”

“…Although CYP11A is essential for DHEA-S biosynthesis and for adrenarche, all steroid hormone production requires CYP11A as well. In addition, the expression of CYP11A appears to be similar in all three zones of the adrenal cortex, and there are no changes in adrenal reticularis expression of CYP11A seen at adrenarche (Suzuki et al ., 2000). However, as CYP11A (with StAR) is the quantitative regulator of steroidogenesis, alterations in CYP11A activities may contribute to the genesis of premature and /or exaggerated adrenarche.…”

“…Immunoreactivity of 3βHSD was marked in the zona glomerulosa and fasciculata but was almost negative in the zona reticularis. Reproduced, with permission, from Clinical Endocrinology (Suzuki et al, 2000). Lee-Robichaud et al ., 1995;Auchus et al ., 1998).…”

“…These data indicate that adequate amounts of CPR are essential for optimal 17,20-lyase activity. The expression of CPR has been examined in human adrenal glands throughout development (Suzuki et al ., 2000). CPR is expressed in all three adrenal zones, with highest expression in the zona reticularis.…”

Gender and gonadal status differences in zona reticularis expression in marmoset monkey adrenals: Cytochrome b5 localization with respect to cytochrome P450 17,20-lyase activity

“…Recent evidence suggests that adrenarche is a continuous process beginning in utero or at birth (Remer et al 2005). Once again, ZR development of DHEA production by CYP17 in the adrenal cortex is associated with both a reticularis-specific increase in cyt b5 expression while 3β-HSD expression decreases (Endoh et al 1996, Gell et al 1996, Suzuki et al 2000. Adrenarche precedes puberty, and the two processes are thought to be independent.…”