Insulin-like growth factor-1 (IGF-1) promotes primordial follicle growth and reduces DNA fragmentation through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signalling pathway

2018 ◽  
Vol 30 (11) ◽  
pp. 1503 ◽  
Author(s):  
Maria É. S. Bezerra ◽  
Ricássio S. Barberino ◽  
Vanúzia G. Menezes ◽  
Bruna B. Gouveia ◽  
Taís J. S. Macedo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Dna Fragmentation ◽  
Protein Kinase B ◽  
Primordial Follicle ◽  
Akt Pathway ◽  
Insulin Like Growth Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

We investigated the effects of insulin-like growth factor 1 (IGF-1) on the morphology and follicular activation of ovine preantral follicles cultured in situ and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway is involved in IGF-1 action in the sheep ovary. Ovine ovarian fragments were fixed for histological and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) analyses (fresh control) or cultured in supplemented alpha-minimum essential medium (α-MEM+; control) or α-MEM+ with IGF-1 (1, 10, 50, 100 or 200 ng mL−1) for 7 days. Follicles were classified as normal or atretic, primordial or growing and the oocyte and follicle diameters were measured. DNA fragmentation was evaluated by TUNEL assay. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was performed on the fresh control, α-MEM+ and 100 ng mL−1 IGF-1 samples. Inhibition of PI3K activity was performed through pretreatment with the PI3K inhibitor LY294002 and phosphorylated AKT (pAKT) expression was analysed after culture in the absence or presence of LY294002. IGF-1 at 100 ng mL−1 increased (P < 0.05) follicular activation compared with α-MEM+ and decreased TUNEL-positive cells (P < 0.05) compared with other treatments. PCNA-positive cells also increased (P < 0.05) in 100 ng mL−1 IGF-1. LY294002 significantly inhibited follicular activation stimulated by α-MEM+ and 100 ng mL−1 IGF-1 and reduced pAKT expression in follicles. Overall, IGF-1 at 100 ng mL−1 promoted primordial follicle activation, cell proliferation and reduced DNA fragmentation after in situ culture through the PI3K/AKT pathway.

scholarly journals Vitamin D3 Activates Phosphatidylinositol-3-Kinase/Protein Kinase B via Insulin-Like Growth Factor-1 to Improve Testicular Function in Diabetic Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Yanyan He ◽  
Yang Liu ◽  
Qing-Zhu Wang ◽  
Feng Guo ◽  
Fengjuan Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Diabetic Rats ◽  
Testicular Function ◽  
Insulin Like Growth Factor ◽  
Wild Type ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

Objective. In diabetes mellitus, vitamin D3 deficiency affects sex hormone levels and male fertility; however, the mechanism leading to the disorder is unclear. This research was designed to investigate the mechanism of vitamin D3 deficiency and hypogonadism in diabetic rats. Our aim was to assess serum vitamin D3 levels and the relationship among vitamin D3, insulin-like growth factor-1 (IGF-1), and testicular function. Materials and Methods. Rats with streptozotocin-induced diabetes were randomly divided into four groups and treated with different doses of vitamin D3: no vitamin D3, low (0.025 μg/kg/day), high (0.1 μg/kg/day), and high (0.1 μg/kg/day) with JB-1 (the insulin-like growth factor-1 receptor inhibitor group, 100 μg/kg/day). The groups were compared with wild-type rats, which function as the control group. Various parameters such as vitamin D3 and IGF-1 were compared between the experimental and wild-type groups, and their correlations were determined. Results. Twelve weeks of vitamin D3 supplementation improved the testosterone levels, as shown by the increase in the level of serum IGF-1 in diabetic rats. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), which was a downstream of the signaling pathway of IGF-1, was significantly increased after vitamin D3 treatment. Conclusions. The study shows that vitamin D3 may promote the expression of testosterone and improve testicular function in diabetic rats by activating PI3K/AKT via IGF-1.

scholarly journals Cancer Cell-Derived Clusterin Modulates the Phosphatidylinositol 3′-Kinase-Akt Pathway through Attenuation of Insulin-Like Growth Factor 1 during Serum Deprivation

2008 ◽  
Vol 28 (13) ◽  
pp. 4285-4299 ◽  
Author(s):  
Hakryul Jo ◽  
Yonghui Jia ◽  
Kulandayan K. Subramanian ◽  
Hidenori Hattori ◽  
Hongbo R. Luo
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Cancer Cell ◽  
Regulatory System ◽  
Serum Deprivation ◽  
Akt Pathway ◽  
Growth Factor Signaling ◽  
Insulin Like Growth Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

ABSTRACT Cancer cells in their respective microenvironments must endure various growth-constraining stresses. Under these conditions, the cancer cell-derived factors are thought to modulate the signaling pathways between cell growth and dormancy. Here, we describe a cancer cell-derived regulatory system that modulates the phosphatidylinositol 3′-kinase (PI3K)-Akt pathway under serum deprivation stress. Through the use of biochemical purification, we reveal that cancer cell-secreted insulin-like growth factor 1 (IGF-1) and clusterin, an extracellular stress protein, constitute this regulatory system. We show that secreted clusterin associates with IGF-1 and inhibits its binding to the IGF-1 receptor and hence negatively regulates the PI3K-Akt pathway during serum deprivation. This inhibitory function of clusterin appears to prefer IGF-1, as it fails to exert any effects on epidermal growth factor signaling. We demonstrate furthermore that the constitutive activation of oncogenic signaling downstream of IGF-1 confers insensitivity to the inhibitory effects of clusterin. Thus, the interplay between cancer cell-derived clusterin and IGF-1 may dictate the outcome of cell growth and dormancy during tumorigenic progression.

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