3β-Hydroxysteroid Dehydrogenase/Isomerase in the Fetal Zone and Neocortex of the Human Fetal Adrenal Gland*

Abstract

The fetal zone of the human fetal adrenal (HFA) gland is established to have decreased 3 beta-hydroxysteroid dehydrogenase/delta 4-5 isomerase (3 beta HSD) activity compared to the neocortex or definitive zone. 3 beta HSD activity, however, can be induced in primary cell culture through treatment with ACTH. Therefore, the HFA with two distinct steroidogenic zones with differences in 3 beta HSD activity as well as the capacity to increase 3 beta HSD activity in response to ACTH provides an excellent model to study the regulation of this enzyme. The presence of 3 beta HSD in the fetal and neocortex zones of the HFA was examined using a polyclonal antibody raised against purified human placental microsomal 3 beta HSD. After homogenates of the fetal and neocortical zones of the HFA were electrophoresed on a sodium dodecyl sulfate-polyacrylamide gel and immunoblotted, the presence of the 3 beta HSD protein with a molecular size of 45 kDa could be demonstrated only in the neocortical zone. ACTH treatment (greater than 2 days) of fetal and neocortical zone explant cultures produced increases in cortisol secretion associated with the respective levels of immunodetectable 3 beta HSD protein. Cortisol and dehydroepiandrosterone sulfate were the respective principal steroid products of neocortical and fetal zone explants. After ACTH treatment, immunodetectable 3 beta HSD was induced to a greater magnitude in the neocortex. These findings provide evidence that the lack of 3 beta HSD activity in the fetal zone, previously considered to be the result of the presence of an endogenous inhibitor, is due to an absence of the protein in this portion of the gland. The lack or minimal expression of 3 beta HSD in the fetal zone of HFA may be due to the action (or lack thereof) of a tissue-specific factor regulating the synthesis of 3 beta HSD.

Developmental expression of and effect of betamethasone on the messenger ribonucleic acid levels for peptide growth factors in the baboon fetal adrenal gland

“…This developmental pattern of IGFBP-2 and bFGF mRNA expression is similar to that previously shown for 3 -HSD (Albrecht et al 1996, Aberdeen et al 1997, the expression of which is confined to the emerging transitional and definitive zones (Doody et al 1990, Mesiano et al 1993. Although IGFBP-2 was expressed throughout the fetal adrenal cortex of the rhesus monkey (Coulter et al 1996), it is possible that IGFBP-2 and/or bFGF, like 3 -HSD, become expressed in greater abundance in the transitional zone of the baboon fetal adrenal very late in gestation.…”

“…Adrenal 3 -HSD immunocytochemistry and histology A relatively wide band of immunocytochemical staining for 3 -HSD, an enzyme expressed specifically within the definitive and transitional zones of the cortex (Doody et al 1990, Coulter et al 1996, was evident in the fetal adrenal of untreated baboons late in gestation (Fig. 5A).…”

Cortisol is transported by the multidrug resistance gene product P-glycoprotein

“…We recently have shown that the cells of the foetal zone of the foetal adrenal cortex do not express Pgp, while cells of the definitive zone or neocortex of the foetal adrenal cortex clearly expressed Pgp (van Kalken et al, 1992). Furthermore, while the foetal zone cells are deficient in the enzyme 3p-hydroxysteroid dehydrogenase (3p-OHSD) and hence in mineral-and glucocorticoid production (Doody et al, 1990;Preston Nelson, 1990), the Pgp expressing neocortex has markedly higher 3P-OHSD activity and capacity to synthesise cortisol (Doody et al, 1990). …”

Regulation of the adrenal androgen biosynthesis

“…The human adrenal produces DHEA at high levels within the fetal adrenal and in the zona reticularis of the adult adrenal. Both of these tissues express low levels of HSD3B2 mRNA and protein [6,[27][28][29][30][31][32]. Thus, a detailed understanding of the mechanisms that regulate HSD3B2 expression would help in efforts to understand adrenal physiology.…”