GPHB5, also known as glycoprotein hormone beta 5, is a subunit of corticotroph-derived glycoprotein hormone (CGH), which is a non-covalent heterodimer with glycoprotein hormone alpha 2 (GPHA2). CGH can activate the TSH receptor. GPHB5 has been associated with metabolic-related pathways, such as lipolysis and neuroactive ligand-receptor interaction pathways, and is thought to play a role in glucose and lipid metabolism [1].

Animal studies have shown that transgenic overexpression of GPHB5 in mice leads to elevations in serum T4 levels, reductions in body weight, and proptosis [3]. In human studies, circulating GPHB5 levels are significantly increased in women with metabolic syndrome (MetS), insulin resistance (IR), and polycystic ovary syndrome (PCOS). These levels are positively correlated with factors like BMI, blood pressure, and lipid parameters, and negatively correlated with adiponectin. Treatments like GLP-1RA, metformin, and TZDs can decrease GPHB5 levels [1,2]. In addition, in triploid Atlantic salmon, Gphb5 is significantly down-regulated in fish with lower jaw deformity (LJD), suggesting a possible hormonal involvement in LJD [4].

In conclusion, GPHB5 is associated with metabolism-related functions and may serve as a biomarker for metabolic-related diseases such as MetS, IR, and PCOS in women. Its role in other conditions like LJD in fish also indicates a potential broader impact on skeletal physiology. Research on GPHB5, including through mouse models, has provided insights into its function in these biological processes and disease conditions.

References:

1. Xiang, Ting, Zhang, Siliang, Li, Qinge, Yang, Gangyi, Yang, Mengliu. 2022. GPHB5 Is a Biomarker in Women With Metabolic Syndrome: Results From Cross-Sectional and Intervention Studies. In Frontiers in endocrinology, 13, 893142. doi:10.3389/fendo.2022.893142. https://pubmed.ncbi.nlm.nih.gov/35757403/

2. Wang, Yanping, Xiang, Ting, Xia, Xuyun, Liang, Zerong, He, Jianguo. 2022. Elevated circulating GPHB5 levels in women with insulin resistance and polycystic ovary syndrome: A cross-sectional study and multiple intervention studies. In Frontiers in endocrinology, 13, 1010714. doi:10.3389/fendo.2022.1010714. https://pubmed.ncbi.nlm.nih.gov/36568071/

3. Okada, Shannon L, Ellsworth, Jeff L, Durnam, Diane M, Yao, Lena Y, Webster, Philippa J. 2005. A glycoprotein hormone expressed in corticotrophs exhibits unique binding properties on thyroid-stimulating hormone receptor. In Molecular endocrinology (Baltimore, Md.), 20, 414-25. doi:. https://pubmed.ncbi.nlm.nih.gov/16210345/

4. Amoroso, Gianluca, Ventura, Tomer, Cobcroft, Jennifer M, Elizur, Abigail, Carter, Chris G. 2016. Multigenic Delineation of Lower Jaw Deformity in Triploid Atlantic Salmon (Salmo salar L.). In PloS one, 11, e0168454. doi:10.1371/journal.pone.0168454. https://pubmed.ncbi.nlm.nih.gov/27977809/