Ca++ isbound(i.e.,complexed)tovariousanionsinplasma,includingHCO3− ,citrate,andSO42− .Piiscomplexedtovariouscations,includingNa+ andK+ .FromKoeppenBM,StantonBA.Renal Physiology. 4thed.Philadelphia:Mosby;2007.
Physiological Regulation of Calcium and Phosphate: Parathyroid Hormone and 1,25-Dihydroxyvitamin D C
PTH and 1,25-dihydroxyvitamin D are the two physiologically most important hormones dedicated to mainte- nance of normal blood Ca and Pi in humans. As such they are referred to as calciotropic hormones. The structure, synthesis, and secretion of these two hormones and their receptors will be discussed first. In the following section, the detailed actions of PTH and 1,25-dihydroxyvitamin D on the three key sites of Ca/Pi homeostasis (i.e., gut, bone, and kidney) are discussed.
The predominant parenchymal cell type in the parathyroid B gland is the principal (also called chief) cell (
Fig. 40.2
PTH is the primary hormone that protects against hypocalcemia. The primary targets of PTH are bone and the kidneys. PTH also functions in a positive feed-forward loop by stimulating production of 1,25-dihydroxyvitamin D.
•Fig. 40.2 AandB,Histologyofparathyroidglands.A,adiposetissuewithinparathyroidglands;C,capillaries;O,oxyphilcells;P,principalorchiefcells.(FromYoungBetal.Wheater’s Functional Histology. 5thed.Philadelphia:ChurchillLivingstone;2006.)
Structure, Synthesis, and Secretion
PTH is secreted as an 84–amino acid polypeptide and is synthesized as a prepro-PTH, which is proteolytically processed to pro-PTH in the endoplasmic reticulum and then to PTH in the Golgi and secretory vesicles. PTH has a short half-life in the circulation (2 minutes), consistent with its role in minute-to-minute regulation of plasma calcium.
Because the PTH receptor also binds PTH-related peptide (PTHrP), it is usually referred to as the PTH/PTHrP receptor. The PTH/PTHrP receptor is expressed on osteoblasts in bone and in the proximal and distal tubules of the kidney, and it is the receptor that mediates the systemic actions of PTH. However, the PTH/PTHrP receptor is also expressed in many developing organs in which PTHrP has important paracrine functions. One such example is regulation of chondrocyte proliferation in the growth plate during endochondral bone growth.
Vitamin D is a prohormone that must undergo two successive hydroxylation reactions to become the active form known as 1,25-dihydroxyvitamin D or calcitriol (
Fig.
40.5 ). This hormone plays a critical role in Ca absorption
Extracellular[Ca++]issensedbytheparathyroidchiefcellthroughaplasmamembranecalcium-sensing receptor (CaSR). TheprimarysignalthatstimulatesPTHsecretionisadecreaseincirculating[Ca++](