title: Low androgen induced penile maldevelopment involves altered gene expression of biomarkers of smooth muscle differentiation and a key enzyme regulating cavernous smooth muscle cell tone.
abstract: OBJECTIVE
  We determined the effects of low androgens in the neonatal period on biomarkers of smooth muscle cell differentiation, Myh11 and Acta2, and on Pde5A expression in the penis.
  
  
  METHODS
  One-day-old pups were treated daily with the gonadotropin-releasing hormone antagonist antide with or without dihydrotestosterone for 1 to 6 days. Tissues were collected at age day 7 and at adulthood at age 120 days. Penes were examined by quantitative reverse transcriptase-polymerase chain reaction, Western blot and immunohistochemistry. Testes were assayed for the intratesticular testosterone and steroidogenic enzymes Cyp17α1 and StAR.
  
  
  RESULTS
  Gonadotropin-releasing hormone antagonist exposure suppressed the neonatal testicular testosterone surge 70% to 80%. Quantitative reverse transcriptase-polymerase chain reaction revealed 80% to 90% reductions in Cyp17α1 and StAR protein, and 40% to 60% reductions in Myh11 and ACTA2 as a result of gonadotropin-releasing hormone antagonist compared to controls. Dihydrotestosterone co-administration mitigated these decreases. Western blot confirmed the Myh11 decrease at the protein level. Immunohistochemistry of Acta2 confirmed cavernous smooth muscle cell loss at the tissue level. Also, gonadotropin-releasing hormone antagonist exposure decreased Pde5a expression and dihydrotestosterone co-administration mitigated the decrease. Comparison of data between 2 parts of the penis body (corpora cavernosa and corpus spongiosum) showed that antagonist induced decreases in Myh11, Acta2 and Pde5a expression occurred only in the corpora cavernosa, implying that the latter is the target site of low androgen action.
  
  
  CONCLUSIONS
  As evidenced by gonadotropin-releasing hormone antagonist induced suppression of the neonatal testosterone surge and reduced steroidogenesis, low androgens in the neonatal period altered gene expression of biomarkers of smooth muscle cell differentiation. This led to loss of cavernous smooth muscle cells and consequently to penile maldevelopment.
authors: Department of Biomedical Sciences, Tuskegee University, Tuskegee, Alabama.
authors: Lilian A
authors: LA
authors: Okumu
authors: Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, Alabama.
authors: Tim D
authors: TD
authors: Braden
authors: Department of Biomedical Sciences, Tuskegee University, Tuskegee, Alabama.
authors: Krystal
authors: K
authors: Vail
authors: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors: Liz
authors: L
authors: Simon
authors: Department of Biomedical Sciences, Tuskegee University, Tuskegee, Alabama. Electronic address: goyalho@mytu.tuskegee.edu.
authors: Hari Om
authors: HO
authors: Goyal
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000728:Androgens / Q000172:deficiency*; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D002454:Cell Differentiation; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology* / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D010413:Penis / Q000002:abnormalities* / Q000254:growth & development*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins; D000728:Androgens; D015415:Biomarkers; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D018995:Myosin Heavy Chains; C000595077:Myh11 protein, rat; C517384:Pde5a protein, rat; C498862:Acta2 protein, rat
keywords: Pde5a protein; androgens; animals; growth and development; newborn; penis; rat