IGF-1 Influences Gonadotropin-Releasing Hormone Regulation of Puberty

Dees, W. Les; Hiney, Jill K.; Srivastava, Vinod K.

doi:10.1159/000514217

Cited by 35 publications

(21 citation statements)

References 122 publications

(177 reference statements)

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“…GnRH perikarya express IGF-1R before puberty in mice, suggesting a potential direct anatomical locus where IGF-1 can control reproductive development and function 33 , 35 . Furthermore, the action of IGF-1 on IGF-1R in GnRH neurons regulates the onset of puberty in rodents 36 , 37 .…”

Section: Discussionmentioning

confidence: 99%

Involvement of IGF-1R-PI3K-AKT-mTOR pathway in increased number of GnRH3 neurons during androgen-induced sex reversal of the brain in female tilapia

Oda

Inoue

Kaneko

et al. 2022

Sci Rep

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The neuroplastic mechanism of sex reversal in the fish brain remains unclear due to the difficulty in identifying the key neurons involved. Mozambique tilapia show different reproductive behaviours between sexes; males build circular breeding nests while females hold and brood fertilized eggs in their mouth. In tilapia, gonadotropin-releasing hormone 3 (GnRH3) neurons, located in the terminal nerve, regulate male reproductive behaviour. Mature males have more GnRH3 neurons than mature females, and these neurons have been indicated to play a key role in the androgen-induced female-to-male sex reversal of the brain. We aimed to elucidate the signalling pathway involved in the androgen-induced increase in GnRH3 neurons in mature female tilapia. Applying inhibitors to organotypic cultures of brain slices, we showed that the insulin-like growth factor (IGF)-1 receptor (IGF-1R)/PI3K/AKT/mTOR pathway contributed to the androgen-induced increase in GnRH3 neurons. The involvement of IGF-1 and IGF-1R in 11-ketotestosterone (11-KT)-induced development of GnRH3 neurons was supported by an increase in Igf-1 mRNA shortly after 11-KT treatment, the increase of GnRH3 neurons after IGF-1 treatment and the expression of IGF-1R in GnRH3 neurons. Our findings highlight the involvement of IGF-1 and its downstream signalling pathway in the sex reversal of the tilapia brain.

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Section: Discussionmentioning

confidence: 99%

Involvement of IGF-1R-PI3K-AKT-mTOR pathway in increased number of GnRH3 neurons during androgen-induced sex reversal of the brain in female tilapia

Oda

Inoue

Kaneko

et al. 2022

Sci Rep

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“…IGF-1, which modulates the expression of the KISS1 gene, plays an important role in pubertal onset [ 50 ]. A significant increase in serum IGF-1 close to the onset of puberty can induce prepubertal GnRH secretion and advance the timing of puberty [ 51 ]. IGF-binding protein 3 (IGFBP-3) mainly transports IGFs in the plasma.…”

Section: Discussionmentioning

confidence: 99%

Gene Polymorphisms Associated with Central Precocious Puberty and Hormone Levels in Chinese Girls

Chen

et al. 2022

International Journal of Endocrinology

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Central precocious puberty (CPP) is associated with adverse health outcomes in females; however, CPP pathogenesis remains unclear. In this study, we investigated the association of 20 single nucleotide polymorphisms (SNPs) in eight genes with CPP risk and hormone levels. A case-control study on 247 and 243 girls with and without CPP, respectively, was conducted at Kunming Children’s Hospital, China, from September 2019 to August 2020. The genotype of the SNPs and their haplotypes were identified. Additionally, the effects of the polymorphisms on hormone levels were investigated. Three variants (rs10159082, rs7538038, and rs5780218) in KISS1 and two variants (rs7895833 and rs3758391) in SIRT1 were related to an increased CPP risk (odds ratio (OR) = 1.524, 1.507, 1.409, 1.348, and 1.737; 95% confidence interval (CI) = 1.176–1.974, 1.152–1.970, 1.089–1.824, 1.023–1.777, and 1.242–2.430, respectively). Rs3740051in SIRT1 and rs1544410 in VDR reduced CPP risk (OR = 0.689, 0.464; 95% CI, 0.511–0.928, 0.232–0.925, respectively). Rs1544410, rs7975232, and rs731236 in VDR were negatively correlated with peak follicle-stimulating hormone (FSH; β = −2.181; P = 0.045 ), basal FSH (β = −0.391; P = 0.010 ), and insulin-like growth factor (β = −50.360; P = 0.041 ) levels, respectively. KISS1, SIRT1, and VDR variants were associated with CPP susceptibility, and VDR SNPs influenced hormonal levels in Chinese females with CPP. In particular, VDR polymorphism rs1544410 was associated with both CPP risk and GnRH-stimulated peak FSH levels. Further functional research and large-scale genetic studies of these loci and genes are required to confirm our findings.

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“…In addition, it has emerged as a prime candidate for having a significant role in the onset of puberty. IGF-1 may promote the secretion of prepubertal GnRH, and the level of IGF-1 increases in the circulation as puberty approaches, which can advance the timing of puberty ( Dees et al, 2021 ). Multiple findings suggested that IGF-1 may prime pituitary gonadotrophs and stimulate the synthesis of GnRHR and FSH during puberty onset in prepubertal salmon.…”

Section: Discussionmentioning

confidence: 99%

Effects of Fuyou Formula on GnRH Secretion and Related Gene Expression in Treating Precocious Puberty

et al. 2022

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The Fuyou (Fy) formula is an in-hospital preparation consisting of traditional Chinese medicine (TCM) that has been used for treating precocious puberty (PP) for more than 20 years. In this study, we aimed to clarify the effect of the Fy formula and its major components on PP. To confirm the effect of the Fy formula on the release of hypothalamic gonadotropin-releasing hormone (GnRH), GT1-7 cells were treated with estrogen to build the model group and subsequently treated with the Fy formula and its major components to explore their effects on the secretion of GnRH. The level of GnRH in GT1-7 cells was determined using enzyme-linked immunosorbent assay. The results illustrated that, compared to the model group, the Fy formula inhibited the release of GnRH. In addition, the expression levels of proteins related to GnRH secretion, including GnRH, gonadotropin-releasing hormone receptor (GnRHR), Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), estrogen receptor α (ERα), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-1 receptor (IGF-1R), were detected by real-time polymerase chain reaction (RT-qPCR). The results demonstrated that the Fy formula significantly reduced the level of GnRH secretion in the GT1-7 cell lines compared with the model group. Moreover, it significantly downregulated the expression of GnRH, GnRHR, Kiss1, GPR54, ERα, IGF-1, and IGF-1R. In summary, our results indicate that the Fy formula and its major components may inhibit the effects of estrogen, which alleviates PP through transcriptional regulation of target genes.

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IGF-1 Influences Gonadotropin-Releasing Hormone Regulation of Puberty

Cited by 35 publications

References 122 publications

Involvement of IGF-1R-PI3K-AKT-mTOR pathway in increased number of GnRH3 neurons during androgen-induced sex reversal of the brain in female tilapia

Involvement of IGF-1R-PI3K-AKT-mTOR pathway in increased number of GnRH3 neurons during androgen-induced sex reversal of the brain in female tilapia

Gene Polymorphisms Associated with Central Precocious Puberty and Hormone Levels in Chinese Girls

Effects of Fuyou Formula on GnRH Secretion and Related Gene Expression in Treating Precocious Puberty

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