Article

Steroid receptors and mammalian penile development: An unexpected role for progesterone receptor?

Institute for the Study and Treatment of Hypospadias, Department of Urology, School of Medicine, University of California, San Francisco, 94143, USA.
The Journal of Urology (Impact Factor: 3.75). 09/2006; 176(2):728-33. DOI: 10.1016/j.juro.2006.03.078
Source: PubMed

ABSTRACT We investigated the role of steroid receptors in normal and abnormal genital tubercle development in males and females. We hypothesized that progesterone receptor expression might be involved in abnormal development in both sexes.
We examined the effects of medroxyprogesterone acetate on steroid receptor mRNA expression and assessed the involvement of androgen receptor in the action of medroxyprogesterone acetate on genital tubercle development using androgen receptor deficient (Tfm) mice.
Quantitative reverse transcriptase polymerase chain reaction and morphological results demonstrated a pattern of virilized females and feminized males in medroxyprogesterone acetate exposed embryos. Progesterone receptor was the only steroid receptor examined that did not differ between medroxyprogesterone acetate treated males and vehicle treated females. At the morphological level in utero exposure to medroxyprogesterone acetate from gestational days 12 to 17 feminized male genital tubercles, producing a more proximal urethral opening. Female fetuses exposed for the same period exhibited virilized genitalia, with a more distal urethral opening. We also exposed Tfm mice to medroxyprogesterone acetate to assess the role of androgen receptor in the activity of medroxyprogesterone acetate. These medroxyprogesterone acetate exposed mice did not differ morphologically from vehicle treated Tfm mice, indicating that medroxyprogesterone acetate requires androgen receptor to elicit genital tubercle abnormalities.
The increase of progesterone receptor mRNA expression in males and the decrease in females as a result of exposure to medroxyprogesterone acetate, which also causes urethral abnormalities in both sexes, suggests a previously unidentified role for progesterone receptor, possibly interacting with androgen receptor, in anomalous genital tubercle development.

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    • "BPS as well as BPF led to the greatest changes in efficacy on 17␣-OH progesterone and progesterone levels, respectively. Administration of a synthetic progestagen in utero has been associated with virilization of female mice and feminization in male mice (Willingham et al., 2006). Thus, these data indicate that the five analogues, especially BPS and BPF, may have effects which are not prominent for BPA on this endpoint. "
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