transforming-growth-factor-beta and Puberty--Precocious

Puberty represents the transition from an immature to a mature reproductive stage. The mechanisms underlying the onset of normal or precocious puberty have not yet been elucidated. With the goal of gaining an understanding of early events that occur in the testes of precocious animals during this process, a hemigonadectomy was performed on male juvenile sea bass and expression levels of candidate mRNAs were determined through quantitative real-time RT-PCR. For this purpose, the gonadal soma-derived factors gsdf1 and gsdf2, the nuclear receptor 5 subfamily members nr5a1a (ff1b), nr5a1b (ff1d), nr5a2 (ff1a) and nr5a5 (ff1c) and the proliferating cell nuclear antigen or pcna, genes with a putative role in the beginning of spermatogenesis, were isolated and cloned. Hemigonadectomy proved to be a suitable strategy for the study of gonadal stages prior to the appearance of histological differences between precocious and non-precocious fish, as it allowed the subsequent classification of these gonads. The upregulation of the gene encoding the steroidogenic acute regulatory protein (Star) in precocious testes indicates that sex steroids could play a role in the onset of spermatogenesis in sea bass. In contrast, the downregulation observed in ff1b expression indicates that this initial surge in star expression is not the result of Ff1b transactivation, suggesting an alternative pathway for this transcriptional activation. Finally, a decrease in gsdf1 expression in precocious animals suggests that this gene may play a role in the onset of puberty, while its correlation with ff1b expression points to gsdf1 as a putative target for Ff1b-mediated transactivation.

Topics: Animals; Male; Nuclear Reactors; Perciformes; Phosphoproteins; Puberty, Precocious; Reverse Transcriptase Polymerase Chain Reaction; Testis; Transforming Growth Factor beta

Recent genome-wide association (GWA) studies have identified several novel genetic loci associated with age at menarche and age at natural menopause. However, the stringent significance threshold used in GWA studies potentially led to false negatives and true associations may have been overlooked. Incorporating biologically relevant information, we examined whether common genetic polymorphisms in candidate genes of nine groups of biologically plausible pathways and related phenotypes are associated with age at menarche and age at natural menopause. A total of 18,862 genotyped and imputed single nucleotide polymorphisms (SNPs) in 278 genes were assessed for their associations with these two traits among a total of 24,341 women from the Nurses' Health Study (NHS, N = 2,287) and the Women's Genome Health Study (WGHS, N = 22,054). Linear regression was used to assess the marginal association of each SNP with each phenotype. We adjusted for multiple testing within each gene to identify statistically significant SNP associations at the gene level. To evaluate the overall evidence for an excess of statistically significant gene associations over the proportion expected by chance, we applied a one-sample test of proportion to each group of candidate genes. The steroid-hormone metabolism and biosynthesis pathway was found significantly associated with both age at menarche and age at natural menopause (P = 0.040 and 0.011, respectively). In addition, the group of genes associated with precocious or delayed puberty was found significantly associated with age at menarche (P = 0.013), and the group of genes involved in premature ovarian failure with age at menopause (P = 0.025).

Topics: Adolescent; Age Factors; Age of Onset; Child; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Gonadal Steroid Hormones; Humans; Linear Models; Menarche; Menopause; Middle Aged; Nurses; Obesity; Phenotype; Polycystic Ovary Syndrome; Polymorphism, Single Nucleotide; Primary Ovarian Insufficiency; Puberty, Delayed; Puberty, Precocious; Signal Transduction; Smoking; Somatomedins; Thrombophilia; Tobacco Use Disorder; Transforming Growth Factor beta; Women's Health