title: Steroid receptors and mammalian penile development: an unexpected role for progesterone receptor?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for the Study and Treatment of Hypospadias, Department of Urology, School of Medicine, University of California, San Francisco, 94143, USA. ewillingham@casmail.ucsf.edu
authors.forename: Emily
authors.initials: E
authors.lastname: Willingham
authors.forename: Koray
authors.initials: K
authors.lastname: Agras
authors.forename: Antonio E P
authors.initials: AE
authors.lastname: de Souza
authors.forename: Ramdev
authors.initials: R
authors.lastname: Konijeti
authors.forename: Selcuk
authors.initials: S
authors.lastname: Yucel
authors.forename: William
authors.initials: W
authors.lastname: Rickie
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Cunha
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Baskin
mesh_terms: D000818:Animals; D005260:Female; D005836:Genitalia, Female / Q000002:abnormalities* / Q000254:growth & development*; D008297:Male; D051379:Mice; D010413:Penis / Q000002:abnormalities* / Q000254:growth & development*; D011944:Receptors, Androgen / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D011980:Receptors, Progesterone / Q000502:physiology*
chemical_list: D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone