Pth-KO Mouse

Parathyroid hormone (PTH) is a secreted peptide belonging to the PTH family. It plays a crucial role in bone mineral homeostasis, regulating calcium and phosphate levels in the body. PTH acts on bone and kidneys directly, and indirectly on the intestine to maintain calcium balance. It also has effects on energy metabolism, adipocytes, and is involved in non-classical functions [2,3,4]. PTH mediates its actions through PTH receptors (PTHRs), which are transmembrane G protein-coupled receptors [2].

The PTH gene mutations can cause isolated hypoparathyroidism. These mutations can lead to hypoparathyroidism through impaired PTH synthesis, induction of parathyroid cell apoptosis, or secretion of bioinactive PTH molecules [5]. TransCon PTH, a sustained-release prodrug designed to release PTH(1-34), was evaluated in a phase 1 trial. It was well-tolerated, and could provide physiological levels of PTH for the treatment of hypoparathyroidism [1].

In conclusion, PTH is essential for maintaining calcium and bone homeostasis, and also influences energy metabolism. The study of PTH gene mutations and the development of PTH-based therapies, like TransCon PTH, contribute to understanding and treating diseases related to PTH deficiency, such as hypoparathyroidism.

References:

1. Karpf, David B, Pihl, Susanne, Mourya, Sanchita, Markova, Denka, Leff, Jonathan A. 2020. A Randomized Double-Blind Placebo-Controlled First-In-Human Phase 1 Trial of TransCon PTH in Healthy Adults. In Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 35, 1430-1440. doi:10.1002/jbmr.4016. https://pubmed.ncbi.nlm.nih.gov/32212275/

2. Suarez-Bregua, Paula, Cal, Laura, Cañestro, Cristian, Rotllant, Josep. 2017. PTH Reloaded: A New Evolutionary Perspective. In Frontiers in physiology, 8, 776. doi:10.3389/fphys.2017.00776. https://pubmed.ncbi.nlm.nih.gov/29062283/

3. Tay Donovan, Yu Kwang, Bilezikian, John P. . Interactions between PTH and adiposity: appetizing possibilities. In Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 39, 536-543. doi:10.1093/jbmr/zjae056. https://pubmed.ncbi.nlm.nih.gov/38637302/

4. Rendina-Ruedy, Elizabeth, Rosen, Clifford J. 2022. Parathyroid hormone (PTH) regulation of metabolic homeostasis: An old dog teaches us new tricks. In Molecular metabolism, 60, 101480. doi:10.1016/j.molmet.2022.101480. https://pubmed.ncbi.nlm.nih.gov/35338013/

5. Hawkes, Colin P, Al Jubeh, Jamal M, Li, Dong, Rajiyah, Tara, Levine, Michael A. . Novel PTH Gene Mutations Causing Isolated Hypoparathyroidism. In The Journal of clinical endocrinology and metabolism, 107, e2449-e2458. doi:10.1210/clinem/dgac086. https://pubmed.ncbi.nlm.nih.gov/35165722/