Parathyroid Hormones and Related Peptides

Introduction

Parathyroid hormone (PTH) is a polypeptide molecule synthesized and secreted by parathyroid gland main cells, which consists of 84 amino acids. Parathyroid hormone-related protein (PTHrP) is a 139- to 173-amino-acid protein with N-terminal homology to PTH. PTHrP complex gene is expressed in different tissues. The primary amino acid sequences of both the PTH-like and non-PTH-like regions of the protein are highly conserved among species. Apart from the classical and non-classical PTH activity in the N-terminal region, other biological functions were also found. These include increasing calcium transport in the central region of PTHrP and a C-terminal peptide that effectively inhibits bone resorption. The NH₂-terminal region of PTHrP and the corresponding PTH domain are homologous, and the ability of these two molecules to interact with a co-receptor. This seems to explain the ability of PTHrP to mimic many of the effects of PTH on calcium and phosphorus homeostasis and bone turnover.

Mechanism of action

PTH mainly acts on the high level of parathyroid hormone I receptor in bone, kidney, central nervous system and pancreas. Blood calcium levels are mainly affected by the PTH II receptor in the testis and placenta. Regulation of calcium and phosphorus metabolism is accomplished by PTH via cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and vitamin D, which can maintain the health of mineralized tissue. PTHrP may stimulate multiple signals (cAMP, creatine phosphate and calcium) by activating a common receptor between bone and kidney. In smooth muscle cells, PTH and PTHrP reduce the effects of extracellular calcium through a cAMP-dependent mechanism. PTHrP regulates cardiovascular function mainly by binding to and activating PTH/PTHrP receptors, PTHrP I receptor is most closely related to vascular smooth muscle cell proliferation and vascular tone regulation.

Application of Parathyroid Hormones and Related Peptides

PTH is a polypeptide necessary to maintain calcium homeostasis and excess or deficiency can lead to serious disease. PTHrP is a cardiovascular regulatory peptide that plays an important role in cardiovascular system development, blood pressure regulation, and vascular calcification. Both PTH and PTHrP regulate calcium and phosphorus metabolism in vascular cells and osteoblasts and are major pathological regulators of calcium homeostasis.

References

1. Burtis, W. J. (1992). Parathyroid hormone-related protein: structure, function, and measurement. Clinical Chemistry, 38(11), 2171-2183.
2. Amizuka, N., Warshawsky, H., Henderson, J. E., Goltzman, D., Karaplis, A. C. (1994). Parathyroid hormone-related peptide (pthrp)-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation. Journal of Cell Biology, 126(6), 1611-1623.
3. Leder, B. Z., O'Dea, L. S. L., Zanchetta, J. R., Kumar, P., Banks, K., McKay, K., ... & Hattersley, G. (2015). Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. The Journal of Clinical Endocrinology & Metabolism, 100(2), 697-706.