Parathyroid hormone (PTH)
PTH is synthesized and released from chief cells in the parathyroid gland. PTH is transcribed in its pro form of 115 amino acids. First cleavage occurs on rough endoplasmic reticulum, where 25 amino acids long fragment is cleaved. Second cleavage occurs during processing, resulting in 84 amino acid long PTH. In this form PTH is secreted. However, this form is rapidly metabolised by the organism (mostly in the liver), resulting in 33- or 36-amino-acid N-terminal peptide and the remaining C-terminal peptide. It appears that only the former is biologically active while the C-terminal does not exert any function in the body. Parent PTH has also biological active, but it is not as potent as the N-terminus fragment.
Regulation of synthesis and secretion
Secretion and synthesis of PTH is stimulated by low Ca2+ blood plasma levels. When this happens, hormone is continuously released into bloodstream. To meet demands, new hormone is continuously produced. However, when calcium levels remain in a normal range, PTH is released into blood in an intermittent manner. Action of PTH depends upon mode of secretion.
Hormone secretion and synthesis is inhibited by ionized calcium in plasma and vitamin D. Vitamin D receptor (VDR) is a nuclear receptor. Upon binding of a lignad, VDR forms a heterodimer with retinoid acid X receptor. The complex acts as a transcriptional regulator on PTH gene. Complex binds to vitamin D response element causing decrease in PTH transcription.
Ionized calcium exerts its function on PTH secretion through Ca2+-sensing receptor (CaSR), which acts in a saturable manner. CaSR is a G-protein-coupled-receptor (GPCR) coupled to Gαq which activates PLC pathway. This results in inhibition of PTH secretion and synthesis.
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Either form of PTH acts on PTH 1R and PTH 2R receptors, but function of the later has not been identified so far. The former is most abundant in kidney and bone, where function of PTH is easily observed. Proximal and distal convoluted tubule in the kidney and osteoblasts in bone are targets for PTH. PTH 1R receptor is a GPCR coupled to Gαq and Gαs. Former activates PLC signalling pathway, while Gαs activates adenylyl cyclase pathway. These two signalling cascades activate different transcription modifying factors. In case of kidneys, Ca2+ reabsorption increases, phosphate reabsorption decreases and synthesis of 1,25-Dihydroxyvitamin D increases. In case of the bone, depending on mode of secretion, causes bone mineralization or bone resorption.
Calcitonin acts on calcitonin receptor, which is a GPCR, coupled to either Gαq or Gαs, depending on target cell localization. In bone, it activates adenylyl cyclase pathway in
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osteoclasts, which results in inhibition of bone resorption and slight shift of balance towards bone mineralization. This effect of
It has to be noted that calcitonin importance for human body is questionable. Elevated levels of
Particularly testosterone in males and estradiol in females are involved in regulating bone mass. In females, rapid decline in estradiol levels are parallel to increased probability of osteoporosis (described in Diseases section). Therefore, it is proposed that sex hormones promote calcium and phosphate deposition in bones.
Vitamin D can also be considered a hormone, however since its main source is diet, it is termed a vitamin.