Endocrinology, lecture on Calcium and Phosphage Balance
XXV. Calcium and Phosphate Homeostasis
A. Hormones involved are: Calcitonin, Parathormone, & Vitamin D
1. organs involved in regulation of homeostasis are:
bone, kidney, & gastrointestinal tract
a. but Ca++ participates in the function of most,
if not all, cells
i. myocontraction, nerve transmission, coagulation of blood
or milk, activation or inhibition of enzymes, hormone
function, exocytosis, cell-cell interaction, cell
duplication, and 2nd messenger function
B. Parathormone or Parathyroid hormone (PTH)
1. 84 aa (1-34 necessary for full potency; preproPTH = 115 aa)
a. homologous PTHrP (PTH-related protein) found in
mammary, bladder & uterus
2. secreted by the chief cells of the parathyroid glands
a. parathyroids embedded within the thyroid glands
i. oxyphil cells have no known function (appear after puberty)
b. low plasma Ca++ levels stimulates synthesis
and release of PTH via exocytosis
i. ususally high [Ca++] stimulates exocytosis
in endocrine or exocrine glands
3. PTH elevates plasma Ca++ levels
a. dissolving bone salts
i. activates osteoclasts in bone
(1) induces lysosomal enzymes
b. preventing renal excretion
i. stimulates Ca++ reabsorption
ii. promotes PO4 and bicarbonate excretion
4. 2nd messengers are cAMP and IP3 /PLC/ PKC
a. may act directly on osteoblasts (where receptors are found)
and indirectly activate osteoclasts
C. Calcitonin (Ct)
1. 32 aa peptide (136 aa prepro) made in parafollicular or C cells
in the thyroid gland
a. between or partially embeded in thyroid follicles
b. brain makes CGRP (calcitonin gene related peptide)
from the same precursor
c. high [Ca++] stimulates synthesis and secretion
2. Ct is a PTH antagonist
a. both work on the osteoclast
i. calcitonin directly; receptors on osteoclasts
ii. inhibits bone resorption, \ protects bone mass
b. promotes PO4 transport into cells; \ ¯ plasma levels
3. also works through cAMP and IP3/ PLC/ PKC
a. does not directly inhibit PTH action
b. results in a decrease in intracellular Ca++
D. Vitamin D (1,25-DHCC = 1,25-dihydroxycholecalciferol or cholecalciferol) and calcitriol
1. made from 7-dehydrocholesterol (or ergosterol from plants)
a. some must be absorbed from diet
b. UV aromatizes at skin, hydroxylated in the liver
i. Vitamin D is the prohormone
c. calcitriol is the active steroid
ii. hydroxylated from Vitamin D at kidney
2. calcitriol makes Ca++ absorption
in the digestive tract possible
a. induces a Ca++-binding peptide (CaBP)
i. a member of the calmodulin family
ii. PTH may also stimulate CaBP
b. diet is the main source of Ca++
i. PTH may stimulate calcitriol in intestines
c. promotes absorption of PO4 also
3. mimics and synergizes with PTH in bone
4. stimulates Ca++ reabsorption from the
distal convoluted tubule of the kidney
E. Other hormones
1. thyroid hormones ñ plasma Ca++, accelerate
replenishment of cellular Ca++
a. but inhibit intestinal absorption of Ca++
2. glucocorticoids reduce osteoblastic function and slow growth
a. may lead to osteoporosis
b. reduce intestinal absorption of Ca++
3. estrogens reduce the response of bone tissue to PTH
a. directly stimulate osteoblasts
b. potent inhibitor of osteoporosis
4. PRL, GH, & estrogens stimulate the production of calcitriol
