Exon 1 of AR gene contains a variable number of CAG triplets, which encode a polyglutamine stretch of variable length in the N-terminal domain of the receptor. Experimental evidence has accumulated in demonstrating that the length of this stretch influences AR transcriptional activity and therefore modulates target organs responsiveness to androgens. Aim of our study was to evaluate CAG repeats length [(CAGr)n] in various conditions hypothetically influenced by AR function. 35 infertile, 32 hypoandrogenized (hypo) patients (absent beard and body hair, reduced epididymal and prostate size, recurvatum, etc.) and 91 normal controls (all fathers, normal muscle and bone structure, normal body hair) were analysed. Y-microdeletions and other congenital abnormalities were excluded in infertile patients. DNA was extracted from blood and amplified by PCR using the primers flanking the CAG repeat in the AR gene. PCR products were electrophoresed on the autosequencer to determine the exact (CAGr)n.
The normal Caucasian population (subject from Central Italy), is super imposable to other European population for (CAGr)n distribution. Hypoandrogenetic status is characterized by an increased number of CAG repeats; conversely, infertile patients are not statistically different from the control group (see Table 1).
T levels do not correlate to (CAGr)n. Prostate size is significantly different between hypo and controls (P<0.003).
In conclusion, given the same amount of circulating testosterone (as in hypoandrogenized and control group), the final net androgenic phenotypical effect is due to AR polymorphism.
01 - 05 Apr 2006
European Society of Endocrinology