The effects of androgens on steroidogenesis in the ovary of Atlantic croaker (Micropogonias undulatus) : mechanism of action, the biochemical characterization of a membrane androgen receptor, and the chronic effects of exposure to an environmental antiandrogen
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This study focuses on the actions of androgens in the gonads of the Atlantic croaker (Micropogonias undulatus). Physiologically relevant concentrations of androgens are shown to inhibit in vitro ovarian production of estradiol through a rapid, nongenomic mechanism initiated at the cell surface, which is not reversed by co-incubation with antiandrogens. Experiments with steroid precursors suggest that the site of androgen action is distal to 17OH-progesterone in the steroidogenic pathway. Further investigation revealed the presence of a membrane androgen receptor (mAR) in the croaker ovary that may mediate this androgen action. This mAR demonstrates a high affinity and finite capacity for androgen binding, which vii is both tissue and steroid specific. The croaker ovarian mAR is relatively unique among androgen receptors, since it binds dihydrotestosterone, testosterone, and progesterone with high affinity. No other C21 or any C18 steroid tested binds with high affinity. Androgen association and dissociation from the mAR is rapid. Levels of mAR are highest in reproductively mature gonads, which suggests a role for this receptor in female reproduction. Finally, the effects of chronic in vivo exposure to p,p’-DDE or cyproterone acetate (CA), which have been shown to act as antiandrogens in mammals, on indicators of reproductive health in croaker are described. Although the results were not consistent at all doses and time points of sampling, exposure to p,p’-DDE in vivo significantly inhibited gonadal growth, circulating sex steroid levels, and in vitro gonadal steroidogenesis in both males and females. The effects were subtle and mostly observed in fish treated with the highest dose of p,p’-DDE (0.05 mg/100 g bw/day) for the longest time period (24 weeks). Effects of the antiandrogenCA on gonadal function differed from those of p,p’-DDE, so it is unclear whether the observed effects of p,p’-DDE were antiandrogenic. The finding that p,p’-DDE can affect gonadal growth and disrupt the reproductive endocrine system in female and male croaker suggests that this chemical could impair reproduction in fish and other wildlife species in severely contaminated sites.