Micropenis in hypogonadotropic hypogonadism: Response of the penile androgen receptor to testosterone treatment

Purpose: We determine whether testosterone therapy alters penile androgen receptor expression within the hypogonadotropic hypogonadal (HPG) micropenis. Materials and Methods: In protocol 1 a strain of mice with micropenis due to congenital HPG and wild type litter mates were divided into testosterone treated and untreated groups. Treatment was initiated on day 15 of life. On day 90 of life (day 75 of treatment) the mice were sacrificed, and the penises were removed and weighed. In protocol 2 microphallic mice treated with testosterone were sacrificed on days 0, 6, 30, 60 and 75 after the initiation of treatment. Untreated HPG and wild type litter mates served as controls. At autopsy the penis was removed and weighed, and androgen receptor content was determined by Western immunoblotting. Results: Testosterone treatment resulted in 6-fold up regulation in HPG penile androgen receptor, approximately 1.4-fold higher than in the normal wild type pubescent penis. Testosterone induced and wild type pubescent penile androgen receptor up regulation was maintained for approximately 75 and 60 days, respectively. Despite improved HPG penile androgen receptor expression penile growth did not become normal. Average total penile weight plus or minus standard deviation was 7.2 ± 3.5 mg. in untreated HPG mice. Testosterone significantly improved average HPG penile weight to 23.5 ± 1.8 mg. (p <0.001). However, the testosterone treated micropenis failed to reach average normal penile size (38.6 ± 2.6 mg., p <0.001). Conclusions: Testosterone increases the concentration and duration of penile androgen receptor expression within the HPG micropenis. Despite this improvement microphallic HPG penile growth does not become normal.