Immunohistochemical localization and biological activity of the steroidogenic enzyme cytochrome P450 17α-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-Δ5P), 17-hydroxyprogesterone (17OH-P), dehydroepiandrosterone (DHEA) and androstenedione (Δ4). However, the presence, distribution and activity of cytochrome P450 17α-hydroxylase/C17, 20-lyase (P450C17), a key enzyme required for the conversion of pregnenolone (Δ5P) and progesterone (P) into these steroids, are poorly documented. Here, we show that P450C17-like immunoreactivity is widely distributed in the frog brain and pituitary. Prominent populations of P450C17-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, P450C17-like immunoreactivity was almost exclusively located in neurons. In several hypothalamic nuclei, P450C17-positive cell bodies also contained 3β-hydroxysteroid dehydrogenase-like immunoreactivity. Incubation of telencephalon, diencephalon, mesencephalon, metencephalon or pituitary explants with [3H]Δ5P resulted in the formation of several tritiated steroids including 17OH-Δ5P, 17OH-P, DHEA and Δ4. De novo synthesis of C21 17-hydroxysteroids and C19 ketosteroids was reduced in a concentration-dependent manner by ketoconazole, a P450C17 inhibitor. This is the first detailed immunohistochemical mapping of P450C17 in the brain and pituitary of any vertebrate. Altogether, the present data provide evidence that CNS neurons and pituitary cells can synthesize androgens.