6-Ca%20homeostasis[1] - Bioregulation of Calcium and...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Bioregulation of Calcium and Phosphate Homeostasis I. Importance of Calcium and Phosphate 1 Role of calcium • Bone & tooth formation tooth formation • Muscle contraction • Release of secretory granules in neurons and glandular cells • Second messenger • Cofactor in blood clotting • High levels in mammalian milk & avian egg shells 2 Role of phosphate • Essential component of bones & teeth component of bones teeth • Many essential molecules contain phosphate: phospholipids in cell membrane, nucleic acids, nucleotides, etc. • Energy storage as ATP, creatine phosphate • Second messengers: cAMP, cGMP • Activation of many enzymes via protein kinases • Major buffer system in urine Interrelationship between Ca2+ and HPO42• Product of free plasma concentrations of of free plasma concentrations of 2+ and HPO 2- is constant for a given Ca 4 physiological state if [Ca2+] [HPO42-] and vice versa 3 Bone formation and resorption • Calcium phosphate is present as small phosphate is present as small crystals: hydroxyapatite crystals • Osteoblasts are responsible for bone formation • Osteocytes (derived from osteoblasts) are completely surrounded by bone completely surrounded by bone • Osteoclasts are responsible for bone resorption 4 II Endocrine Regulation of Calcium II. Endocrine Regulation of Calcium and and Phosphate Homeostasis in Mammals Hormones involved in Ca homeostasis • Parathyroid hormone (PTH) secreted by the hormone (PTH) secreted by the parathyroid glands • Calcitonin (CT) secreted by parafollicular cells = C-cells in the thyroid • 1,25-dihydroxycholecalciferol (1,25-DHC) = calcitriol = derivative of vitamin D3 secreted by the combined activities of skin, liver & kidney • PTH & CT signal via GPCRs, calcitriol signals via a nuclear vitD receptor 5 Parathyroid glands and PTH • Embedded within the thyroid glands in some within the thyroid glands in some mammals including man and dogs • Separate glands located near the thyroid in other mammals including rat • Glands arise from pharyngeal endoderm but chief cells that produce PTH have a neuroectodermal origin • PTH is a 84 AA polypeptide • Hypercalcemic, increases plasma [Ca2+] 6 Regulation of PTH secretion 7 C-cells and CT • C-cells or parafollicular cells (origin neural or parafollicular cells (origin neural crest cells in ultimobranchial bodies) lay between the thyroid follicles in the thyroid gland • CT is a 32 AA peptide • Hypocalcemic, reduces plasma [Ca2+] reduces plasma [Ca colloid in lumen thyroid gland gland follicular cell capillary parafollicular cell blood vessel nerve 8 1,251,25-DHC = calcitriol • Derivative of vitamin D3, produced by of vitamin produced by combined action of skin, liver and kidney • Vitamin D3 is produced in the skin or taken up from the intestine • Essential role in Ca2+ absorption = calcitriol 9 III. Interactions of PTH, CT, and 1,251,25-DHC 10 Ca2+ and HPO42- regulation in bone • Minute-to-minute regulation of plasma Ca2+ and regulation of plasma Ca 2- levels: HPO4 osteocytic osteolysis caused by PTH • Major changes (growth, pregnancy, lactation): interaction of PTH, calcitriol, and CT on osteoclasts and osteoblasts osteoclasts and osteoblasts • CT mainly inhibits osteoclasts, PTH stimulates both osteoblasts and osteoclasts (depending on dose) Regulation of Ca2+ uptake in intestine • Calcitriol stimulates synthesis of calcium-binding stimulates synthesis of calcium proteins such as calbindin • Calbindin facilitates uptake of Ca2+ at the mucosal surface of epithelial cells • It binds Ca2+ intracellularly during the transport to the serosal border (protection) • At the serosal border Ca2+ is transported into the interstitial fluid and then diffuses into the blood capillaries • HPO42- follows passively 11 Ca2+ and HPO42- regulation in kidney • PTH increases HPO42- excretion and hence Ca2+ increases HPO and hence Ca reabsorption • PTH stimulates production of calcitriol in the kidney 12 13 Rachitis = rickets Other Other hormones and Ca homeostasis • Thyroid hormones & glucocorticoids influence hormones glucocorticoids influence mineral homeostasis • GH has indirect effects via IGFs • Estrogens and androgens have important stimulatory effects on osteoblast activity increased risk of osteoporosis in menopause risk of osteoporosis in menopause and andropause 14 15 ...
View Full Document

This note was uploaded on 10/11/2011 for the course BIOLOGY G0G49A taught by Professor V.darras during the Fall '11 term at Katholieke Universiteit Leuven.

Ask a homework question - tutors are online