Genes polypeptide hormones

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Fig. 1.46. Alternative polyadenylation in the expression of calcitonin genes of rat. The primary transcript of the calcitonin gene possesses two polyadenylation sites. One site is nsed in the processing of RNA in the thyroid, another site in the brain, and yet another in nerve tissne. The translation of the two mRNAs creates two pre-hormones, from which two different polypeptide hormones (calcitonin and the calcitonin-related peptide", or CGRP) are created via proteolysis.

Pseudohypoparathyroidism is a heritable disorder caused by target organ unresponsiveness to parathyroid hormone (a polypeptide hormone secreted by the parathyroid gland). One of the mutations causing this disease occurs in the gene encoding Gstt in certain cells. 

Growth factors, cytokines, polypeptide hormones, and a number of other signal molecules regulate gene transcription through phosphorylation of specific transcription factors by receptor kinases. 

The gene for a eukaryotic polypeptide hormone was isolated, cloned, sequenced, and overexpressed in a bacterium. After the polypeptide was purified from the bacterium, it failed to function when it was subjected to a bioassay in the organism from which the gene was isolated. Speculate why the recombinant DNA product was inactive. 

Secretin a polypeptide hormone, M, 3,050, containing 27 amino acid residues. S. shows considerable sequence homology with Glucagon (see). Vasoactive intestinal peptide (see) (VIP) and Gastric inhibitory peptide (see) (GIP), and it is thought that these four hormones evolved from a common ancestral protein by a process of gene multiplication. 

The amino acid sequence of the hormone is (NII2)-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-(COOH). Using the genetic code, it is straightforward to deduce an appropriate DNA sequence that would code for this polypeptide. For production of the hormone in E. coli, the gene fusion method was used. 

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