The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function
Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the <i>GH receptor</i> (<i>GHR</i>), which is the main factor influencing human development and is essential to...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/18/13908 |
| _version_ | 1797579741713137664 |
|---|---|
| author | Ghadeer Falah Lital Sharvit Gil Atzmon |
| author_facet | Ghadeer Falah Lital Sharvit Gil Atzmon |
| author_sort | Ghadeer Falah |
| collection | DOAJ |
| description | Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the <i>GH receptor</i> (<i>GHR</i>), which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR isoform, which lacks exon 3 has recently been related to longevity; individuals carrying this isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the wild type (WT) isoform (flGHR). Further, studies performed in patients with acromegaly, Prader–Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR isoform may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject. |
| first_indexed | 2024-03-10T22:40:31Z |
| format | Article |
| id | doaj.art-a2b014d210604b5ca353f4d480c22788 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:40:31Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a2b014d210604b5ca353f4d480c227882023-11-19T11:04:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181390810.3390/ijms241813908The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR FunctionGhadeer Falah0Lital Sharvit1Gil Atzmon2Faculty of Natural Sciences, University of Haifa, Haifa 3498838, IsraelFaculty of Natural Sciences, University of Haifa, Haifa 3498838, IsraelFaculty of Natural Sciences, University of Haifa, Haifa 3498838, IsraelGrowth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the <i>GH receptor</i> (<i>GHR</i>), which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR isoform, which lacks exon 3 has recently been related to longevity; individuals carrying this isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the wild type (WT) isoform (flGHR). Further, studies performed in patients with acromegaly, Prader–Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR isoform may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.https://www.mdpi.com/1422-0067/24/18/13908growth hormone receptorhuman growth hormonedeletion of exon 3polymorphismgrowth and developmenthormone deficiency |
| spellingShingle | Ghadeer Falah Lital Sharvit Gil Atzmon The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function International Journal of Molecular Sciences growth hormone receptor human growth hormone deletion of exon 3 polymorphism growth and development hormone deficiency |
| title | The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function |
| title_full | The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function |
| title_fullStr | The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function |
| title_full_unstemmed | The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function |
| title_short | The Exon 3-Deleted Growth Hormone Receptor (d3GHR) Polymorphism—A Favorable Backdoor Mechanism for the GHR Function |
| title_sort | exon 3 deleted growth hormone receptor d3ghr polymorphism a favorable backdoor mechanism for the ghr function |
| topic | growth hormone receptor human growth hormone deletion of exon 3 polymorphism growth and development hormone deficiency |
| url | https://www.mdpi.com/1422-0067/24/18/13908 |
| work_keys_str_mv | AT ghadeerfalah theexon3deletedgrowthhormonereceptord3ghrpolymorphismafavorablebackdoormechanismfortheghrfunction AT litalsharvit theexon3deletedgrowthhormonereceptord3ghrpolymorphismafavorablebackdoormechanismfortheghrfunction AT gilatzmon theexon3deletedgrowthhormonereceptord3ghrpolymorphismafavorablebackdoormechanismfortheghrfunction AT ghadeerfalah exon3deletedgrowthhormonereceptord3ghrpolymorphismafavorablebackdoormechanismfortheghrfunction AT litalsharvit exon3deletedgrowthhormonereceptord3ghrpolymorphismafavorablebackdoormechanismfortheghrfunction AT gilatzmon exon3deletedgrowthhormonereceptord3ghrpolymorphismafavorablebackdoormechanismfortheghrfunction |