Aging-related increases in serum sex hormone-binding globulin levels in men might be related to increased synthesis

Previous studies have indicated that serum sex hormone-binding globulin (SHBG) levels increase with age; however, the causes remain unknown. The present study aimed to clarify whether the increase in SHBG levels is attributable to aging-related increases in SHBG synthesis. We examined and evaluated the association of serum SHBG levels with synthesis-related factors in men aged 18–80 years. Additionally, we examined the serum and liver levels of SHBG, hepatic nuclear factor 4α (HNF-4α), and peroxisome proliferator-activated receptor γ (PPAR-γ) in young, middle-aged, and old Sprague–Dawley rats. The study included 209 men in the young group (median age, 33 ± 10 years), 174 men in the middle-aged group (median age, 53 ± 8 years), and 98 men in the elderly group (median age, 71 ± 8 years). Serum SHBG levels increased with age (P < 0.05), whereas HNF-4α and PPAR-γ levels decreased with age (both P < 0.05). Compared with the findings in the young group, the average decline in HNF-4α levels was 2.61 % and 18.46 % in the middle-aged and elderly groups, respectively; the average decreases in PPAR-γ levels in these groups were 12.86 % and 20.76 %, respectively. The results in rats illustrated that liver SHBG and HNF-4α levels increased with age, whereas PPAR-γ and chicken ovalbumin upstream promoter-transcription factor (COUP-TF) levels decreased with age (all P < 0.05). Serum SHBG levels increased in rats with age, whereas HNF-4α and PPAR-γ levels decreased with age (all P < 0.05). The aging-related increased liver levels of the SHBG synthesis promoter HNF-4α and decreased levels of the SHBG inhibitory factors PPAR-γ and COUP-TF suggest that the aging-related increases in SHBG levels are associated with increased SHBG synthesis.