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

Pei Xu, Rong Zeng, Qiyou Wan, Yan Xie, Xingyan Liu, Songlin An, Jing Jiang, Jing Yang, Yuanzhong Zhou, Xubo Shen

Experimental gerontology 2023 Aug

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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. Copyright © 2023. Published by Elsevier Inc.

Citation

Pei Xu, Rong Zeng, Qiyou Wan, Yan Xie, Xingyan Liu, Songlin An, Jing Jiang, Jing Yang, Yuanzhong Zhou, Xubo Shen. Aging-related increases in serum sex hormone-binding globulin levels in men might be related to increased synthesis. Experimental gerontology. 2023 Aug;179:112249