Characterization of penile androgen receptor expression in micropenis due to hypogonadotropic hypogonadism

The recommendation to treat micropenis with androgen early in infancy and childhood is based on the fact that the normal penile androgen receptor decreases in concentration 2 to 3-fold in early adulthood. Hypothetically the early administration of androgen takes advantage of elevated penile androgen receptor concentration, resulting in optimal penile growth. We verify that there are similar patterns of androgen receptor expression in micropenis and the normal penis.

We used a strain of mice with micropenis due to congenital hypogonadotropic hypogonadism (HPG). Affected mice and normal controls were sacrificed before puberty, and during puberty and early and late adulthood (15, 30, 60 and 90 days, respectively). At autopsy the penis was removed, weighed, pooled and processed for protein extraction. Androgen receptor concentration was determined by Western blot analysis.

In controls penile androgen receptor expression increased 2-fold from before puberty (0.49 fmol./microg. protein) to puberty (0.92 fmol./microg.). At adulthood a 3-fold decrease in penile androgen receptor occurred with the receptor decreasing to 0.33 fmol./microg. in early adulthood and 0.27 fmol./microg. in late adulthood. In HPG animals the penile androgen receptor concentration increased throughout development from 0.20 fmol./microg. before puberty 0.33 fmol./microg. in adulthood.

Androgen receptor expression in the microphallic HPG penis does not mimic normal developmental penile androgen receptor expression. It remains to be elucidated whether hormonal therapy reverses these deficiencies.