Endometriosis is an
estrogen-dependent disease of women of reproductive age. Recent studies demonstrate that
endometriosis per se express high levels of
estrogen synthetase (
aromatase P450). The resulting
estrogen synthesized in situ may play a role in the development and exacerbation of the disease. For ovarian
endometrioma, previous studies have been conducted ex vivo using cells obtained from
endometrioma and have demonstrated that steroidogenic factor-1 is involved in the expression of
aromatase. The aim of the present study was to provide in vivo evidence that steroidogenic factor-1 plays an important role in the regulation and overexpression of
aromatase P450 in situ. First, promoter use of
aromatase P450 in
endometrioma tissue was determined using quantitative methods. Ovarian
endometrioma tissue was chopped into small pieces, and two exon 1-specific transcripts of
aromatase P450 (PII-specific and I.4-specific transcripts) were quantified using competitive RT-PCR. PII-specific transcript was more abundant than the I.4-specific transcript in 13 of the 15
endometriomas and less abundant in the remaining two. Spatial distribution of
aromatase P450 transcripts in these
endometrioma tissues revealed heterogeneous expression in the
cyst wall, demonstrating wide variability even in the same
endometrioma. Two possible regulators of
aromatase expression (
steroidogenic factor-1 and IL-1 beta) were then measured in all
endometrioma samples and the correlation between
aromatase P450 transcripts and these possible regulators in the
endometrioma samples were tested using Spearman's rank order correlation test. Levels of steroidogenic factor-1 transcript were found to correlate closely with levels of PII-specific transcript in eight of nine
endometriomas examined. On the other hand, the level of
IL-1 beta weakly correlated with I.4-specific transcripts in three of the nine
endometriomas. We next histologically examined samples of four
endometriomas in which complete sets of tissue samples corresponded to the
RNA samples. We could not identify any specific pathology to explain the heterogeneous expression of PII-specific transcripts of
aromatase P450, although the number of CD-68 positive macrophages in the tissue sections weakly correlated with the level of I.4-specific transcript in two of four
endometriomas. These results provide strong evidence that promoter II is the predominant promoter of
aromatase P450 in
endometrioma tissues in vivo and that steroidogenic factor-1 in situ is a major determinant of
aromatase P450 overexpression in
endometrioma tissues in vivo.