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Biography

Lilian Okumu completed her PhD from University College Dublin, Ireland, and postdoctoral fellowship from Tuskegee University’s Center for Veterinary Medicine, Nursing and Allied Health in 2013. Currently, she is an assistant professor of Biology at Tuskegee University.

Abstract

Previously we showed that exposure of neonatal rats to estrogens and anti-androgens at a critical time period induced penile mal-development, characterized by accumulation of fat cells and loss of smooth muscle cells in the corpus cavernosum. This study aimed to determine the cellular and molecular changes characterizing the above effects. Pups were treated daily with GnRH antagonist antide or diethylstilbestrol (DES), with or without androgen receptor (AR) agonist dihydrotestosterone (DHT) or estrogen receptor (ESR) antagonist ICI 182,780, for postnatal days 1-6. Tissues were collected at days 7, 10, 21 or adulthood. Testicular testosterone (T) was assayed and microarray performed on the 7-day old penile and testicular samples. Real-time-PCR was used to quantify expression of Ar, Esr1, Esr2, Pparg, Pde5a, Myh11 and Acta2. PDE5A, MYH11 and ACTA2 protein levels were determined by western blot and/or immunohistochemistry (IHC). Both estrogens and anti-androgens induced similar effects. Intratesticular T surge was decreased by 80-90%. The reduction was mitigated by ICI but not DHT co-administration. Microarray showed significant down-regulation of smooth muscle cell markers (Myh11, Myh7, Mylk, and Actg2) in the penis and steroidogenic enzymes (Hsd3β1, Cyp11α1, Cyp17α1 and Cyp2c22) and Star protein in the testis. Real-time PCR showed 50-70% reduction in Myh11 and Pde5a, which was confirmed by Western blots. ACTA2 IHC showed reduction in the number and size of corpus cavernosum’s sinusoids. Contrastingly, Pparg and Esr1 expression was up-regulated, while that for Esr2 and Ar was unaltered. These results provide evidence that estrogen-induced penile mal-development is mediated via ESR1 and AR pathways.

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