Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

Abstract

Androgen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated transsexual female patients. This was compared with AR expression in the ovaries and uteri of premenopausal and postmenopausal women not receiving treatment and in 10 ovaries of female patients with polycystic ovarian disease (PCOD). In the normal ovaries germinal epithelium, granulosa cells of antral follicles, corpus luteum, and thecal and stromal cells exhibited moderate AR expression. The more intense and uniform staining of ovarian stroma of female transsexual patients and those of patients with PCOD compared with ovarian stroma of normal controls was most remarkable. This similarity in histology and distribution of ARs supports the hypothesis that PCOD is an androgen-mediated disorder. Immunostaining for ARs was only occasionally detectable in the uteri of premenopausal and postmenopausal women. In contrast, myometrial and endometrial stroma of the uteri of female transsexual patients displayed an intense and diffuse nuclear immunostaining, but glandular epithelia remained unstained. Western blot analysis of the ovaries and uterine myometrial tissue samples from transsexual female patients confirmed the presence of the 110-kd AR molecule. Because the androgen treatment of some transsexual female patients was discontinued 6 weeks before they underwent hysterosalpingo-oophorectomy, our data indicate a stable and persistent androgen-induced up-regulation of AR expression in ovaries.

Mechanisms for c-myc Induced Mouse Mammary Gland Carcinogenesis and for the Synergistic Role of TGF(alpha) in the Process

“…Since ovarian cysts have a higher risk to progress into ovarian cancer [243][244][245], elevated androgens may be interrelated to the ovarian cancer development [246][247][248]. This hypothesis is supported by the facts that AR is expressed in normal ovaries and in most ovarian cancer biopsies [249][250][251][252]. Because elevated estrogens have been associated with an increased risk of ovarian cancer [246;247;253], it cannot be excluded that increased estrogen and androgens may actually play a combined role.…”

Role of androgens in normal and pathological ovarian function

“…There the intensity of AR expression increased from the mural granulosa cells to the cumulus cells, and this gradient became more pronounced as antral follicles developed to the preovulatory developmental stage (Lenie & Smitz 2009 (Hild-Petito et al 1991, Hillier et al 1997 and mRNA are expressed in mural granulosa cells and theca cells of primate antral and periovulatory follicles; however, the expression weakens in the granulosa cells as they progress from less mature follicles to periovulatory follicles (Hillier et al 1997). AR immunostaining is also present in human granulosa and theca cells of antral and preovulatory follicles (Suzuki et al 1994, Chadha et al 1994, and AR mRNA and protein are detectable in granulosa cells extracted from human small and large antral follicles (Catteau-Jonard et al 2008, Nielsen et al 2011.…”

Androgen actions in the ovary: balance is key

“…Studies across species reported that ARs are expressed in theca cells, granulosa cells (GCs), and the oocyte of the follicle and throughout most stages of follicular development (Horie et al 1992, Chadha et al 1994, Hirai et al 1994, Suzuki et al 1994, Tetsuka & Hillier 1996, Szoltys & Slomczynska 2000, Slomczynska & Tabarowski 2001, Gill et al 2004, Hampton et al 2004, Juengel et al 2006. However, their expression patterns may differ between ovarian cell types (Tetsuka & Hillier 1996, Szoltys & Slomczynska 2000 and in most species, AR is abundant in the preantral/antral stages of follicular development but declines as follicles mature to the preovulatory stage (Horie et al 1992, Chadha et al 1994, Suzuki et al 1994, Duffy et al 1999, Hampton et al 2004, Juengel et al 2006. In fact, AR is expressed in cell-specific regions of human ovarian follicles at all stages of follicular development beyond the primordial phase (Rice et al 2007).…”