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Environmental and genetic contributors to salivary testosterone levels in infants.

ABSTRACT: Transient activation of the hypothalamic-pituitary-gonadal axis in early infancy plays an important role in male genital development and sexual differentiation of the brain, but factors contributing to individual variation in testosterone levels during this period are poorly understood. We measured salivary testosterone levels in 222 infants (119 males, 103 females, 108 singletons, 114 twins) between 2.70 and 4.80?months of age. We tested 16 major demographic and medical history variables for effects on inter-individual variation in salivary testosterone. Using the subset of twins, we estimated genetic and environmental contributions to salivary testosterone levels. Finally, we tested single nucleotide polymorphisms (SNPs) within ±5?kb of genes involved in testosterone synthesis, transport, signaling, and metabolism for associations with salivary testosterone using univariate tests and random forest (RF) analysis. We report an association between 5?min APGAR scores and salivary testosterone levels in males. Twin modeling indicated that individual variability in testosterone levels was primarily explained by environmental factors. Regarding genetic variation, univariate tests did not reveal any variants significantly associated with salivary testosterone after adjusting for false discovery rate. The top hit in males was rs10923844, an SNP of unknown function located downstream of HSD3B1 and HSD3B2. The top hits in females were two SNPs located upstream of ESR1 (rs3407085 and rs2295190). RF analysis, which reflects joint and conditional effects of multiple variants, indicated that genes involved in regulation of reproductive function, particularly LHCGR, are related to salivary testosterone levels in male infants, as are genes involved in cholesterol production, transport, and removal, while genes involved in estrogen signaling are related to salivary testosterone levels in female infants.

SUBMITTER: Xia K

PROVIDER: S-EPMC4214198 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Environmental and genetic contributors to salivary testosterone levels in infants.

Xia Kai K Yu Yang Y Ahn Mihye M Zhu Hongtu H Zou Fei F Gilmore John H JH Knickmeyer Rebecca C RC

Frontiers in endocrinology 20141030

Transient activation of the hypothalamic-pituitary-gonadal axis in early infancy plays an important role in male genital development and sexual differentiation of the brain, but factors contributing to individual variation in testosterone levels during this period are poorly understood. We measured salivary testosterone levels in 222 infants (119 males, 103 females, 108 singletons, 114 twins) between 2.70 and 4.80 months of age. We tested 16 major demographic and medical history variables for ef ...[more]

PMID: 25400620

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Project description:INTRODUCTION:Recently, testosterone (T) has been shown to be associated with premature ejaculation (PE) symptoms in the literature. Furthermore, studies suggest that the etiology of PE is partly under genetic control. AIM:The aim of this study was to reassess findings suggesting an association between testosterone (T) and a key symptom of PE, ejaculation latency time (ELT), as well as exploratively investigating associations between six androgen-related genetic polymorphisms and ELT. MATERIALS AND METHODS:Statistical analyses were performed on a population-based sample of 1,429 Finnish men aged 18-45 years (M = 26.9, SD = 4.7). Genotype information was available for 1,345-1,429 of these (depending on the polymorphism), and salivary T samples were available from 384 men. Two androgen receptor gene-linked, two 5-alpha-reductase type 2-gene-linked, and two sex hormone-binding globuline gene-linked polymorphisms were genotyped. MAIN OUTCOME MEASURES:Ejaculatory function was assessed using self-reported ELT. RESULTS:We found no association between salivary T levels and ELT. We found a nominally significant association between a 5-alpha-reductase type 2-gene-linked polymorphism (rs2208532) and ELT, but this association did not remain significant after correction for multiple testing. One single nucleotide polymorphism in the sex hormone-binding globulin gene (rs1799941) moderated (significantly after correction for multiple testing) the association between salivary T and ELT, so that A:A genotype carriers had significantly lower salivary T levels as a function of increasing ELT compared with other genotype groups. CONCLUSIONS:We were unable to find support for the hypothesis suggesting an association between T levels and ELT, possibly because of the low number of phenotypically extreme cases (the sample used in the present study was population based). Our results concerning genetic associations should be interpreted with caution until replication studies have been conducted. Jern P, Westberg L, Ankarberg-Lindgren C, Johansson A, Gunst A, Sandnabba NK, and Santtila P. Associations between salivary testosterone levels, androgen-related genetic polymorphisms, and self-estimated ejaculation latency time. Sex Med 2014;2:107-114.

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Environmental and genetic contributors to salivary testosterone levels in infants.

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Environmental and genetic contributors to salivary testosterone levels in infants.

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