Ghr, the growth hormone receptor, is a membrane-bound receptor belonging to the class I cytokine receptor superfamily [2]. When growth hormone (GH) binds to Ghr, it induces cell differentiation, maturation, anabolism, and proliferation [2]. The GH-Ghr-IGF1 axis is crucial for somatic growth, regulating processes like cell proliferation, differentiation, division, and survival [4]. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying Ghr's function.

In GHR-/-mice, removal of GH action leads to depot-specific changes in immune cell populations in white adipose tissue (WAT), protecting them from age-related WAT inflammation and immune cell infiltration despite obesity [5]. In a study on ARC-GHR neurons in transgenic mice, activation of these neurons regulated muscle glucose uptake, improving glucose tolerance and insulin sensitivity specifically in skeletal muscle [1]. Additionally, GHR knockdown in HCC cells enhanced their sensitivity to sorafenib, potentially through inhibiting the PI3K/AKT/ERK1/2 signaling pathway [3]. In gastric cancer, silencing GHR inhibited cell growth and promoted apoptosis via the PI3K/AKT signaling pathway, causing G1 cell cycle arrest [2].

In conclusion, Ghr is essential for growth-related processes, metabolism, and cell-cycle regulation. Model-based research, especially using Ghr KO mouse models, has revealed its role in diseases such as obesity-related inflammation, diabetes-related glucose metabolism, and cancer development. Understanding Ghr's function provides insights into potential therapeutic strategies for these disease areas.

References:

1. de Lima, Juliana Bezerra Medeiros, Debarba, Lucas Kniess, Rupp, Alan C, Sandoval, Darleen A, Sadagurski, Marianna. 2021. ARCGHR Neurons Regulate Muscle Glucose Uptake. In Cells, 10, . doi:10.3390/cells10051093. https://pubmed.ncbi.nlm.nih.gov/34063647/

2. Yan, Hong-Zhu, Wang, Hua-Feng, Yin, Yueling, He, Ying, He, Bo-Sheng. 2021. GHR is involved in gastric cell growth and apoptosis via PI3K/AKT signalling. In Journal of cellular and molecular medicine, 25, 2450-2458. doi:10.1111/jcmm.16160. https://pubmed.ncbi.nlm.nih.gov/33492754/

3. Gao, Shuang, Ni, Qianwen, Wu, Xiuli, Cao, Tieliu. 2020. GHR knockdown enhances the sensitivity of HCC cells to sorafenib. In Aging, 12, 18127-18136. doi:10.18632/aging.103625. https://pubmed.ncbi.nlm.nih.gov/32970612/

4. Hu, Bowen, Li, Hongmei, Zhang, Xiquan. 2021. A Balanced Act: The Effects of GH-GHR-IGF1 Axis on Mitochondrial Function. In Frontiers in cell and developmental biology, 9, 630248. doi:10.3389/fcell.2021.630248. https://pubmed.ncbi.nlm.nih.gov/33816476/

5. Young, Jonathan A, Henry, Brooke E, Benencia, Fabian, Kopchick, John J, Berryman, Darlene E. 2020. GHR-/- Mice are protected from obesity-related white adipose tissue inflammation. In Journal of neuroendocrinology, 32, e12854. doi:10.1111/jne.12854. https://pubmed.ncbi.nlm.nih.gov/32350959/