Anogenital distance (AGD) plasticity in adulthood: Implications for its use as a biomarker of fetal androgen action

Rod T Mitchell, Will Mungall, Chris McKinnell, Richard M Sharpe, Lyndsey Cruickshanks, Laura Milne, Lee B Smith

Research output: Contribution to journalArticlepeer-review

Abstract

Androgen action during the fetal masculinization-programming window (MPW) determines the maximum potential for growth of androgen-dependent organs (e.g. seminal vesicles, prostate, penis, perineum) and is reflected in anogenital distance (AGD). As such, determining AGD in postnatal life has potential as a lifelong easily accessible biomarker of overall androgen action during the MPW. However, whether the perineum remains androgen-responsive in adulthood and thus responds plastically to perturbed androgen drive remains unexplored. To determine this, we treated adult male rats with either the anti-androgen Flutamide, or the estrogen Diethylstilbestrol (DES) for five weeks, followed by a four-week wash-out period of no treatment. We determined AGD, and its correlate anogenital index (AGI; AGD relative to bodyweight), at weekly intervals across this period and compared this to normal adult rats (male and female), castrated male rats, and appropriate vehicle controls. These data showed that, in addition to reducing circulating testosterone and seminal vesicle weight, castration significantly reduced AGD (by ∼17), demonstrating that there is a degree of plasticity in AGD in adulthood. Flutamide treatment increased circulating testosterone yet also reduced seminal vesicle weight due to local antagonism of androgen receptor. Despite this suppression, surprisingly, Flutamide treatment had no effect on AGD at any time-point. In contrast, whilst DES treatment suppressed circulating testosterone and reduced seminal vesicle weight, it also induced a significant reduction in AGD (by ∼11%), which returned to normal one week after cessation of DES treatment. We conclude that AGD in adult rats exhibits a degree of plasticity, which may be mediated by modulating local androgen/estrogen action. The implications of these findings regarding the use of AGD as a life-long clinical biomarker of fetal androgen action are discussed.

Original languageEnglish
Pages (from-to)en20141534
JournalEndocrinology
Early online date6 Nov 2014
DOIs
Publication statusPublished - 1 Jan 2015

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