Effect of polymorphisms in selected genes involved in pituitary-testicular function on reproductive hormones and phenotype in aging men

Huhtaniemi, I. et al. (2010) Effect of polymorphisms in selected genes involved in pituitary-testicular function on reproductive hormones and phenotype in aging men. Journal of Clinical Endocrinology and Metabolism, 95(4), pp. 1898-1908.

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Abstract

Context: Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men. Objective: We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status. Design and Setting: Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men. Participants: A total of 2748 men, aged 40–79 (mean ± SD, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor- and -β (ESR1 and ESR2), steroid 5 -reductase type II (SRD5A2), 17 -hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH β-subunit (LHB), and LH receptor (LHCGR). Main Outcome Measures: We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action. Results: Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition). Conclusion: In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lean, Professor Michael
Authors: Huhtaniemi, I., Pye, S., Holliday, K., Thomson, W., O'Neill, T., Platt, H., Payne, D., John, S., Jiang, M., Bartfai, G., Boonen, S., Casanueva, F., Finn, J., Forti, G., Giwercman, A., Han, T., Kula, K., Lean, M., Pendleton, N., Punab, M., Silman, A., Vanderschueren, D., and Wu, F.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
Journal Name:Journal of Clinical Endocrinology and Metabolism
Publisher:The Endocrine Society
ISSN:0021-972X
ISSN (Online):1945-7197
Published Online:19 February 2010

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