Effects of Local and Sustained Release of FGF, IGF, and GH on Germ Cells in Unilateral Undescended Testis in Rats

Bingöl-Koloğlu, Meltem; Bahadır, Gökhan Berktuğ; Vargun, Rahsan; İlkay, Hande; Bagriacik, Emin Umit; Yolbakan, Sultan; Güven, Cengiz; Endoğan, Tuğba; Hasırcı, Nesrin; Dindar, Hüseyin

doi:10.1016/j.urology.2009.04.017

Cited by 15 publications

(12 citation statements)

References 31 publications

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“…Zebrafish models have shown that the IGF1Rb isoform is required for proper migration and maintenance of PGC numbers until they reach the genital ridge . Notably, IGF signalling is also required for maintaining the germ cell population in postnatal mice with unilateral undescended testis in both the affected testis and the contralateral descended testis . Blockade of IGF1R signalling or the downstream PI3K pathway resulted in loss of pluripotency in murine neonatal spermatogonial stem cells which is maintained by IGF1 produced by the Leydig cells in vivo .…”

Section: Discussionmentioning

confidence: 99%

IGF1R signalling in testicular germ cell tumour cells impacts on cell survival and acquired cisplatin resistance

Selfe

Goddard

McIntyre

et al. 2018

The Journal of Pathology

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Testicular germ cell tumours (TGCTs) are the most frequent malignancy and cause of death from solid tumours in the 20‐ to 40‐year age group. Although most cases show sensitivity to cis‐platinum‐based chemotherapy, this is associated with long‐term toxicities and chemo‐resistance. Roles for receptor tyrosine kinases other than KIT are largely unknown in TGCT. We therefore conducted a phosphoproteomic screen and identified the insulin growth factor receptor‐1 (IGF1R) as both highly expressed and activated in TGCT cell lines representing the nonseminomatous subtype. IGF1R was also frequently expressed in tumour samples from patients with nonseminomas. Functional analysis of cell line models showed that long‐term shRNA‐mediated IGF1R silencing leads to apoptosis and complete ablation of nonseminoma cells with active IGF1R signalling. Cell lines with high levels of IGF1R activity also showed reduced AKT signalling in response to decreased IGF1R expression as well as sensitivity to the small‐molecule IGF1R inhibitor NVP‐AEW541. These results were in contrast to those in the seminoma cell line TCAM2 that lacked IGF1R signalling via AKT and was one of the two cell lines least sensitive to the IGF1R inhibitor. The dependence on IGF1R activity in the majority of nonseminomas parallels the known role of IGF signalling in the proliferation, migration, and survival of primordial germ cells, the putative cell of origin for TGCT. Upregulation of IGF1R expression and signalling was also found to contribute to acquired cisplatin resistance in an in vitro nonseminoma model, providing a rationale for targeting IGF1R in cisplatin‐resistant disease. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

IGF1R signalling in testicular germ cell tumour cells impacts on cell survival and acquired cisplatin resistance

Selfe

Goddard

McIntyre

et al. 2018

The Journal of Pathology

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“…Mice carrying a transgene‐expressing IGFBP1 exhibited defects in spermatogenesis with altered production and quality of spermatozoa, attributed to the lack of bio‐available IGF1 caused by increased binding of IGFBP1 (Froment et al ., ). IGF1 administration was able to reverse the decrease in germ cell numbers observed in rats with surgically induced unilateral undescended testes (Bingol‐Kologlu et al ., ). Co‐culture of Leydig cells with mouse spermatogonial stem cells (SSCs) and subsequent blockade of IIR signalling led to loss of expression of pluripotent genes in SSCs, supporting the idea that IGF1 produced by Leydig cells can maintain SSC pluripotency (Huang et al ., ).…”

Section: Role Of Igf System In Testicular Function: Lessons Learned Fmentioning

confidence: 97%

IGF signalling in germ cells and testicular germ cell tumours: roles and therapeutic approaches

Selfe

Shipley

2019

Andrology

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The insulin‐like growth factor (IGF) axis plays key roles in normal tissue growth and development as well as in the progression of several tumour types and their subsequent growth and progression to a metastatic phenotype. This review explores the role of IGF system in normal germ cell development and function in addition to examining the evidence for deregulation of IGF signalling in cancer, with particular relevance to evidence supporting a role in testicular germ cell tumours (TGCTs). Despite the clear preclinical rationale for targeting the IGF axis in cancer, there has been a lack of progress in identifying which patients may benefit from such therapy. Future employment of agents targeting the IGF pathway is expected to concentrate on their use in combination with other treatments to prevent resistance and exploit their potential as chemo‐ and radiosensitizers.

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“…Ovesen et al demonstrated an increase in sperm motility in GH-treated men and an increase in semen volume in oligospermic men treated with GH (78). In addition, it was found that GH supplementation caused an increase in germ cell number and an improvement in sperm morphology (82, 88). The potential mechanism by which GH may improve spermatogenesis is possibly through the stimulation of Leydig and Sertoli cell differentiation (14).…”

Section: Role Of Gh In Testesmentioning

confidence: 99%

Growth Hormone and Insulin-Like Growth Factor Action in Reproductive Tissues

et al. 2019

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The role of growth hormone (GH) in human fertility is widely debated with some studies demonstrating improvements in oocyte yield, enhanced embryo quality, and in some cases increased live births with concomitant decreases in miscarriage rates. However, the basic biological mechanisms leading to these clinical differences are not well-understood. GH and the closely-related insulin-like growth factor (IGF) promote body growth and development via action on key metabolic organs including the liver, skeletal muscle, and bone. In addition, their expression and that of their complementary receptors have also been detected in various reproductive tissues including the oocyte, granulosa, and testicular cells. Therefore, the GH/IGF axis may directly regulate female and male gamete development, their quality, and ultimately competence for implantation. The ability of GH and IGF to modulate key signal transduction pathways such as the MAP kinase/ERK, Jak/STAT, and the PI3K/Akt pathway along with the subsequent effects on cell division and steroidogenesis indicates that these growth factors are centrally located to alter cell fate during proliferation and survival. In this review, we will explore the function of GH and IGF in regulating normal ovarian and testicular physiology, while also investigating the effects on cell signal transduction pathways with subsequent changes in cell proliferation and steroidogenesis. The aim is to clarify the role of GH in human fertility from a molecular and biochemical point of view.

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Effects of Local and Sustained Release of FGF, IGF, and GH on Germ Cells in Unilateral Undescended Testis in Rats

Cited by 15 publications

References 31 publications

IGF1R signalling in testicular germ cell tumour cells impacts on cell survival and acquired cisplatin resistance

IGF1R signalling in testicular germ cell tumour cells impacts on cell survival and acquired cisplatin resistance

IGF signalling in germ cells and testicular germ cell tumours: roles and therapeutic approaches

Growth Hormone and Insulin-Like Growth Factor Action in Reproductive Tissues

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