Changes in distribution of androgen receptor during maturation of rat ovarian follicles

Abstract

Sequential changes in androgen receptor (AR) distribution were investigated in rat ovarian follicles during their physiological development. Mature female Wistar rats, exhibiting a regular 4-day oestrous cycle, were killed in succession on the day of oestrus, metoestrus, dioestrus, and pro-oestrus. Excised ovaries were submitted to immunohistochemical procedure in which polyclonal androgen receptor antibody, avidin-biotin-peroxidase complex, and DAB were used. Strong AR immunostaining was located predominantly in the nuclei of the granulosa layer of preantral and very early antral follicles, present in the ovaries at all stages of the oestrous cycle. At early oestrus a decline in AR was noted in the mural granulosa cells of presumably recruited early antral follicles. The decline involved the area of appearing pseudostratification. During metoestrus and dioestrus AR decline proceeded towards the antrum, but the antral regions connected with COC by strings of granulosa cells or lying in close proximity to COC were always strongly AR-positive. It was only on the day of pro-oestrus that AR was confined to COCs and a few antral cells bordering the antrum. These findings indicate that during the oestrous cycle AR decline starts in the mural granulosa cells of oestrous antral follicles beginning to differentiate and is completed at pro-oestrus, but even before ovulation it does not extend to COC. The persistence of AR immunostaining in the latter region suggests that androgens can play here a paracrine role especially before ovulation. Atretic follicles showed a different pattern of AR distribution, dependent on their stage of development and the advancement of this process.

Role of androgens in normal and pathological ovarian function

“…During rat antral follicular growth, AR expression progressively declines in the outer mural granulosa cells of later-stage antral follicles, but the cumulus cells surrounding the oocyte maintain strong AR-positive staining (Szoltys & Slomczynska 2000). This gradient of AR expression intensity was also confirmed in mouse antral follicles collected from an in vitro culture system.…”

“…Strong AR immunostaining is observed in granulosa cells of early rat antral follicles (Szoltys & Slomczynska 2000). During rat antral follicular growth, AR expression progressively declines in the outer mural granulosa cells of later-stage antral follicles, but the cumulus cells surrounding the oocyte maintain strong AR-positive staining (Szoltys & Slomczynska 2000).…”

“…AR expression has not been detected in primordial follicles of rat (protein: Szoltys & Slomczynska 2000), bovine (mRNA: Hampton et al 2004), ovine (mRNA: Juengel et al 2006), primate (protein: Hild-Petito et al 1991 or human (mRNA: Rice et al 2007;protein: Suzuki et al 1994, Horie et al 1992 …”

“…AR immunostaining is observed in the oocyte, granulosa cells and theca cells of rat preantral follicles (Szoltys & Slomczynska 2000, Lenie & Smitz 2009 Weil et al 1998;protein: Hillier et al 1997). AR mRNA is also detectable in human preantral follicles (Rice et al 2007).…”

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).…”