**5. Genetic markers**

428 Endometriosis - Basic Concepts and Current Research Trends

Aromatase P450 is the key enzyme for biosynthesis of oestrogen, which is an essential hormone for the establishment and growth of endometriosis. There is no detectable aromatase enzyme activity in normal endometrium; therefore, oestrogen is not locally produced in endometrium. Endometriosis tissue, however, contains very high levels of aromatase enzyme, which leads to production of significant quantities of oestrogen (Dheenadayalu et al., 2002). Moreover, one of the best-known mediators of inflammation and pain, prostaglandin E2 (PGE2), was found to be the most potent known inducer of aromatase activity in endometriotic stromal cells. The clinical significance of local aromatase activity that is induced strikingly by PGE2 in endometriotic tissue was exemplified recently by the successful use of an aromatase inhibitor to treat an unusually aggressive case of recurrent postmenopausal endometriosis that was resistant to any other surgical or hormonal modalities of treatment. Therefore, the aberrant expression of aromatase P450 in endometriotic tissue, in contrast to eutopic endometrium, justifies the local biosynthesis of estrogen that promotes the growth of these lesions and possibly mediates the resistance to conventional hormonal treatments, which is observed in a number of women with endometriosis. The molecular mechanisms that are responsible for aberrant aromatase P450 expression may provide insights into the etiology of endometriosis and lead to identification of molecular targets for the development of novel treatment strategies. Although endometrial aromatase P450 expression does not correlate with the disease stage, a recent study demonstrated that detection of aromatase P450 transcripts in the endometrium of

endometriosis patients might be a potential qualitative marker of endometriosis.

expression suggested a difference in hormonal regulation between the two sites.

The expression of receptors for the ovarian steroid hormones oestrogen and progesterone was studied immunohisto-chemically using monoclonal antibodies. The quantification of these receptors in the endometrium could be potentially useful in screening for this disease. The eutopic endometrium of patients with endometriosis is different from endometrium of fertile controls regarding apoptosis, cytokines and other characteristics. Although cyclic changes were also detected in ectopic endometrium, different patterns of receptor

The concentrations of steroid receptors in ectopic endometrium increased gradually as the cycle progressed. Compared with eutopic endometrium, oestrogen and progesterone receptor concentrations were significantly lower in the proliferative phase, similar in the early secretory phase and significantly higher in the late secretory phase. The different patterns of receptor expression suggested different hormonal regulations between eutopic

There are two isoforms for oestrogen (ER) and progesterone (PR) receptors-ER-α and ER-β, PRA and PR-B. These isoforms exist in the endometrium and their function and content are different from one another. The different concentrations and biological activity of steroid receptor isoforms might lead to various hormonal responsiveness of ectopic endometrium. High concentrations of ER and PR in the ectopic endometrium during the secretory phase

**4. Endometrial tissue biochemical markers** 

**4.1 Aromatase P450** 

**4.2 Hormone receptors** 

and ectopic endometrium.

Several genetic abnormalities or mutations have been suggested that might be related to endometriosis. Many technological approaches can help identify possible genetic markers of endometriosis. A number of technologies have emerged to facilitate progress in this direction (Taylor et al., 2002). Gene based technologies includes subtractive cDNA hybridization and cDNA microarray techniques.
