title: 3 beta-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.
authors.affiliation: Department of Obstetrics and Gynecology, Cecil H. and Ida Green Center for Reproductive Sciences, University of Texas, Southwestern Medical Center, Dallas 75235.
authors.forename: K M
authors.initials: KM
authors.lastname: Doody
authors.forename: B R
authors.initials: BR
authors.lastname: Carr
authors.forename: W E
authors.initials: WE
authors.lastname: Rainey
authors.forename: W
authors.initials: W
authors.lastname: Byrd
authors.forename: B A
authors.initials: BA
authors.lastname: Murry
authors.forename: R C
authors.initials: RC
authors.lastname: Strickler
authors.forename: J L
authors.initials: JL
authors.lastname: Thomas
authors.forename: J I
authors.initials: JI
authors.lastname: Mason
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis*; D000311:Adrenal Glands / Q000196:embryology* / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis / Q000378:metabolism; D015151:Immunoblotting; D007535:Isomerases / Q000032:analysis*; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000032:analysis* / Q000096:biosynthesis; D011375:Progesterone Reductase / Q000032:analysis* / Q000096:biosynthesis; D013251:Steroid Isomerases / Q000032:analysis* / Q000096:biosynthesis; D014018:Tissue Distribution
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D009097:Multienzyme Complexes; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D011375:Progesterone Reductase; D007535:Isomerases; D013251:Steroid Isomerases; D006854:Hydrocortisone