Epidemiological and Mendelian Randomization Studies of Dihydrotestosterone and Estradiol and Leukocyte Telomere Length in Men

The Journal of Clinical Endocrinology and Metabolism
Bu B YeapJohn P Beilby

Abstract

Advancing age is accompanied by an accumulation of ill health and shortening of chromosomal telomeres signifying biological aging. T is metabolized to DHT by 5α-reductase (SRD5A2) and to estradiol (E2) by aromatase (CYP19A1). Telomerase preserves telomeres, and T and E2 regulate telomerase expression and activity in vitro. The objective of the study was to establish whether circulating T or its metabolites, DHT or E2, and single-nucleotide polymorphisms in SRD5A2 or CYP19A1 associate with leucocyte telomere length (LTL) in men. Early-morning serum T, DHT, and E2 were assayed using mass spectrometry, and SRD5A2 and CYP19A1 single-nucleotide polymorphisms and LTL analyzed by PCR in 980 men from the Western Australian Busselton Health Survey who participated in the study. LTL was expressed as the T/S ratio. Men were aged (mean ± SD) 53.7 ± 15.6 years. LTL decreased linearly with age, from the T/S ratio of 1.89 ± 0.41 at younger than 30 years to 1.50 ± 0.49 at 70 to younger than 80 years (r = -0.225, P < .0001). After adjustment for age, DHT and E2 were positively correlated with LTL (DHT, r = 0.069, P = .030; E2, r = 0.068, P = .034). The SRD5A2 rs9282858 polymorphism was associated with serum DHT but not with LTL. Three dominant ...Continue Reading

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Citations

May 19, 2016·The New England Journal of Medicine·Danielle M TownsleyNeal S Young
Dec 17, 2016·Human Reproduction Update·D K HapangamaG Saretzki
May 26, 2017·Clinical Endocrinology·Ada S CheungMathis Grossmann
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Oct 31, 2020·Frontiers in Physiology·Jossimara Polettini, Marcia Guimarães da Silva
Jul 11, 2021·Mechanisms of Ageing and Development·Lucía Chico-SordoElisa Varela

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