Genetic factors contribute strongly to sex hormone levels, yet knowledge of the regulatory mechanisms remains incomplete. Genome-wide association studies (GWAS) have identified only a small number of loci associated with sex hormone levels, with several reproductive hormones yet to be assessed. The aim of the study was to identify novel genetic variants contributing to the regulation of sex hormones. We performed GWAS using genotypes imputed from the 1000 Genomes reference panel. The study used genotype and phenotype data from a UK twin register. We included 2913 individuals (up to 294 males) from the Twins UK study, excluding individuals receiving hormone treatment. Phenotypes were standardised for age, sex, BMI, stage of menstrual cycle and menopausal status. We tested 7 879 351 autosomal SNPs for association with levels of dehydroepiandrosterone sulphate (DHEAS), oestradiol, free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, progesterone, sex hormone-binding globulin and testosterone. Eight independent genetic variants reached genome-wide significance (P<5 × 10−8), with minor allele frequencies of 1.3–23.9%. Novel signals included variants for progesterone (P=7.68 × 10−12), oestradiol (P=1.63 × 10−8) and FAI (P=1.50 × 10−8). A genetic variant near the FSHB gene was identified which influenced both FSH (P=1.74 × 10−8) and LH (P=3.94 × 10−9) levels. A separate locus on chromosome 7 was associated with both DHEAS (P=1.82 × 10−14) and progesterone (P=6.09 × 10−14). This study highlights loci that are relevant to reproductive function and suggests overlap in the genetic basis of hormone regulation.
Spontaneous pain and function-associated pain are prevalent symptoms of multiple acute and chronic muscle pathologies. We established mouse models for evaluating spontaneous pain and bite-evoked pain from masseter muscle, and determined the roles of TRPV1 and the contribution of TRPV1- or NK1-dependent nociceptive pathways. Masseter muscle inflammation increased mouse grimace scale (MGS) scores and face wiping behavior which were attenuated by pharmacological or genetic inhibition of TRPV1. Masseter inflammation led to a significant reduction in bite force. Inhibition of TRPV1 only marginally relieved the inflammation-induced reduction of bite force. These results suggest differential extent of contribution of TRPV1 to the two types of muscle pain. However, chemical ablation of TRPV1-expressing nociceptors or chemogenetic silencing of TRPV1-lineage nerve terminals in masseter muscle attenuated inflammation-induced changes in both MGS scores and bite force. Furthermore, ablation of neurons expressing neurokinin 1 (NK1) receptor in trigeminal subnucleus caudalis also prevented both types of muscle pain. Our results suggest that TRPV1 differentially contribute to spontaneous pain and bite-evoked muscle pain, but TRPV1-expressing afferents and NK1-expressing second order neurons commonly mediate both types of muscle pain. Therefore, manipulation of the nociceptive circuit may provide a novel approach for management of acute or chronic craniofacial muscle pain.
The present study describes a unique way of integrating substrateless electrospinning process with textile technology. We developed a new collector design that provided a pressure-driven, localized cotton-wool structure in free space from which continuous high strength yarns were drawn. An advantage of this integration was that the textile could be drug/dye loaded and be developed into a core-sheath architecture with greater functionality. This method could produce potential nanotextiles for various biomedical applications.
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