3β-hydroxysteroid dehydrogenase/isomerase in the fetal zone and neocortex of the human fetal adrenal gland

The fetal zone of the human fetal adrenal (HFA) gland is established to have decreased 30-hydroxysteroid dehydrogenase/Δ^4-5isomerase (3βHSD) activity compared to the neocortex or definitive zone. 3βHSD activity, however, can be induced in primary cell culture through treatment with ACTH. Therefore, the HFA with two distinct steroidogenic zones with differences in 3βHSD activity as well as the capacity to increase 3βHSD activity in response to ACTH provides an excellent model to study the regulation of this enzyme. The presence of 3βHSD in the fetal and neocortex zones of the HFA was examined using a polyclonal antibody raised against purified human placental microsomal 3βHSD. After homogenstes of the fetal and neocortical zones of the HFA were electrophoresed on a sodium dodecyl sulfate-polyacrylamide gel and immunoblotted, the presence of the 3βHSD protein with a molecular size of 45 kDa could be demonstrated only in the neocortical zone. ACTH treatment (>2 days) of fetal and neocortical zone explant cultures produced increases in Cortisol secretion associated with the respective levels of immunodetectable 3βHSD protein. Cortisol and dehydroepiandrosterone sulfate were the respective principal steroid products of neocortical and fetal zone explants. After ACTH treatment, immunodetectable 3βHSD was induced to a greater magnitude in the neocortex. These findings provide evidence that the lack of 3βHSD 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 3βHSD in the fetal zone of HFA may be due to the action (or lack thereof) of a tissue-specific factor regulating the synthesis of 3βHSD.