Steroid receptors and mammalian penile development: An unexpected role for progesterone receptor?
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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ABSTRACT: As modern society has became more open, interest in healthy internal and external growth has increased, including that pertaining to penile length in children. A micropenis is defined as one where penile length is more than 2 SD (standard deviation) below the mean, and it can be traced back to chromosome and endocrine disorders. The authors executed this study to suggest guidelines for the study of the micropenis and standard information for penile length in Korean newborns.Korean Journal of Pediatrics 01/2008; 51(9). DOI:10.3345/kjp.2008.51.9.944
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ABSTRACT: Background: Bisphenol A (BPA) is a chemical with widespread human exposure suspected of causing low-dose effects. Thus a need for developing alternatives to BPA exists. Structural analogues of BPA have already been detected in foods and humans. Due to the structural analogy of the alternatives there is a risk of effects similar to BPA.Objectives: The aim was to elucidate and compare the hazards of BPB, BPE, BPF, BPS and 4-cumylphenol (HPP) to BPA.Methods: In vitro studies on steroidogenesis, receptor activity, and biomarkers of effect, as well as QSAR modeling.Results: All test compounds caused the same qualitative effects on estrogen receptor and androgen receptor activity, and most of the alternatives exhibited potencies within the same range as BPA. Hormone profiles for the compounds indicated a specific mechanism of action on steroidogenesis generally leading to decreased androgen, and increased estrogen and progestagen levels. Differential effects on corticosteroid synthesis were observed suggesting a compound specific mechanism. Overall BPS was less estrogenic and antiandrogenic than BPA, but BPS showed the largest efficacy on 17α-OH progesterone. Finally there were indications of DNA damage, carcinogenicity, oxidative stress, effects on metabolism and skin sensitization of one or more of the test compounds.Conclusions: Interference with the endocrine system was the predominant effect of the test compounds. A substitution of BPA with these structural analogues should be carried out with caution.Toxicological Sciences 02/2014; 139(1). DOI:10.1093/toxsci/kfu030 · 4.48 Impact Factor