Conclusions We identified a novel duplication at 15q21.2 in AEXS, and found that aromatase inhibitor (AI) plus GH might provide a better growth-promoting approach for AEXS patients.
CYP19A1 amplification caused increased aromatase activity and estrogen-independent ERα binding to target genes, resulting in CYP19A1<sup>amp</sup> cells showing decreased sensitivity to AI treatment.
Recently, several germline rearrangements at 15q21 have been shown to cause overexpression of the aromatase gene CYP19A1 and resulting aromatase excess syndrome.
Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon).
Aromatase excess syndrome: identification of cryptic duplications and deletions leading to gain of function of CYP19A1 and assessment of phenotypic determinants.
Aromatase excess syndrome: identification of cryptic duplications and deletions leading to gain of function of CYP19A1 and assessment of phenotypic determinants.
Taken together, these results suggest that PGE(2) via EP(2) and EP(4) activates the cAMP-->PKA-->CREB pathway leading to enhanced CYP19 transcription and increased aromatase activity.
Aromatase inhibitors successfully treat breast cancer and endometriosis, whereas their roles in endometrial cancer, uterine fibroids, and aromatase excess syndrome are less clear.
In conclusion, a family with the aromatase excess syndrome is described, in which the condition was inherited in an autosomal dominant manner, led to feminizing manifestations in both sexes, and was associated with the aberrant utilization of a novel transcript of the P450arom gene.
Conclusions We identified a novel duplication at 15q21.2 in AEXS, and found that aromatase inhibitor (AI) plus GH might provide a better growth-promoting approach for AEXS patients.
CYP19A1 amplification caused increased aromatase activity and estrogen-independent ERα binding to target genes, resulting in CYP19A1<sup>amp</sup> cells showing decreased sensitivity to AI treatment.
These results indicate that AEXS is caused by duplications involving CYP19A1 and simple and complex rearrangements that presumably lead to the usage of cryptic promoters of several neighboring genes.
Taken together, these results suggest that PGE(2) via EP(2) and EP(4) activates the cAMP-->PKA-->CREB pathway leading to enhanced CYP19 transcription and increased aromatase activity.
Potentially the elevated IGF-I and adrenal androgen levels, increased aromatase activity and increased 'free' sex steroid levels consequent to lower SHBG levels could all promote activity of the GnRH pulse generator.
Potentially the elevated IGF-I and adrenal androgen levels, increased aromatase activity and increased 'free' sex steroid levels consequent to lower SHBG levels could all promote activity of the GnRH pulse generator.