Effects of combined growth hormone and testosterone treatments in a rat model of micropenis

Abstract

Although it is well known that penile growth is dependent on androgens, few clinical studies have reported successful treatment of micropenis with testosterone, likely due to concerns regarding the efficacy and safety of prolonged testosterone use. Thus, we assessed the synergenic effects of growth hormone (GH) treatments with and without testosterone on phallic growth in a rat model of micropenis. Fifty Sprague-Dawley rats were assigned to control (C), microphallus (MP), testosterone, GH (G) and GH plus testosterone (GT) treatment groups, and microphallus was induced by secondary hypogonadism. Pre-pubertal treatments with testosterone, GH or the combination were initiated from 7 days after birth and were maintained until 12 weeks of age. To assess the efficacy of treatments, phallic dimensions were determined and histological markers of cavernosal integrity were evaluated. Skeletal and gonadal safety profiles of the treatments were then assessed according to right tibial lengths and testicular weights, respectively. No monotreatments normalised penile dimensions, whereas combination treatments led to complete restoration. The combination treatment also prevented decreases in histological indicators of cavernosal integrity, including smooth muscle actin and collagen III expression levels and fat globule accumulation and sinusoidal density. These synergenic effects of GH treatments on penile growth may follow changes in androgen receptor expression levels and were accompanied by decreased testicular volume losses. Although the physiological conditions of phallic growth differ between humans and rats, this proof-of-concept study provides a strategy for circumventing the problems of testosterone monotherapy for human micropenis.

Keywords: combination treatment; growth hormone; micropenis; testosterone.

Figure 1

Comparisons of stretched penile lengths, penile weights and penile length/right tibial length ratios among the five study groups; comparisons of treatments are made with control (C) and microphallus (MP) groups; *P < 0.05 compared with the MP group; ^#P < 0.05 compared with the C group.

Figure 2

Comparisons of penile androgen receptor (AR) expression between treatment groups; representative traces and corresponding densitometric analyses are presented in upper and lower panels, respectively. Comparisons were made with C and MP groups; *P < 0.05 compared with the MP group; ^#P < 0.05 compared with the C group.

Figure 3

(A) Immunohistochemical localisation of collagens I and III and smooth muscle actin; relative expression levels were determined semiquantitatively; scale bar, 100 μm. (B) Relative expression levels of collagens I and III and sinusoidal densities and the numbers of fat globules; expression data are presented in the densitogram. Comparisons were made with C and MP groups; *P < 0.05, compared with the MP group; ^#P < 0.05 compared with the C group.