Abstract
BackgroundTTF1 is a transcription factor that is expressed in the hypothalamus after birth and plays crucial roles in pubertal development. TTF1 may regulate the expression of the Kiss1 gene, which may drive puberty onset in the hypothalamic arcuate (ARC) and anterior ventral paraventricular (AVPV) nuclei.MethodsA dual-luciferase reporter assay was used to detect binding between TTF1 and the Kiss1 gene promoter. To investigate the effects of TTF1, we modified TTF1 expression in cell lines and in the ARC or AVPV nucleus of 21-day-old female rats via lentivirus infection. TTF1 and other puberty onset-related genes were detected by qRT-PCR and western blot analyses.ResultsThe in vitro data indicated that TTF1 knockdown (KD) significantly reduced Kiss1 and GnRH expression. Overexpression (OE) of TTF1 promoted Kiss1 expression. In vivo, the expression of Kiss1 and GnRH decreased significantly in the rats with hypothalamic ARC- or AVPV-specific TTF1 KD. The TTF1-KD rats showed vaginal opening delay. H&E staining revealed that the corpus luteum was obviously reduced at the early puberty and adult stages in the rats with ARC- or AVPV-specific TTF1 KD.ConclusionTTF1 bound to the promoter of the Kiss1 gene and enhanced its expression. For 21-day-old female rats, decreased TTF1 in the hypothalamic ARC or AVPV nucleus resulted in delayed vaginal opening and ovarian abnormalities. These observations suggested that TTF1 regulates puberty onset by promoting the expression of Kiss1 and plays an important role in gonad development.
Highlights
Thyroid-specific transcription factor-1 (TTF1) is a transcription factor that is expressed in the hypothalamus after birth and plays crucial roles in pubertal development
Kim et al [20] found that the expression of TTF1 reached a significant peak before puberty onset between postnatal days 26 and 27. These results demonstrated that TTF1 is a central component of the puberty process that might be involved in the central activation of mammalian adolescence
TTF1 knockdown inhibited the expression of Kiss1 and gonadotropin-releasing hormone (GnRH) in ND7–23 cells
Summary
TTF1 is a transcription factor that is expressed in the hypothalamus after birth and plays crucial roles in pubertal development. The ARC is negatively regulated by oestrogen It is responsible for the pulsed release of luteinizing hormone (LH) to form the reproductive cycle, while the AVPV is positively regulated by oestrogen and is responsible for the generation of the preovulatory LH surge that stimulates ovulation [8, 9]. The expression of Kisspeptin in the region around the third ventricle (3 V) is sex biased, and the number of Kiss1-expressing neurons in females is much greater than that in males Researchers hypothesized that this was necessary for the LH surge before ovulation [11,12,13]
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