406. Regulation of insulin receptor and its substrates by follicle stimulating hormone in granulosa cells

2008 ◽  
Vol 20 (9) ◽  
pp. 86
Author(s):  
J. Taneja ◽  
R. Singh
Keyword(s):  
Insulin Receptor ◽  
Granulosa Cells ◽  
Glycogen Synthesis ◽  
Follicular Development ◽  
Serine Phosphorylation ◽  
Dependent Manner ◽  
Receptor Isoforms ◽  
Insulin Receptor Signalling ◽  
Insulin Receptor Isoforms

Insulin receptor signalling receptor regulates the process of follicular development and maturation, however the regulation of insulin receptor (IR) and its signalling component during folliculogenesis is not well understood. This study demonstrates FSH mediated regulation of insulin receptor isoforms specially IR-B, its substrates and some of the insulin related responses like glycogen synthesis and cell proliferation. There was significant increase in mRNAs expression for insulin receptor (IR) isoforms, IR-A and IR-B in ovary in response to PMSG and in granulosa cells (GCs) in response to FSH. IR protein increased in GCs in response to FSH in a dose and time dependent manner. Interestingly, the expression of mRNAs and proteins for IRS-1 and IRS-2 increased significantly in GCs by FSH. Serine phosphorylation (Ser 636/639) of IRS-1 was decreased by FSH, thus facilitating IRS-1 activation. FSH stimulated glycogen synthesis in a dose dependent manner both by PI 3 kinase dependent and independent pathways. Insulin regulated the amount of FSH stimulated glycogen synthesis by granulosa cells. In contrast, FSH and insulin synergistically stimulated glycogen synthesis GC proliferation which was completely inhibited by LY294002. Knockdown of IRS-1 mRNA by siRNA inhibited FSH stimulated GC proliferation indicating an important role of IRS-1 downstream of FSH. Further research is required to delineate the signalling components involving IRS-1 and IRS-2 in response to FSH and thus involved in the cross-talk between FSH and insulin in GCs. Results thus demonstrate that pituitary FSH regulates insulin receptor and its substrates in rat GCs which might be important for follicular growth and oocyte development.

scholarly journals The Role of Insulin Receptor Isoforms in Diabetes and Its Metabolic and Vascular Complications

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
O. Escribano ◽  
N. Beneit ◽  
C. Rubio-Longás ◽  
A. R. López-Pastor ◽  
A. Gómez-Hernández
Keyword(s):  
Insulin Receptor ◽  
Vascular Complications ◽  
Cell Types ◽  
Metabolic Effects ◽  
Future Research ◽  
Receptor Isoforms ◽  
Insulin Receptor Isoforms ◽  
Treatment Of Diabetes ◽  
Different Cell Types

The insulin receptor (IR) presents by alternative splicing two isoforms: IRA and IRB. The differential physiological and pathological role of both isoforms is not completely known, and it is determinant the different binding affinity for insulin-like growth factor. IRB is more abundant in adult tissues and it exerts mainly the metabolic actions of insulin, whereas IRA is mainly expressed in fetal and prenatal period and exerts mitogenic actions. However, the change in the expression profile of both IR isoforms and its dysregulation are associated with the development of different pathologies, such as cancer, insulin resistance, diabetes, obesity, and atherosclerosis. In some of them, there is a significant increase of IRA/IRB ratio conferring a proliferative and migratory advantage to different cell types and favouring IGF-II actions with a sustained detriment in the metabolic effects of insulin. This review discussed specifically the role of IR isoforms as well as IGF-IR in diabetes and its associated complications as obesity and atherosclerosis. Future research with new IR modulators might be considered as possible targets to improve the treatment of diabetes and its associated complications.

Fibronectin production by chicken granulosa cells in vitro: effect of follicular development

1992 ◽  
Vol 127 (5) ◽  
pp. 466-470 ◽  
Author(s):  
Elikplimi K Asem ◽  
Jacqueline A Carnegie ◽  
Benjamin K Tsang
Keyword(s):  
Granulosa Cells ◽  
Follicular Development ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Ovarian Granulosa Cells ◽  
Preovulatory Follicles ◽  
Vitro Effect ◽  
Dose Dependent

In vitro studies were conducted to investigate the role of chicken ovarian granulosa cells in the production of fibronectin, a component of the basal lamina of ovarian follicles. Collagenase dispersed granulosa cells obtained from the first (F1; about 35 mm in diameter) and third (F3; 15–20 mm in diameter) largest preovulatory follicles, as well as from a pool of small yellow follicles (SF; 6–10 mm in diameter), were incubated in serum-free medium-199 for 24 to 96 h in the absence and presence of luteinizing hormone (LH) or forskolin. Fibronectin secreted in the medium was quantitated by enzyme linked immunosorbent assay. Basal fibronectin production (which increased with the duration of incubation) was significantly greater (p<0.001) in granulosa cells derived from mature follicle (F1) than in F3 or SF cells. Both LH and forskolin stimulated fibronectin production in SF and F3 cells in a dose-dependent manner; however, they were without effect in F1 cells. The magnitude of increase in fibronectin production elicited by LH or forskolin was greater in SF cells than in F3 cells. The cytoplasm of cultured granulosa cells taken at all stages of follicular development stained positively for fibronectin. These findings indicate that chicken granulosa cells produce fibronectin. This ability is acquired early in follicular development and the stimulatory effect of the gonadotropin (LH) diminished as the follicle approached ovulation.

scholarly journals Potential role of insulin receptor isoforms and IGF receptors in plaque instability of human and experimental atherosclerosis

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Nuria Beneit ◽  
José Luis Martín-Ventura ◽  
Carlota Rubio-Longás ◽  
Óscar Escribano ◽  
Gema García-Gómez ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Potential Role ◽  
Experimental Atherosclerosis ◽  
Plaque Instability ◽  
Receptor Isoforms ◽  
Igf Receptors ◽  
Insulin Receptor Isoforms

scholarly journals MicroRNA Mediating Networks in Granulosa Cells Associated with Ovarian Follicular Development

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Baoyun Zhang ◽  
Long Chen ◽  
Guangde Feng ◽  
Wei Xiang ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Granulosa Cells ◽  
Messenger Rna ◽  
Expression Patterns ◽  
Follicular Development ◽  
Functional Networks ◽  
Signal Pathways ◽  
Differentially Expressed Mirnas ◽  
Selection Of

Ovaries, which provide a place for follicular development and oocyte maturation, are important organs in female mammals. Follicular development is complicated physiological progress mediated by various regulatory factors including microRNAs (miRNAs). To demonstrate the role of miRNAs in follicular development, this study analyzed the expression patterns of miRNAs in granulosa cells through investigating three previous datasets generated by Illumina miRNA deep sequencing. Furthermore, via bioinformatic analyses, we dissected the associated functional networks of the observed significant miRNAs, in terms of interacting with signal pathways and transcription factors. During the growth and selection of dominant follicles, 15 dysregulated miRNAs and 139 associated pathways were screened out. In comparison of different styles of follicles, 7 commonly abundant miRNAs and 195 pathways, as well as 10 differentially expressed miRNAs and 117 pathways in dominant follicles in comparison with subordinate follicles, were collected. Furthermore, SMAD2 was identified as a hub factor in regulating follicular development. The regulation of miR-26a/b onsmad2messenger RNA has been further testified by real time PCR. In conclusion, we established functional networks which play critical roles in follicular development including pivotal miRNAs, pathways, and transcription factors, which contributed to the further investigation about miRNAs associated with mammalian follicular development.

scholarly journals Insulin Receptor Isoforms in Cancer

2018 ◽  
Vol 19 (11) ◽  
pp. 3615 ◽  
Author(s):  
Veronica Vella ◽  
Agostino Milluzzo ◽  
Nunzio Scalisi ◽  
Paolo Vigneri ◽  
Laura Sciacca
Keyword(s):  
Insulin Receptor ◽  
Cancer Cells ◽  
Predictive Biomarker ◽  
Point Of View ◽  
Receptor Isoforms ◽  
Insulin Receptor Isoforms ◽  
Target Therapies ◽  
Isoform Expression ◽  
Exon 11 ◽  
Clinical Conditions

The insulin receptor (IR) mediates both metabolic and mitogenic effects especially when overexpressed or in clinical conditions with compensatory hyperinsulinemia, due to the metabolic pathway resistance, as obesity diabetes. In many cancers, IR is overexpressed preferentially as IR-A isoform, derived by alternative splicing of exon 11. The IR-A overexpression, and the increased IR-A:IR-B ratio, are mechanisms that promote the mitogenic response of cancer cells to insulin and IGF-2, which is produced locally by both epithelial and stromal cancer cells. In cancer IR-A, isoform predominance may occur for dysregulation at both mRNA transcription and post-transcription levels, including splicing factors, non-coding RNAs and protein degradation. The mechanisms that regulate IR isoform expression are complex and not fully understood. The IR isoform overexpression may play a role in cancer cell stemness, in tumor progression and in resistance to target therapies. From a clinical point of view, the IR-A overexpression in cancer may be a determinant factor for the resistance to IGF-1R target therapies for this issue. IR isoform expression in cancers may have the meaning of a predictive biomarker and co-targeting IGF-1R and IR-A may represent a new more efficacious treatment strategy.

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