Effects of the insulin‐like growth factor system on testicular differentiation and function: a review of the literature

Cannarella, Rossella; Condorelli, Rosita A.; Vignera, Sandro La; Calogero, Aldo E.

doi:10.1111/andr.12444

Cited by 70 publications

(64 citation statements)

References 61 publications

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“…However, number of pups per litter in SC-α1AMPK-cKO mice did decrease by 25%, accompanied with disturbed cell junction dynamics 86 . Thus, for the purpose of elucidating the molecular basis and developing therapeutic options for azoospermia therapy, the causes of azoospermia deserve more attention in the future, especially from the perspective of the TGF-β/Smad, AMPK, and MAPK signaling pathways in SCs [147][148][149][150] .…”

Section: Pathways and Potential Clinical Applications Of Abnormal Spementioning

confidence: 99%

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

2019

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The functions of Sertoli cells in spermatogenesis have attracted much more attention recently. Normal spermatogenesis depends on Sertoli cells, mainly due to their influence on nutrient supply, maintenance of cell junctions, and support for germ cells’ mitosis and meiosis. Accumulating evidence in the past decade has highlighted the dominant functions of the MAPK, AMPK, and TGF-β/Smad signaling pathways during spermatogenesis. Among these pathways, the MAPK signaling pathway regulates dynamics of tight junctions and adherens junctions, proliferation and meiosis of germ cells, proliferation and lactate production of Sertoli cells; the AMPK and the TGF-β/Smad signaling pathways both affect dynamics of tight junctions and adherens junctions, as well as the proliferation of Sertoli cells. The AMPK signaling pathway also regulates lactate supply. These signaling pathways combine to form a complex regulatory network for spermatogenesis. In testicular tumors or infertile patients, the activities of these signaling pathways in Sertoli cells are abnormal. Clarifying the mechanisms of signaling pathways in Sertoli cells on spermatogenesis provides new insights into the physiological functions of Sertoli cells in male reproduction, and also serves as a pre-requisite to identify potential therapeutic targets in abnormal spermatogenesis including testicular tumor and male infertility.

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Section: Pathways and Potential Clinical Applications Of Abnormal Spementioning

confidence: 99%

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

2019

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“…Nonetheless, appropriate models remain to be developed to directly test how IGF1 directly and independently mediates adrenal cortical and Leydig cell function in adults, and how these actions would ultimately influence metabolic function. It should be noted that IGF1 may also support male fertility via regulation of Sertoli cell development (Cannarella et al 2018); however, Sertolispecific manipulation of IGF1/IGF1R remains to be explored.…”

Section: Journal Of Molecular Endocrinologymentioning

confidence: 99%

40 YEARS of IGF1: Understanding the tissue-specific roles of IGF1/IGF1R in regulating metabolism using the Cre/loxP system

Kineman

Río-Moreno

Sarmento‐Cabral

2018

Journal of Molecular Endocrinology

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It is clear that insulin-like growth factor-1 (IGF1) is important in supporting growth and regulating metabolism. The IGF1 found in the circulation is primarily produced by the liver hepatocytes, but healthy mature hepatocytes do not express appreciable levels of the IGF1 receptor (IGF1R). Therefore, the metabolic actions of IGF1 are thought to be mediated via extra-hepatocyte actions. Given the structural and functional homology between IGF1/IGF1R and insulin receptor (INSR) signaling, and the fact that IGF1, IGF1R and INSR are expressed in most tissues of the body, it is difficult to separate out the tissue-specific contributions of IGF1/IGF1R in maintaining whole body metabolic function. To circumvent this problem, over the last 20 years, investigators have taken advantage of the Cre/loxP system to manipulate IGF1/IGF1R in a tissue-dependent, and more recently, an age-dependent fashion. These studies have revealed that IGF1/IGF1R can alter extra-hepatocyte function to regulate hormonal inputs to the liver and/or alter tissue-specific carbohydrate and lipid metabolism to alter nutrient flux to liver, where these actions are not mutually exclusive, but serve to integrate the function of all tissues to support the metabolic needs of the organism.

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“…A number of studies have assigned a role in SC function to the insulin-like growth factor 1 receptor (IGF1R), which belongs to the tyrosine kinases receptor family [3]. Accordingly, the IGF1R is expressed in SCs and is required for testis development [4] and SC proliferation [5].…”

Section: Introductionmentioning

confidence: 99%

The IGF1 Receptor Is Involved in Follicle-Stimulating Hormone Signaling in Porcine Neonatal Sertoli Cells

Cannarella

Arato

Condorelli

et al. 2019

JCM

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Experimental evidence has shown that the IGF1 receptor (IGF1R) is involved in testicular development during embryogenesis. More recently, data gathered from mice granulosa cells and zebrafish spermatogonia suggest that IGF1R has a role in Follicle-stimulating hormone (FSH) signaling. No evidence has been reported on this matter in Sertoli cells (SCs) so far. The aim of the study was to evaluate the role, if any, of the IGF1R in FSH signaling in SCs. The effects of FSH exposure on myosin-phosphatase 1 (MYPT1), ERK 1/2, AKT308, AKT473, c-Jun N-terminal kinase (JNK) phosphorylation and on anti-Müllerian hormone (AMH), inhibin B and FSH receptor (FSHR) mRNA levels were assessed with and without the IGF1R inhibitor NVP-AEW541 in purified and functional porcine neonatal SCs. Pre-treatment with NVP-AEW541 inhibited the FSH-induced MYPT1 and ERK 1/2 phosphorylation, decreased the FSH-dependent Protein kinase B (AKT)308 phosphorylation, but did not affect the FSH-induced AKT473 and JNK phosphorylation rate. It also interfered with the FSH-induced AMH and FSHR down-regulation. No influence was observed on the FSH-stimulated Inhibin B gene expression. Conclusion. These findings support the role of theIGF1R in FSH signaling in porcine SCs. The possible influence of IGF1 stimulation on the FSH-mediated effects on SCs should be further explored.

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Effects of the insulin‐like growth factor system on testicular differentiation and function: a review of the literature

Cited by 70 publications

References 61 publications

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

40 YEARS of IGF1: Understanding the tissue-specific roles of IGF1/IGF1R in regulating metabolism using the Cre/loxP system

The IGF1 Receptor Is Involved in Follicle-Stimulating Hormone Signaling in Porcine Neonatal Sertoli Cells

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