1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Molecular crosstalk between insulin‐like growth factors and follicle‐stimulating hormone in the regulation of granulosa cell function

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          The last phase of folliculogenesis is driven by follicle‐stimulating hormone (FSH) and locally produced insulin‐like growth factors (IGFs), both essential for forming preovulatory follicles.

          Methods

          This review discusses the molecular crosstalk of the FSH and IGF signaling pathways in regulating follicular granulosa cells (GCs) during the antral‐to‐preovulatory phase.

          Main findings

          IGFs were considered co‐gonadotropins since they amplify FSH actions in GCs. However, this view is not compatible with data showing that FSH requires IGFs to stimulate GCs, that FSH renders GCs sensitive to IGFs, and that FSH signaling interacts with factors downstream of AKT to stimulate GCs. New evidence suggests that FSH and IGF signaling pathways intersect at several levels to regulate gene expression and GC function.

          Conclusion

          FSH and locally produced IGFs form a positive feedback loop essential for preovulatory follicle formation in all species. Understanding the mechanisms by which FSH and IGFs interact to control GC function will help design new interventions to optimize follicle maturation, perfect treatment of ovulatory defects, improve in vitro fertilization, and develop new contraceptive approaches.

          Abstract

          Crosstalk between insulin‐like growth factors and follicle‐stimulating hormone in the regulation of ovarian antral follicles.

          Related collections

          Most cited references245

          • Record: found
          • Abstract: found
          • Article: not found

          AKT/PKB signaling: navigating downstream.

          The serine/threonine kinase Akt, also known as protein kinase B (PKB), is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Aberrant loss or gain of Akt activation underlies the pathophysiological properties of a variety of complex diseases, including type-2 diabetes and cancer. Here, we review the molecular properties of Akt and the approaches used to characterize its true cellular targets. In addition, we discuss those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Akt signalling in health and disease.

            Akt (also known as protein kinase B or PKB) comprises three closely related isoforms Akt1, Akt2 and Akt3 (or PKBα/β/γ respectively). We have a very good understanding of the mechanisms by which Akt isoforms are activated by growth factors and other extracellular stimuli as well as by oncogenic mutations in key upstream regulatory proteins including Ras, PI3-kinase subunits and PTEN. There are also an ever increasing number of Akt substrates being identified that play a role in the regulation of the diverse array of biological effects of activated Akt; this includes the regulation of cell proliferation, survival and metabolism. Dysregulation of Akt leads to diseases of major unmet medical need such as cancer, diabetes, cardiovascular and neurological diseases. As a result there has been substantial investment in the development of small molecular Akt inhibitors that act competitively with ATP or phospholipid binding, or allosterically. In this review we will briefly discuss our current understanding of how Akt isoforms are regulated, the substrate proteins they phosphorylate and how this integrates with the role of Akt in disease. We will furthermore discuss the types of Akt inhibitors that have been developed and are in clinical trials for human cancer, as well as speculate on potential on-target toxicities, such as disturbances of heart and vascular function, metabolism, memory and mood, which should be monitored very carefully during clinical trial. Copyright © 2011 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r).

              Newborn mice homozygous for a targeted disruption of insulin-like growth factor gene (Igf-1) exhibit a growth deficiency similar in severity to that previously observed in viable Igf-2 null mutants (60% of normal birthweight). Depending on genetic background, some of the Igf-1(-/-) dwarfs die shortly after birth, while others survive and reach adulthood. In contrast, null mutants for the Igf1r gene die invariably at birth of respiratory failure and exhibit a more severe growth deficiency (45% normal size). In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous system and epidermis. Igf-1(-/-)/Igf1r(-/-) double mutants did not differ in phenotype from Igf1r(-/-) single mutants, while in Igf-2(-)/Igf1r(-/-) and Igf-1(-/-)/Igf-2(-) double mutants, which are phenotypically identical, the dwarfism was further exacerbated (30% normal size). The roles of the IGFs in mouse embryonic development, as revealed from the phenotypic differences between these mutants, are discussed.
                Bookmark

                Author and article information

                Contributors
                costocco@uic.edu
                Journal
                Reprod Med Biol
                Reprod Med Biol
                10.1111/(ISSN)1447-0578
                RMB2
                Reproductive Medicine and Biology
                John Wiley and Sons Inc. (Hoboken )
                1445-5781
                1447-0578
                03 April 2024
                Jan-Dec 2024
                : 23
                : 1 ( doiID: 10.1111/rmb2.v23.1 )
                : e12575
                Affiliations
                [ 1 ] Department of Physiology and Biophysics University of Illinois Chicago College of Medicine Chicago Illinois USA
                [ 2 ] Department of Obstetrics and Gynecology University of Illinois Chicago College of Medicine Chicago Illinois USA
                Author notes
                [*] [* ] Correspondence

                Carlos Stocco, Department of Physiology and Biophysics, University of Illinois Chicago College of Medicine, Chicago, Illinois, USA.

                Email: costocco@ 123456uic.edu

                Author information
                https://orcid.org/0000-0001-7961-6681
                Article
                RMB212575 RMB-2024-0034.R1
                10.1002/rmb2.12575
                10988955
                38571513
                add6afcc-b57f-4b22-8e7d-b55183ced197
                © 2024 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 11 March 2024
                : 19 February 2024
                : 20 March 2024
                Page count
                Figures: 7, Tables: 0, Pages: 19, Words: 15056
                Funding
                Funded by: National Institutes of Health ‐ NIH
                Award ID: R01HD097202
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                January/December 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.0 mode:remove_FC converted:03.04.2024

                fsh,granulosa cells,insulin‐like growth factors,ovary,steroidogenesis

                Comments

                Comment on this article