In the nucleus, the gene for the hormone is tran- scribed into an mRNA. Generally, a single gene is responsible for directing the primary structure of each peptide hormone. (Because the genes for almost all peptide hormones have been cloned, recombinant DNA technology makes it possible to synthesize human peptide hormones.) 2. The hormone mRNA is transferred to the cytoplasm and translated on the ribosomes to the first protein pro- duct, a preprohormone. Translation of the mRNA begins with a signal peptide at the N terminus. Translation ceases, and the signal peptide attaches to receptors on the endoplasmic reticulum via “docking proteins.” Translation then continues on the endoplasmic reticulum until the entire peptide sequence is produced (i.e., the preprohormone). 3. The signal peptide is removed in the endoplasmic reticulum, converting the preprohormone to a prohormone. The prohormone contains the complete hormone sequence plus other peptide sequences, which will be removed in a final step. Some of the “other” peptide sequences in the pro- hormone are necessary for proper folding of the hormone (e.g., formation of intramolecular linkages). 4. The prohormone is transferred to the Golgi appa- ratus, where it is packaged in secretory vesicles. In the secretory vesicles, proteolytic enzymes cleave peptide sequences from the prohormone to produce the final hormone. Other functions of the Golgi apparatus include glycosylation and phosphoryla- tion of the hormone. 5. The final hormone is stored in secretory vesicles until the endocrine cell is stimulated. For example, parathyroid hormone (PTH) is synthesized and stored in vesicles in the chief cells of the parathyroid gland. The stimulus for secretion of PTH is low extracellular calcium (Ca 2+ ) concentration. When sensors on the parathyroid gland detect a low extra- cellular Ca 2+ concentration, the secretory vesicles are translocated to the cell membrane, where they extrude PTH into the blood by exocytosis. The other constituents of the secretory vesicles, including
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