Progesterone 5-alpha-reduction in neuronal and in different types of glial cell cultures: type 1 and 2 astrocytes and oligodendrocytes.
Progesterone, like testosterone, can be converted in the brain into 5-alpha-reduced metabolites (5-alpha-pregnan-3,20-dione, DHP; 5-alpha-pregnan-3-alpha-ol-20-one, THP). Recently we have shown that testosterone is 5-alpha-reduced to DHT mainly in neurons, while glial cells possess this enzymatic activity only in limited amounts. On the other hand, a glial cell type (type 1 astrocytes) is almost exclusively responsible for the further metabolism of DHT into 3-alpha-diol. The aim of the present studies was that of evaluating the formation of the 5-alpha-reduced metabolites of progesterone in cultures of neurons, type 1 and 2 astrocytes and oligodendrocytes. The data here presented indicate that, similarly to what happens when testosterone is used as the substrate, the 5-alpha-reductase which metabolizes progesterone shows a significantly higher activity in neurons than in glial cells; however, also type-1 and type-2 astrocytes as well as oligodendrocytes possess some ability to 5-alpha-reduce progesterone. On the contrary, the 3-alpha-hydroxysteroid dehydrogenase (3-alpha-HSD), the enzyme which converts DHP into THP, appears to be mainly present in type-1 astrocytes; much lower levels of this enzyme are present in neurons and in type-2 astrocytes. At variance with the previous results obtained utilizing androgens as precursors, oligodendrocytes show a considerable 3-alpha-HSD activity, even if this is statistically lower than that present in type-1 astrocytes. The existence of isoforms of the enzymes involved in androgen and progesterone metabolism may explain these data.
Melcangi
R C
RC
Department of Endocrinology, University of Milano, Italy.
Celotti
F
F
Martini
L
L
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism*; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000378:metabolism; D007150:Immunohistochemistry; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D009836:Oligodendroglia / Q000201:enzymology / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D011280:Pregnanolone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D013196:Dihydrotestosterone; D011280:Pregnanolone; D010088:Oxidoreductases; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C022447:3-oxo-5-alpha-steroid 4-dehydrogenase (NADP(+))