Parathyroid hormone synthesis

H)D3 has been shown to suppress parathyroid hormone synthesis by parathyroid cells (Ritter et al. 2006 Ritter and Brown 2011). Lou et al. (2004) suggested that the metabolite at a high but physiological concentratiou acts as an active hormone... 

The a ns wer is a. (Hardman, pp 1525-1528.) Pa r a thyroid ho r m o ne is synthesized by and released from the parathyroid gland increased synthesis of PTI1 is a response to low serum Ca concentrations. Resorption and mobilization of Ca and phosphate from bone are increased in response to elevated PTI1 concentrations. Replacement of body stores of Ca is enhanced by the capacity of PTH to promote increased absorption of Ca by the small intestine in concert with vitamin D, which is the primary factor that enhances intestinal Ca absorption. Parathyroid hormone also causes an increased renal tubular reabsorption of Ca and excretion of phosphate. As a consequence of these effects, the extracellular Ca concentration becomes elevated. 

JP Tam, Q Yu. Methionine ligation strategy in the biomimetic synthesis of parathyroid hormones. Biopolymers 46, 319, 1998. 

T Kimura, M Takai, Y Masui, T Morika, S Sakakibara. Strategy for the synthesis of large peptides an application to the total synthesis of human parathyroid hormone [hPTH (1-84)]. Biopolymers 20, 1823, 1981. 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Parathyroid hormone is a single-chain polypeptide of 84 amino acids which is produced in the parathyroid glands. It increases serum calcium and decreases serum phosphate. In bone it promotes resorption of calcium. It indirectly increases osteoclastic activity by promoting the action of osteoblasts. It has been shown that in low doses PTH may even increase bone formation without stimulating bone resorption. In the kidney PTH increases resorption of calcium and it increases excretion of phosphate. An other important activity in the kidney is the enhanced synthesis of 1,25-dihydroxyvitamin D. An increased serum calcium level inhibits PTH secretion and increased serum phosphate decreases free serum calcium and thus stimulates PTH secretion. 

Renal osteodystrophy is a complex disorder with several pathogenic factors. Histological evidence of bone disease is common in early renal failure and deficits in calcitriol synthesis seems to be an important factor in the pathogenesis of secondary hyperparathyroidism in early CRF. The most common component is osteitis fibrosa manifested as subperiosteal resorption of bone. This is due to decreased excretion as well as increased secretion of parathyroid hormone. In CRF small increments of serum phosphorus cause small decreases in serum calcium. 

Mecfianism of Action Afat-soluble vitamin that is essential for absorption, utilization of calcium phosphafe, and normal calcification of bone. Therapeutic Effect Stimulates calcium and phosphate absorption from small inf esf ine, promof es secretion of calcium from bone fo blood, promofes renal tubule phosphate resorption, acts on bone cells to stimulate skeletal growth and on parathyroid gland to suppress hormone synthesis and secretion. 

Mechanism of Action An antibiotic that forms complexes with DNA, inhibiting DNA-directed RNA synthesis. May inhibit parathyroid hormone effect on osteoclasts and inhibit bone resorption. TherapeuticEffect Lowers serum calcium and phosphate levels. Blocks hypercalcemic action of vitamin Dand action of parathyroid hormone. Decreases serum calcium. 

Vitamin D is obtained in the diet or by photolysis of 7-dehydrocholesterol in skin exposed to sunlight. Calcitriol works in concert with parathyroid hormone in Ca2+ homeostasis, regulating [Ca2+] in the blood and the balance between Ca2+ deposition and Ca2+ mobilization from bone. Acting through nuclear receptors, calcitriol activates the synthesis of an intestinal Ca2+-binding protein essential for uptake of dietary Ca2+. Inadequate dietary vitamin D or defects in the biosynthesis of calcitriol result in serious diseases such as rickets, in which bones are weak and malformed (see Fig. 10-20b). 

Hormone synthesis and release can be initiated by both extrinsic and intrinsic factors.2 Extrinsic factors include various environmental stimuli such as pain, temperature, light, and smell. Intrinsic stimuli include various humoral and neural factors. For instance, release of a hormone can be initiated by other hormones. These occurrences are particularly typical of the anterior pituitary hormones, which are controlled by releasing hormones from the hypothalamus. Hormonal release can be influenced by neural input a primary example is the sympathetic neural control of epinephrine and norepinephrine release from the adrenal medulla. Other intrinsic factors that affect hormone release are the levels of ions and metabolites within the body. For instance, parathyroid hormone release is governed directly by the calcium concentration in the bloodstream, and the release of... 

Yi H, Fukagawa M, Yamamoto H et al. (1995) Prevention of enhanced parathyroid hormone secretion, synthesis and hyperplasia by mild dietary phosphorus restriction in early chronic renal failure in rats. Possible direct role of phosphorus. Nephron 70 242-248... 

The active metabolite of vitamin D, calcitriol, is formed in the proximal tubules of the kidneys from calcidiol. There are three cytochrome P450-dependent enzymes in kidneys that catalyze 1-hydroxylation of calcidiol CYP27A and CYP27 in mitochondria and a microsomal la-hydroxylase, which is ferredoxin-dependent. It is likely that the microsomal enzyme is the most important its synthesis is induced by cAMP in response to parathyroid hormone (Section 3.2.8.2) and repressed by calcitriol (Omdahl et al., 2001 Wikvall, 2001). 

There is evidence that 24-hydroxycalcidiol has physiological functions distinct from those of calcitriol, and the regulation of the 24-hydroxylase suggests that it functions to provide a metabolically active product, as well as diverting calcidiol away from calcitriol synthesis (Henry, 2001). Studies of knockout mice lacking the 24-hydroxylase show that 24-hydroxycalcidiol has a role in both in-tramembranous bone formation during development and the suppression of parathyroid hormone secretion (St-Arnaud, 1999 van Leeuwen et al., 2001). 

In the kidneys, parathyroid hormone increases 1 -hydroxylation of calcidiol and reduces 24-hydroxylation. This is not the result of de novo enzyme synthesis, but an effect on the activity of the preformed enzymes, mediated by cAMP-dependent protein kinases. In turn, calcitriol has a direct role in the control of parathyroid hormone, acting to repress expression of the gene. In chronic renal failure, there is reduced synthesis of calcitriol, leading to the development of secondary hyperparathyroidism that results in excess mobilization of bone mineral, hypercalcemia, hypercalciuria, hyperphosphaturia, and the development of calcium phosphate renal stones. 

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