Immunohistochemical localization and biological activity of the steroidogenic enzyme cytochrome P450 17alpha-hydroxylase/C17, 20-lyase (P450C17) in the frog brain and pituitary.
It is now clearly established that the brain has the capability of synthesizing various biologically active steroids including 17-hydroxypregnenolone (17OH-Delta(5)P), 17-hydroxyprogesterone (17OH-P), dehydroepiandrosterone (DHEA) and androstenedione (Delta(4)). However, the presence, distribution and activity of cytochrome P450 17alpha-hydroxylase/C17, 20-lyase (P450(C17)), a key enzyme required for the conversion of pregnenolone (Delta(5)P) and progesterone (P) into these steroids, are poorly documented. Here, we show that P450(C17)-like immunoreactivity is widely distributed in the frog brain and pituitary. Prominent populations of P450(C17)-containing cells were observed in a number nuclei of the telencephalon, diencephalon, mesencephalon and metencephalon, as well as in the pars distalis and pars intermedia of the pituitary. In the brain, P450(C17)-like immunoreactivity was almost exclusively located in neurons. In several hypothalamic nuclei, P450(C17)-positive cell bodies also contained 3beta-hydroxysteroid dehydrogenase-like immunoreactivity. Incubation of telencephalon, diencephalon, mesencephalon, metencephalon or pituitary explants with [(3)H]Delta(5)P resulted in the formation of several tritiated steroids including 17OH-Delta(5)P, 17OH-P, DHEA and Delta(4). De novo synthesis of C(21) 17-hydroxysteroids and C(19) ketosteroids was reduced in a concentration-dependent manner by ketoconazole, a P450(C17) inhibitor. This is the first detailed immunohistochemical mapping of P450(C17) in the brain and pituitary of any vertebrate. Altogether, the present data provide evidence that CNS neurons and pituitary cells can synthesize androgens.
Do Rego
Jean Luc
JL
INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP 23), University of Rouen, Mont-Saint-Aignan, France.
Tremblay
Yves
Y
Luu-The
Van
V
Repetto
Emanuela
E
Castel
Hélène
H
Vallarino
Mauro
M
Bélanger
Alain
A
Pelletier
Georges
G
Vaudry
Hubert
H
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000201:enzymology*; D002452:Cell Count; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010902:Pituitary Gland / Q000201:enzymology*; D011893:Rana esculenta; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D014018:Tissue Distribution
D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D010751:Phosphopyruvate Hydratase