Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism.

BACKGROUND AND AIMS: Little is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism. METHODS AND RESULTS: Fourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed. CONCLUSIONS: In male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT.

Human leucocytes in asthenozoospermic patients: endothelial nitric oxide synthase expression.

In a basic study at the Andrology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy, we evaluated the pattern of mRNA endothelial nitric oxide synthase (eNOS) expression in human blood leucocytes isolated from normozoospermic fertile and asthenozoospermic infertile men to elucidate any pathogenic involvement in sperm cell motility. Forty infertile men with idiopathic asthenozoospermia and 45 normozoospermic fertile donors, age-matched, were included. Semen parameters were evaluated, and expression analysis of mRNA was performed in human leucocytes using reverse transcription polymerase chain reaction. Sperm volume, count, motility and morphology were determined, and eNOS expression and Western blotting analyses were performed. A positive correlation was observed between the concentrations of NO and the percentage of immotile spermatozoa. The mRNA of eNOS was more expressed in peripheral blood leucocytes isolated from asthenozoospermic infertile men versus those of fertile normozoospermic men (7.46 ± 0.38 versus 7.06 ± 0.56, P = 0.0355). A significant up-regulation of eNOS gene in peripheral blood leucocytes was 1.52-fold higher than that of fertile donors. It is concluded that eNOS expression and activity are enhanced in blood leucocytes in men with idiopathic asthenozoospermia.

Have androgen receptor gene CAG and GGC repeat polymorphisms an effect on sperm motility in infertile men?

Androgens and a normal androgen receptor (AR) are required for normal spermatogenesis. We investigated polyglutamine (CAG) and a polyglycine (GGC) tract in Italian men with defective spermatogenesis. We studied a group of 40 infertile men with spermatogenesis failure without Y-chromosome microdeletions compared with 60 normozoospermic ones. The distributions of both polymorphisms, within the normal range of Caucasian populations, were similar among infertile men and controls. Nonetheless, we observed that the frequency comparison of each CAG allele showed a statistical difference in the allele CAG 22; GGC 17 was the more predominant allele in infertile men than in controls. Moreover, to investigate the hypothesis that semen characteristics are perturbed by androgen receptor allele variants, we tried to detect a link between triplets and sperm motility in all subjects (cases plus controls). Subjects were subdivided into three groups, based on calculated allele frequencies. A significantly decreased motility, related to a longer CAG and GGC tracts, and marked differences between the groups exist for both polymorphisms. Our data highlight a probable relationship between the allele CAG 22/GGC 17 and a defective spermatogenesis in infertile men, suggesting that these polymorphisms might have an important effect on AR function.

Diabetes mellitus-associated periodontitis: differences between type 1 and type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: Although many studies have appeared about diabetes mellitus-associated periodontitis, few have compared periodontitis inflammatory markers between type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and information regarding this issue is scarce and contradictory. We evaluated the levels of plasma C-reactive protein and of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in gingival crevicular fluid in two groups of subjects affected by T1DM and T2DM, in order to identify possible differences between the two classes in the inflammatory mechanisms of diabetes mellitus-associated periodontitis. MATERIAL AND METHODS: Plasma C-reactive protein and gingival crevicular fluid IL-1ß, IL-6 and TNF-α were measured in periodontitis patients affected by type 1 (P-T1DM, n = 24) and type 2 diabetes mellitus (P-T2DM, n = 24). RESULTS: Gingival crevicular fluid levels of IL-1ß and TNF-α in P-T1DM subjects were significantly higher than in P-T2DM subjects. In P-T1DM subjects, we found significant negative correlations between the duration of diabetes mellitus and IL-1ß and between the duration of diabetes mellitus and TNF-α. CONCLUSION: This study shows that IL-1ß and TNF-α levels in periodontitis patients with T1DM are affected by the duration of diabetes mellitus.