title: Adrenal 20alpha-hydroxysteroid dehydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone.
abstract: The enzyme 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) is a progesterone-catabolizing enzyme that is highly expressed in mouse ovaries and adrenals. Although the functional significance of ovarian 20alpha-HSD for the induction of parturition has been defined, regulation and distribution of 20alpha-HSD in the adrenal gland has not been determined. We demonstrate that the expression of adrenal 20alpha-HSD is restricted to the X-zone, a transient zone between the adrenal cortex and the medulla of yet unknown function. Adrenal 20alpha-HSD activity in male mice peaks at 3 wk of age and disappears thereafter, whereas 20alpha-HSD enzyme activity is maintained in adrenals from nulliparous female animals. Testosterone treatment of female mice induces rapid involution of the X-zone that is associated with the disappearance of the 20alpha-HSD-positive cells. Conversely, reappearance of 20alpha-HSD expression and activity in male animals is evident after gonadectomy. Moreover, pregnancy, but not pseudopregnancy, is accompanied by X-zone regression and loss of 20alpha-HSD activity. Pregnancy-induced X-zone regression and -abolished 20alpha-HSD expression is partially restored in animals that were kept from nursing their pups. We found that in addition to its progesterone-reducing activity, 20alpha-HSD also functions as an 11-deoxycorticosterone-catabolizing enzyme. The unaltered growth kinetics of the X-zone in 20alpha-HSD knockout animals suggests that 20alpha-HSD is not required for the regulation of X-zone growth. However, 20alpha-HSD expression and enzymatic activity in all experimental paradigms is closely correlated with the presence of the X-zone. These findings provide the basis for 20alpha-HSD as a reliable marker of the murine X-zone.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Hershkovitz
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
authors.forename: Steffen
authors.initials: S
authors.lastname: Klammer
authors.forename: Margalit
authors.initials: M
authors.lastname: Krup
authors.forename: Yacob
authors.initials: Y
authors.lastname: Weinstein
mesh_terms: D043607:20-alpha-Hydroxysteroid Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D000833:Animals, Suckling; D003900:Desoxycorticosterone / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007774:Lactation / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009928:Organ Specificity; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D011555:Pseudopregnancy / Q000201:enzymology; D015385:Zona Reticularis / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development
chemical_list: D000728:Androgens; D003900:Desoxycorticosterone; D011374:Progesterone; D003907:Dexamethasone; D043607:20-alpha-Hydroxysteroid Dehydrogenase