A 5α‐reductase (SRD5A2) polymorphism is associated with serum testosterone and sex hormone–binding globulin in men, while aromatase (CYP19A1) polymorphisms are associated with oestradiol and luteinizing hormone reciprocally

Abstract

Summary Context Pituitary luteinizing hormone (LH) stimulates testicular production of testosterone (T) which is metabolized to dihydrotestosterone (DHT) by 5α‐reductase and to oestradiol (E2) by aromatase. How the activity of population variants in these enzymes impacts on gonadal function is unclear. We examined whether polymorphisms in 5α‐reductase (SRD5A2) and aromatase (CYP19A1) genes predict circulating sex hormone concentrations. Design Cross‐sectional analysis of 1865 community‐dwelling men aged 50.4 ± 16.8 years. Measurements Early morning sera assayed for T, DHT and E2 (mass spectrometry), and SHBG and LH (immunoassay). Two SRD5A2 and eleven CYP19A1 polymorphisms were analysed by PCR. Regression models were adjusted for age and cardiometabolic risk factors. Results SRD5A2 polymorphism rs9282858 GA vs. GG was associated with higher serum T (+1.5 nmol/L, P < 0.001) and higher SHBG (+3.3 nmol/L, P = 0.001). CYP19A1 polymorphisms were associated with higher serum E2 and lower LH in reciprocal fashion, from which the two‐copy haplotype rs10046 = T/rs2899470 = G/rs11575899 = I/rs700518 = G/rs17703883 = T was associated with higher E2 (63.4 vs. 56.5 pmol/L, P = 0.001) and lower LH (3.9 vs. 4.5 IU/L, P = 0.001) compared to null copies. Conversely, rs10046 = C/rs2899470 = T/rs11575899 = D/rs700518 = A/rs17703883 = C was associated with lower E2 (51.8 vs. 62.0 pmol/L, P = 0.001) and higher LH (5.7 vs. 3.9 IU/L, P < 0.001). These haplotypes were associated primarily with differences in E2 in men <65 years and LH in men ≥65 years. Conclusions A 5α‐reductase polymorphism predicts circulating T and SHBG, while aromatase polymorphisms predict E2 and LH in reciprocal fashion. Age and aromatase polymorphisms interact to affect E2 and LH. How these functional polymorphisms impact on male reproductive and general health outcomes requires further study.

The Relationship of Steroid Hormones, Genes Related to Testosterone Metabolism and Behavior in Boys With Autism in Slovakia

“…In addition, rs9282858 was also shown to predict serum testosterone and SHBG levels in adult men, where GA carriers had higher serum testosterone and SHBG levels than GG carriers. 46 This result corresponds to our findings in ASD boys, where GG carriers showed stronger RRBs and stronger RRBs were shown to be related to lower SHBG levels.…”

Reversibility in male idiopathic osteoporosis possible

“…The result of the genetic analysis raises the question of the possible causal effect of these polymorphisms in lowering aromatase function and, consequently, serum E 2 . Recently, several genetic studies have demonstrated an association between some aromatase polymorphisms and lower levels of serum E 2 in men ( 20 , 21 , 22 ). Even though none of the SNPs and/or polymorphisms found in our patient and his cousin are known to be related to aromatase dysfunction, it is possible that one or more of them may be at the basis of their observed low serum E 2 .…”