Synergism between androgens and estrogens in the induction of aromatase and its messenger RNA in the brain.
It is established that testosterone (T) increases aromatase activity (AA) in the quail brain and that this induction of AA represents a limiting factor in the activation of male copulatory behavior. This action of T presumably results from an induction of aromatase synthesis since the number of aromatase-immunoreactive (ARO-ir) cells increases and, in parallel, there is an increase in aromatase mRNA as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) technology. The specific role of androgenic and estrogenic metabolites of T in this induction is not yet clear but product-formation assays suggest that both types of compounds synergize to increase AA. The exact role of androgens and estrogens in the induction of aromatase was examined by studying both the aromatase protein by immunocytochemistry and the aromatase mRNA by RT-PCR in castrated quail that had been treated with T or its androgenic metabolite, 5 alpha-dihydrotestosterone (DHT) or its estrogenic metabolite, estradiol-17 beta (E2) or both DHT and E2 simultaneously. A specific quantitative PCR technique using a modified aromatase as internal standard was developed for this purpose. T increased the number of ARO-ir cells in all brain areas and increased the concentration of ARO mRNA in the preoptic area-anterior hypothalamus (POA-aHYP) and in the posterior hypothalamus (pHYP). E2-treated birds had more ARO-ir cells than castrates in the posterior part of the medial preoptic nucleus (POM), in the bed nucleus stria terminalis (BNST) and tuber. Their aromatase mRNA concentration was significantly increased in the POA-aHYP but this effect did not reach significance in the pHYP. DHT by itself had no effect on either the number of ARO-ir cells (all brain regions considered) or the concentration of aromatase mRNA. DHT, however, synergized with E2, both in inducing ARO-ir neurons and in increasing aromatase mRNA concentration. This synergism was shown to be statistically significant in several brain areas. These data demonstrate that both androgens and estrogens regulate aromatase at the pretranslational level. Because the percentage increase in the number of ARO-iR cells was in general very similar to the increase in aromatase mRNA concentration, these data also suggest that these steroids regulate aromatase mostly by changing its mRNA synthesis or catabolism.
Harada
N
N
Division of Molecular Genetics, Fujita Health University, Toyoake, Japan.
Abe-Dohmae
S
S
Loeffen
R
R
Foidart
A
A
Balthazart
J
J
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003370:Coturnix; D004357:Drug Synergism; D004790:Enzyme Induction; D004967:Estrogens / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects*; D013739:Testosterone / Q000378:metabolism*
D000728:Androgens; D004967:Estrogens; D012333:RNA, Messenger; D013739:Testosterone; D001141:Aromatase