3β-HSD in songbird brain: subcellular localization and rapid regulation by estradiol.
The enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) catalyzes the conversion of dehydroepiandrosterone to androstenedione, thereby playing a key role in sex steroid synthesis. In peripheral tissues, 3β-HSD is membrane-bound, is present in both mitochondria and microsomes, and is regulated differentially in these two subcellular compartments. In the brain, 3β-HSD is present, but its subcellular compartmentalization is unknown. Here, in Study 1, we examined the subcellular localization of 3β-HSD in the brain of a songbird, the zebra finch. In Study 2, in males and females, we determined whether 3β-HSD activity in different subcellular compartments is rapidly regulated by in vitro treatment with estradiol (E(2) ), which has many rapid effects on the brain. Brain 3β-HSD was enriched primarily in microsomes and secondarily in mitochondria and synaptosomes. In both males and females, E(2) treatment rapidly (within 5 min) inhibited 3β-HSD activity in both mitochondria/synaptosomes and microsomes, with greater inhibition in microsomes. We also assessed the activity of 5β-reductase, which acts on androstenedione. E(2) rapidly inhibited 5β-reductase activity in microsomes only. This is the first study to examine the subcellular localization of 3β-HSD in the brain, and the data demonstrate the importance of subcellular localization for the regulation of steroidogenic enzymes in the brain.
Pradhan
Devaleena S
DS
Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
Lau
Loretta Y M
LY
Schmidt
Kim L
KL
Soma
Kiran K
KK
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D001923:Brain Chemistry / Q000502:physiology; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D046369:Finches / Q000502:physiology*; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D012727:Sex Characteristics; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism
D003687:Dehydroepiandrosterone; D004958:Estradiol; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase