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Thyroid Factor

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hPTH KRSVSEIQLMHNLGK PTHrP KRAVSEHQLLHDKGK

FIGURE 9-3 Comparison of the size and amino acid sequence of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP). Reproduced with permission from Broadus, A. E., Mangin, M., Ikeda, K., Insogna, K. L., Weir, E. C., Burtis, W. J., and Stewart, A. F. (1988). New. Engl. J. Med. 319, 556-563.

hPTH KRSVSEIQLMHNLGK PTHrP KRAVSEHQLLHDKGK

FIGURE 9-3 Comparison of the size and amino acid sequence of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP). Reproduced with permission from Broadus, A. E., Mangin, M., Ikeda, K., Insogna, K. L., Weir, E. C., Burtis, W. J., and Stewart, A. F. (1988). New. Engl. J. Med. 319, 556-563.

acids allows PTHrP to mimic many of the biological actions of PTH (see later discussion).

C. Calcitonin

Calcitonin (CT) is a small polypeptide hormone secreted by the ultimobranchial gland in fish, amphibians, reptiles, and birds; in mammals it is secreted by the specialized C cells that are found primarily in the thyroid gland, but also at a small number of extrathy-roidal sites. The amino acid sequences of nine calcitonins have been determined; these include five mammalian species—porcine, bovine, ovine, human, and rat—as well as four nonmammalian species—salmon I, II, and III and eel. All have a similar structure consisting of a straight chain peptide of 32 amino acids, with a seven-membered disulfide ring at the N-terminus and a prolinamide residue at the C-terminus. Compared to the mammalian calcitonins, the nonmammalian hormones are much more stable and have a potency 10-50 times greater.

Studies of the molecular biology of the biosynthesis of calcitonin mRNA have demonstrated that the calcitonin gene can support the production of multiple protein products from a single transcription unit (see Figure 9-4). Thus, the same gene produces, as a consequence of alternative processing of RNA transcripts, the hormone calcitonin in the thyroid and a protein termed the calcitonin gene-related peptide (CGRP) in the hypothalamus. CGRP thus represents a putative hormone that was discovered through the application of recombinant DNA methodology without prior knowledge of its structure or biological function. As yet the biological function of CGRP has not been clearly defined; it is distributed selectively in neural tissues and has been postulated to be involved with nociception (the ability to perceive noxious stimuli), ingestive behavior, and modulation of the autonomic and nervous systems.

The discovery that alternative mRNA processing can produce multiple protein products may provide insight into the mechanisms by which endocrine genes increase the diversity and specificity of their biological responses. Calcitonin may be measured via bioassay or radioimmunoassay. The bioassay of calcitonin is based on the hypocalcemic actions of the peptide. Several radioimmunoassays for calcitonin have been developed; the radioimmunoassay for human calcitonin is important in the detection and treatment of medullary carcinoma of the thyroid.

D. Vitamin D

The molecular structure of vitamin D is closely allied to that of classical steroid hormones (see Figure 9-5). Technically, vitamin D is a secosteroid. Secosteroids

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