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Immunohistochemical localization and biological activity of the steroidogenic enzyme cytochrome P450 17α‐hydroxylase/C17, 20‐lyase (P450 C17 ) in the frog brain and pituitary
Author(s) -
Do Rego Jean Luc,
Tremblay Yves,
LuuThe Van,
Repetto Emanuela,
Castel Hélène,
Vallarino Mauro,
Bélanger Alain,
Pelletier Georges,
Vaudry Hubert
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04209.x
Subject(s) - pregnenolone , medicine , endocrinology , dehydroepiandrosterone , diencephalon , biology , cerebrum , pars intermedia , pituitary gland , hormone , hypothalamus , central nervous system , steroid , androgen
It is now clearly established that the brain has the capability of synthesizing various biologically active steroids including 17‐hydroxypregnenolone (17OH‐Δ 5 P), 17‐hydroxyprogesterone (17OH‐P), dehydroepiandrosterone (DHEA) and androstenedione (Δ 4 ). However, the presence, distribution and activity of cytochrome P450 17α‐hydroxylase/C17, 20‐lyase (P450 C17 ), a key enzyme required for the conversion of pregnenolone (Δ 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 3β‐hydroxysteroid dehydrogenase‐like immunoreactivity. Incubation of telencephalon, diencephalon, mesencephalon, metencephalon or pituitary explants with [ 3 H]Δ 5 P resulted in the formation of several tritiated steroids including 17OH‐Δ 5 P, 17OH‐P, DHEA and Δ 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.