FIGURE 5-19 Members of the hematopoietic-cytokine receptor family that includes the receptors for PRL and GH. Selected amino acids of each receptor are numbered. Homologous regions reside in the extracellular domains, marked at the amino-terminal end by the pairs of cysteines (C1-C4, indicated by thin lines). A common WSXWS motif is indicated by the thick line. The transmembrane regions are in black. Adapted from Kelly, P. A., Djiane, J., Postel-Vinay, M. C., Edery, M. (1991). The prolactin/growth hormone receptor family. Endocr Rev. 12, 235-251. © The Endocrine Society, 1991. Reproduced with permission from Cooke, N. E. (1995). Prolactin: Basic physiology. In "Endocrinology" (L. J. DeGroot, ed.), 3rd ed., Vol. 1, pp. 368-393. W. B. Saunders Co., Philadelphia, PA.

suiting in the breakdown of vascular polysaccharides to glucose, which enters circulation.

One form of dwarfism in humans is caused by the defective production of pituitary GH. This condition appears from an autosomal recessive characteristic. Dwarfs in this category completely lack GH but not other pituitary hormones. Treatment of the condition with hGH causes prompt antibody reaction in that the dwarf recognized hGH as a xenobiotic. Through the use of cDNA probes of hGH, there appear to be several hybridizing bands corresponding to this cDNA. Dwarfs lack one of these bands, however, and their immediate family members have this band but in less than normal amounts. The normal GH gene encodes a 22-kDa GH, while the variant encodes, through an alternative splicing event, a 20-kDa GH. A third form of GH also exists that is not very well studied. The 22-kDa form has the growth-stimulating function, but not the hyperglycemic effect that is characteristic of the splice variant form. The ratio of these two forms in the blood is fairly constant in spite of the 22-kDa form being more concentrated in the pituitary. The nearly equal ratio between the two circulating forms may be accounted for by the slower degradation of the 20-kDa splice variant. The fairly constant circulating ratio between the two forms is also independent of age from child to adult, except that GH levels are higher at puberty and decline during senescence. In addition, the responsiveness of the pituitary to releasing factors undoubtedly decreases with aging.

Like many of the other pituitary hormones, the secretion of GH from the pituitary is pulsatile, and peaks of GH secretion can occur throughout a 24-hr period although the magnitude of the peaks can vary with a number of factors, one of which is sleep, during which GH levels are usually higher. The levels of other pituitary hormones also change during sleep but GH is a hallmark. It is not clear what GH is doing in this state, but it could be related to its action on carbohydrate metabolism (Figure 5-23).

AA-26 AA-23 AA32 AA72 AA127 AA191

AA-26 AA-23 AA32 AA72 AA127 AA191

Pre 22k hgH m RNA „ . Pre 20k hgH m RNA

100 bp

FIGURE 5-20 Theoretical representation of the hGH gene and the mRNA from it. The hGH gene contains three introns: intron A between amino acids (AA) 24 and 25, intron B between AA 31 and 32, and intron C between AA 71 and 72. These are excised when the gene is transcribed into the mRNA for the 22-kDa hGH. Also shown is the alternative splicing transcribed into the mRNA of 20-kDa hGH. Reprinted with permission from Chawla, R. J., Parks, J. H., and Rudman, D. (1983). Structural variants of human growth hormone: Biochemical, genetic and clinical aspects. Ann. Rev. Med. 34, 519-547. Copyright © 1983 by Annual Reviews, Inc. Reprinted with permission from Daughaday, W. H. (1995). Growth hormone, insulin-like growth factors, and acromegaly. In "Endocrinology" (L. J. De Groot, ed.). 3rd ed., Vol. 1, pp. 303-329. W. B. Saunders Co., Philadelphia, PA.


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