Estrogen and androgen receptor expression in surface epithelium and inclusion cyst in the ovary of premenopausal and postmenopausal women

Abstract

BackgroundThe importance of surface epithelium and epithelial inclusion cysts in the ovary arises from studies demonstrating that these structures are susceptible to epithelial ovarian cancer development. The expression of estrogen receptor alpha (ER alpha), androgen receptor (AR), in epithelial cells of the ovary from premenopausal and postmenopausal women is interesting because sexual steroid hormones are involved in cell growth and differentiation.MethodsThe presence of ER alpha, AR, and the orphan G protein-coupled receptor 30 (GPR30) was demonstrated by immunofluorescence in ovaries obtained from 79 pre and postmenopausal patients, undergoing histero-salpingo-oophorectomy for proliferative gynecological diseases. The proportion of patients that displayed positive reaction for estrogen and androgen receptors in epithelial cells of the ovary was evaluated according to menopausal status and associated pathology.ResultsThe proportion of patients that displayed a positive receptor expression in the epithelial cells of the ovarian surface and cortical inclusion cysts shows that ER alpha is present in 20 of 79 patients (0.25), AR in 33 of 79 (0.42) and GPR30 in 38 of 55 (0.69). There are no differences in ER alpha, AR, and GPR30 expression between pre and postmenopausal patients and considering the associated pathology, proportions for ER alpha and GPR30 are similar. The patients with cervical cancer show a higher proportion of AR expression in epithelial cells of the ovary, which is statistically significant (P < 0.01) compared with patients with other proliferative diseases.ConclusionsThe presence of ER alpha, AR, and GPR30 in the surface epithelial ovarian cells and its derivatives are observed with a proportion that is specific for each receptor. The proportion of expression for these receptors in the epithelial cells of the ovary does not change after menopause. The proportion of ovaries with AR positive epithelial cells in patients with cervical squamous carcinoma is higher compared with other gynecological pathologies.

Evidence of androgen action in endometrial and ovarian cancers

“…A mouse model using a conditional double KO of Dicer (Dicer1) and Pten demonstrated that high-grade serous cancers develop in the fallopian tube and metastasise to the ovary (Kim et al 2012). Although there is still evidence to support OSE cells as the originating cell type for some ovarian cancers (Auersperg 2013), the fact that both OSE cells and cells within the fallopian tube epithelium express AR (Edmondson et al 2002, Horne et al 2009, Mendez et al 2013 highlights the potential for androgens to modulate disease development and progression. Stem-like epithelial cells from the distal end of the fallopian tube capable of clonal growth and self-renewal have also been identified which may play a role in the initiation of serous tumours, although the impact of androgens on this cell population has not been investigated (Paik et al 2012).…”

New Insights into Estrogen Signaling

“…Notably the multiple ovarian cysts and elevated serum testosterone suggest that the woman is a polycystic ovary syndrome (PCOS) patient, the cause and mechanism of the disease is currently unknown. In addition to the mildly elevated levels of gonadotropins, probably the dramatically high levels (10 times) of estrogens and other ER or receptor-like partners cannot be excluded, since ERβ and newly identified 3rd estrogen receptor, the membrane G protein coupled receptor (GPR30) are expressed in the ovaries [18][19][20]. This consideration is an agreement of the animal study that demonstrated both elevated LH and ERβ are required for the formation of ovarian cysts [21].…”

Molecular Regulation of Androgen Receptors in Major Female Reproductive System Cancers

“…These co-regulators including coactivators and corepressors modulate AR activity and activate ARE-mediated transcription in ovarian cancer cells, although most of them also interact with other receptors [ 59 ]. OVCA is more common in perimenopause and post-menopause, when the balance of steroids in the ovary favors A. Paradoxically, the expression ratio of AR in ovarian epithelial cells does not change after menopause [ 60 ]. It is speculated that the A may act through non-receptor binding pathways.…”