title: Testosterone regulates keratin 33B expression in rat penis growth through androgen receptor signaling.
abstract: Androgen therapy is the mainstay of treatment for the hypogonadotropic hypogonadal micropenis because it obviously enhances penis growth in prepubescent microphallic patients. However, the molecular mechanisms of androgen treatment leading to penis growth are still largely unknown. To clarify this well-known phenomenon, we successfully generated a castrated male Sprague Dawley rat model at puberty followed by testosterone administration. Interestingly, compared with the control group, testosterone treatment stimulated a dose-dependent increase of penis weight, length, and width in castrated rats accompanied with a dramatic recovery of the pathological changes of the penis. Mechanistically, testosterone administration substantially increased the expression of androgen receptor (AR) protein. Increased AR protein in the penis could subsequently initiate transcription of its target genes, including keratin 33B (Krt33b). Importantly, we demonstrated that KRT33B is generally expressed in the rat penis and that most KRT33B expression is cytoplasmic. Furthermore, AR could directly modulate its expression by binding to a putative androgen response element sequence of the Krt33b promoter. Overall, this study reveals a novel mechanism facilitating penis growth after testosterone treatment in precastrated prepubescent animals, in which androgen enhances the expression of AR protein as well as its target genes, such as Krt33b.
authors.forename: Yan-Min
authors.initials: YM
authors.lastname: Ma
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dang
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.forename: Xin-Yang
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University; Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People's Republic of China, Xi'an 710061, China.
authors.forename: Da-Lin
authors.initials: DL
authors.lastname: He
authors.affiliation: Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Gong
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D007633:Keratins / Q000378:metabolism*; D008297:Male; D010413:Penis / Q000254:growth & development* / Q000378:metabolism; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013739:Testosterone / Q000502:physiology*
chemical_list: D017931:DNA Primers; D011944:Receptors, Androgen; D013739:Testosterone; D007633:Keratins