Autonomous expression of aromatase during development of mouse brain is modulated by neurotransmitters.
A transient increase in aromatase activity is known to occur in the hypothalamus of rodents in pre- and postnatal periods. The mechanisms regulating such a developmental increase of brain aromatase was studied in fetal mouse diencephalic cells, by measuring aromatase mRNA levels by a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. When slices of diencephalon were cultured on embryonic day (E) 12, E13 and E15, the level of aromatase mRNA continued to increase for the first 2 to 3 days. A time-dependent increase of mRNA was also shown for 3 days in E13 neuronal cells dissociated with papain and cultured in chemically defined medium. However, no significant increase was observed in E10 or E11 brain cells cultured by either method. Aromatase mRNA was detected in neither cerebral cortex neurons nor astrocytes. An alpha1-selective adrenergic agonist, phenylephrine, increased aromatase in the E13 diencephalic neurons in culture, whereas prazosin, an alpha1-antagonist, suppressed the mRNA level. Ligands for alpha2- or beta-adrenergic receptors did not alter the mRNA level. Substance P, cholecystokinin, neurotensin, and brain natriuretic peptide as well as phorbol 12-myristate 13-acetate and dibutyryl-cyclic GMP all increased the mRNA level. We concluded that: (a) the developmental increase of aromatase mRNA in diencephalic neurons is an autonomous event and is perhaps genetically regulated after E12; (b) aromatase mRNA is expressed in a cell type- and region-specific manner; and (c) protein kinases C and G activated via receptors of the specific neurotransmitters may be involved in modulation of the developmental expression of aromatase mRNA.
Abe-Dohmae
S
S
Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
Takagi
Y
Y
Harada
N
N
D000818:Animals; D001141:Aromatase / Q000096:biosynthesis*; D001921:Brain / Q000196:embryology* / Q000201:enzymology*; D005314:Embryonic and Fetal Development; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis
D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D001141:Aromatase