Neurotransmitter-mediated regulation of brain aromatase: protein kinase C- and G-dependent induction.
Aromatase in the diencephalic neurons, the level of which increases transiently during the prenatal to neonatal period, has been suggested to be involved in control of sexual behavior and differentiation of the CNS. Effects of neurotransmitters on levels of aromatase mRNA in cultured neurons were investigated to determine factors regulating the developmental increase that occurs in level of fetal brain aromatase. The expression of aromatase in diencephalic neurons of fetal mice at embryonic day 13, cultured in vitro, was significantly affected by alpha 1-adrenergic receptor ligands. Aromatase mRNA levels were higher in neurons treated with the alpha 1-agonist phenylephrine than in control neurons, whereas prazosin, an alpha 1-antagonist, suppressed this increase, and ligands for alpha 2- or beta-adrenergic receptors did not exert any influence. The profile of alpha 1-adrenergic receptor subtypes during actual development in vivo suggested that the alpha 1B subtype is in fact responsible for the signal transduction. Substance P, cholecystokinin, neurotensin, and brain natriuretic peptide also increased the level of expression along with phorbol 12-myristate 13-acetate and dibutyrylcyclic GMP, whereas forskolin and dibutyryl-cyclic AMP caused a decrease. These data indicate that stimulation via alpha 1 (possibly alpha 1B)-adrenergic receptors, as well as receptors of specific neuropeptides, controls the expression of aromatase in embryonic day 13 diencephalic neurons through activation of protein kinase C or G. beta-Adrenergic receptors would not appear to participate in the regulation, judging from their developmental profile, although cyclic AMP might be a suppressive second messenger.
Abe-Dohmae
S
S
Department of Biochemistry, Nagoya City University Medical School, Japan.
Takagi
Y
Y
Harada
N
N
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis*; D001921:Brain / Q000201:enzymology*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology; D004027:Diencephalon / Q000201:enzymology*; D005314:Embryonic and Fetal Development; D004790:Enzyme Induction; D005260:Female; D005333:Fetus; D019204:GTP-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D051379:Mice; D008813:Mice, Inbred ICR; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D016900:Neurofilament Proteins / Q000096:biosynthesis; D009474:Neurons / Q000201:enzymology*; D009479:Neuropeptides / Q000494:pharmacology*; D009496:Neurotensin / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; C044882:neurofilament protein L; D020097:Natriuretic Peptide, Brain; D010656:Phenylephrine; D013373:Substance P; D009496:Neurotensin; D003994:Bucladesine; D002766:Cholecystokinin; D001141:Aromatase; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D011224:Prazosin