The role of the calcium-sensing receptor in the regulation of parathyroid hormone secretion in physiology and in calcitropic diseases

D. A. Marmalyuk; G. E. Runova; V. V. Fadeyev

doi:10.14341/osteo13142

The role of the calcium-sensing receptor in the regulation of parathyroid hormone secretion in physiology and in calcitropic diseases

D. A. Marmalyuk, G. E. Runova, V. V. Fadeyev

https://doi.org/10.14341/osteo13142

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Abstract

Parathyroid hormone (PTH) plays a key role in the regulation of calcium-phosphate metabolism. The secretion of PTH is regulated by calcium-sensing receptor (CaSR), which primarily expressed in the parathyroid glands and the renal tubules of the kidney. Increase of calcium concentration in extracellular matrix of cells is causing activation of the CaSR. Activated CaSR inhibits secretion of PTH and increases urinary calcium excretion. All CaSR effects leads to prevent development of hypercalcemia complications. Downregulation of the CASR expression and/or altered CaSR functioning leads to dysregulation of PTH synthesis. It may be the underlying cause of the development of primary and secondary hyperparathyroidism, as well as a number of hereditary diseases associated with loss- and gain-of-function mutations of the CaSR. In this paper we discusses the function of the CaSR in physiology and also the potential mechanisms that can impaired CaSR-induced signaling in various calcitropic diseases.

Keywords

calcium-sensing receptor, parathyroid hormone, primary hyperparathyroidism, secondary hyperparathyroidism, fibroblast growth factor 23, Klotho

About the Authors

D. A. Marmalyuk

I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Darya A. Marmalyuk - resident.

8–2 Trubetskaya street, 119991 Moscow

Competing Interests:

None

G. E. Runova

I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Gyuzel E. Runova - MD, PhD.

Moscow

Competing Interests:

None

V. V. Fadeyev

I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Valentin V. Fadeyev - MD, ScD, Professor.

Moscow

Competing Interests:

None

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Supplementary files

	1. Рисунок 1. Схематическое строение кальций-чувствительного рецептора.
	Subject
	Type	Материалы исследования
	View (232KB)	Indexing metadata ▾

	2. Рисунок 2. Сигнальные пути, опосредованные активацией кальций-чувствительного рецептора, в клетках околощитовидных желез.
	Subject
	Type	Материалы исследования
	View (174KB)	Indexing metadata ▾

	Title	Рисунок 2. Сигнальные пути, опосредованные активацией кальций-чувствительного рецептора, в клетках околощитовидных желез.
	Type	Материалы исследования
Brief description	CaSR – кальций-чувствительный рецептор; Ca²⁺ - ионы кальция; RGS5 - регулятор передачи сигналов G-белка 5; G_11/_q – семейство G-белков; ФоС – фосфолипаза С; ФИФ2 – фосфатидилинозитоладифосфат; ИФ3 – инозитолтрифосфат; ДАГ – диацилглицерол; РКС – протеинкиназа С; ФРФ23 – фактор роста фибробластов 23; MAPK/ERK – один из видов сигнального пути МАРК; FGFR – рецептор к ФРФ23; RCAN1 - регулятор кальциневрина 1; ПТГ – паратиреоидный гормон. Функционирование КЧР связано с активацией белка-G_q_/11, который регулирует дальнейшую работу вторичных посредников, таких как ИФ3 и ДАГ. Действие ИФ3 направлено на увеличение внутриклеточной концентрации кальция, которая подавляет секрецию ПТГ. ДАГ совместно с растущей концентрацией ионов кальция в цитозоле клетки регулирует пролиферацию клеток ОЩЖ через сигнальный путь МАРК/ERK.
	Date	2023-10-24
Language	ru
Digital Object Identifier	https://doi.org/10.14341/osteo13142-6010

	3. Рисунок 3. Расположение и функционирование кальций-чувствительного рецептора в а) восходящей толстой части петли Генле; б) в проксимальных канальцах почки.
	Subject
	Type	Материалы исследования
	View (196KB)	Indexing metadata ▾

	Title	Рисунок 3. Расположение и функционирование кальций-чувствительного рецептора в а) восходящей толстой части петли Генле; б) в проксимальных канальцах почки.
	Type	Материалы исследования
Brief description	CaSR – кальций-чувствительный рецептор; Ca²⁺ - ионы кальция; G_11/_q – представитель семейства G-белков; ПТГ – паратиреоидный гормон; PTH1R – рецептор к ПТГ 1 типа; G_s– представитель семейства G-белков; Na – ионы натрия; HPO₄ - фосфаты; NPT2 - натрий-зависимый фосфатный переносчик 2 типа; ФРФ23 – фактор роста фибробластов 23; FGFR – рецептор к ФРФ23. а) Гиперкальциемия активирует КЧР, который путем увеличения экспрессии клаудина-14, снижает реабсорбцию кальция а петле Генле. б) В проксимальных канальцах почки КЧР расположен на люменальной поверхности клетки. При повышении концентрации кальция в просвете канальца происходит активация КЧР, которая подавляет ингибирующий эффект ПТГ и ФРФ23 на натрий-зависимый фосфатный переносчик 2 типа (NPT2). Тем самым, возбуждение КЧР увеличивает абсорбцию фосфора из мочи.
	Date	2023-10-24
Language	ru
Digital Object Identifier	https://doi.org/10.14341/osteo13142-6012

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For citations:

Marmalyuk D.A., Runova G.E., Fadeyev V.V. The role of the calcium-sensing receptor in the regulation of parathyroid hormone secretion in physiology and in calcitropic diseases. Osteoporosis and Bone Diseases. 2023;26(3):25-32. (In Russ.) https://doi.org/10.14341/osteo13142

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	Title	Рисунок 1. Схематическое строение кальций-чувствительного рецептора.
	Type	Материалы исследования
	Date	2023-10-24
Digital Object Identifier	https://doi.org/10.14341/osteo13142-6009

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Osteoporosis and Bone Diseases

The role of the calcium-sensing receptor in the regulation of parathyroid hormone secretion in physiology and in calcitropic diseases

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