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Molecular Mechanisms of Endocrine Disorders

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Molecular Diagnostics

Part of the book series: Pathology and Laboratory Medicine ((PLM))

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Abstract

Molecular biologic methods and findings have had a major impact in clinical endocrinology. As a result, new concepts of hormone action have developed, major disease mechanisms have been defined, and new diagnostic strategies and therapies have been made possible. This chapter will summarize this rapidly evolving field with particular emphasis on clinical understanding and the application of molecular biologic techniques to clinical endocrine diagnosis. As a result of the pace of development, this chapter and any review will necessarily be selective, and will provide at best a window into a rapid and dynamically evolving area of clinical interest and increasing molecular understanding.

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References

  1. Rugarli, M. O. and Ballabio, A. Kallman syndrome. From genetics to neurobiology. JAMA 270:2713–2716, 1993.

    Article  PubMed  CAS  Google Scholar 

  2. Miller, W. Editorial: molecular genetics of familial central diabetes insipidus. J. Clin. Endocrinol. Metab. 77:592–594, 1993.

    Article  PubMed  CAS  Google Scholar 

  3. Rosenthal, W., Seibold, A., Antaramian, A., Lonergan, M., Arthus, M. F., Hendy, G. N., Birnbaumer, M., and Bichet, D. G. Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature 359:233–235, 1992.

    Article  PubMed  CAS  Google Scholar 

  4. Cogan, J. D., Phillips, J. A., Schenkman, S. S., Milner, R. D., and Sakati, N. Familial growth hormone deficiency: a model of dominant and recessive mutations affecting a monomeric protein. J. Clin. Endocrinol. Metab. 79:1261–1265, 1994.

    Article  PubMed  CAS  Google Scholar 

  5. Haugen, B. and Ridgway, E. C. Transcription factor Pit-1 and its clinical implications: from bench to bedside. Endocrinologist 5:132–139, 1995.

    Article  Google Scholar 

  6. Amselem, S., Duquesnoy, P., and Goossens, M. Molecular basis of Laron’ s dwarfism. Trends Endocr. Metab. 2:35–40, 1991.

    Article  CAS  Google Scholar 

  7. Goddard, A. D., Covello, R. C., Louh, S., Clakson, T., Attie, K. M., Gesundheit, N., Rundle, A., Wells, J. A., and Carlsson, L. M. Mutations of the growth hormone receptor in children with idiopathic short stature. New Engl. J. Med. 333:1093–1098, 1995.

    CAS  Google Scholar 

  8. Merimee, T. J., Baumann, G., and Daughaday, W. H. Growth hormone binding proteins, II: studies in pygmies and normal statured subjects. J. Clin. Endocrinol. Metab. 71:1183– 1188, 1990.

    Google Scholar 

  9. Landis, C. A. GTPase inhibiting mutations activate the a chain of Gs and stimulate adenylyl cyclase in human pituitary tumors. Nature 340:692–696, 1989.

    Article  PubMed  CAS  Google Scholar 

  10. Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J. M., Maroteaux, P., LeMerer, M., and Munnich, A. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature 371:252–254, 1994.

    Article  PubMed  CAS  Google Scholar 

  11. Kopp, P., van Sande, J., Parma, J., Duprez, L., Gerber, H., Joss, E., Jameson, J. L., Dumont, J. E., Vassart, G. Congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene. New Engl. J. Med. 331:150–154, 1995.

    Google Scholar 

  12. Sunthornthevarakul, T., Gottschalk, M., Hayashi, Y., and Refetoff, S. Brief report: resis-tance to thyrotropin caused by mutations in the thyrotropin-receptor gene. New Engl. J. Med. 332:155–160, 1995.

    Google Scholar 

  13. Usala, S. and Weintraub, B. Thyroid hormone resistance syndromes. Trends Endocr. Metab. 2:140–44, 1991.

    Article  CAS  Google Scholar 

  14. Refetoff, S., Weiss, R. E., and Usala, S. J. The syndromes of resistance to thyroid hor-mone. Endocr. Rev. 14:284–335, 1993.

    Google Scholar 

  15. Farid, N. R., Shi, Y., and Zou, M. Molecular basis of thyroid cancer. Endocr. Rev. 15:202– 232, 1994.

    Google Scholar 

  16. Arnold, A. Molecular genetics of parathyroid gland neoplasia. J. Clin. Endocrinol. Metab. 77:1108–1111, 1993.

    Article  CAS  Google Scholar 

  17. Schipani, E., Kruse, K., and Juppner, H. A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science 268:98–100, 1995.

    Article  PubMed  CAS  Google Scholar 

  18. Brown, E. M., Pollak, M., Seidman, C., Seidman, J. G., Chou, Y. W., Riccardi, D., and Hebert, S. C. Calcium-ion sensing cell-surface receptors. New Engl. J. Med. 333:234– 240, 1995.

    Google Scholar 

  19. Jalal, S. M., Crifasi, P. A., Karnes, P. S., and Michels, W. Cytogenetic testing for Will-iams syndrome. Mayo Clin. Proc. 71:67,68.

    Google Scholar 

  20. Driscoll, D. A., Budark, M. L., and Emanuel, B. S. A genetic etiology for Di-George syndrome: consistent deletions and microdeletions of 22q1 1. Am. J. Hum. Genet. 50:924–933, 1992.

    PubMed  CAS  Google Scholar 

  21. Larson, C., Shepherd, J., Nakamura, Y., Blomberg, C., Weber, G., Werelius, B., Hayward, N., The, B., Tokino, T., Seizinger, B., Skogseid, B., Oberg, K., and Nordenskjold, M. Predictive testing for multiple endocrine n. eoplasia type 1 using DNA polymorphisms. J. Clin. Invest. 89:1344–1349, 1992.

    Article  Google Scholar 

  22. Levine, M. A., Vechio, J. D., and Miric, A. Heterogeneous mutations in the gene encoding the α-subunit of the stimulatory G protein of adenylyl cyclase in Albright hereditary osteodystrophy. J. Clin. Endocrinol. Metab. 76:1560–1568, 1993.

    Article  Google Scholar 

  23. Clapham, D. E. Signal transduction. Why testicles are cool. Nature 371:109,110, 1994.

    Google Scholar 

  24. Hughes, M., Malloy, P., Kieback, D., Kesterson, R. Pike, J., Feldman, D., and O’ Malley, B. Point mutations in the human vitamin D receptor gene associated with hypocalcemic rickets. Science 242:1702–1705, 1988.

    Article  PubMed  CAS  Google Scholar 

  25. Weber, A., Toppari, R. D., Harvey, R. C., Klan, C., Shaw, N., Ricker, A. T., Nanto-Salonen, A. T., Vevan, J. S., and Clark, A. J. L. Adrenocorticotropin receptor gene muta-tions in familial glucocorticoid deficiency: relationships with clinical features in four families. J. Clin. Endocrinol. Metab. 80:65–71, 1995.

    Article  PubMed  CAS  Google Scholar 

  26. Yanase, T., Simpson, E. R., and Waterman, M. R. 17α-Hydroxylase/17,20 lyase defi-ciency: from clinical investigation to molecular definition. Endocr. Rev. 12:91–104, 1992.

    Article  Google Scholar 

  27. Mebarki, F., Sanchez, R., Rheaume, E., Laflamme, N., Simard, J., Forest, M. G., Bey-Omar, F., David, M., Labrie, F., and Morel, Y. Nonsalt-losing male pseudo-hermaphroditism due to the novel homozygous N100S mutation in the type II 3b-hydroxysteroid dehydrogenase gene. J. Clin. Endocrinol. Metab. 80:2127–2134, 1995.

    Article  CAS  Google Scholar 

  28. Mercado, A. B., Wilson, R. C., Cheng, K. C., Wei, J. Q., and New, M. I. Prenatal treat-ment and diagnosis of congenital adrenal hyperplasia owing to steroid 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 80:2014–2020, 1995.

    Article  PubMed  CAS  Google Scholar 

  29. White, P. C., Curnow, K. M., and Pascoe, L. Disorders of steroid 1 lβ -hydroxylase isozymes. Endocr. Rev. 15: 421–438, 1994.

    PubMed  CAS  Google Scholar 

  30. Malchoff, D. M., Brufsky, A., Reardon, G., McDermott, P., Javier, E. C., Bergh, C. H., Rowe, D., and Malchoff, C. D. A point mutation of the human glucocorticoid receptor in primary cortisol resistance. J. Clin. Invest. 91:1918–1925, 1993.

    Article  CAS  Google Scholar 

  31. Karl, M., Lamberts, S. W. J., Detera-Wadleigh, S. D., Encio, I. J., Stratakis, C. A., Hurley, D. M., Accili, D., and Chrousos, G. P. Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. J. Clin. Endocrinol. Metab. 76:683–689, 1993.

    Article  CAS  Google Scholar 

  32. Stewart, P. M., Murry, B. A., and Mason, J. I. Human kidney 1 1β-hydroxysteroid dehy-drogenase is a high affinity nicotinamide adenine dinucleotide-dependent enzyme and differs from the cloned type I isoform. J. Clin. Endocrinol. Metab. 79:480–484, 1994.

    Article  PubMed  CAS  Google Scholar 

  33. Shimkets, R. A., Warnock, D. G., Bositis, C. M., Nelson-Williams, C., Hansson, J. H., Schambelan, M., Gill, J. R., Ulick, S., Milora, R. V., Findling, J. W., Canessa, C. M., Rossier, C. B., and Lifton, R. P. Liddle’ s syndrome: heritable human hypertension caused by mutations in the β subunit of the epithelial sodium channel. Cell 79:407–414, 1994.

    Article  PubMed  CAS  Google Scholar 

  34. McPhaul, M. J., Marcelli, M., Zoppi, S., Griffin, J. E., and Wilson, J. D. The spectrum of mutations in the androgen receptor gene that causes androgen resistance. J. Clin. Endocrinol. Metab. 76:17–23, 1993.

    Article  PubMed  CAS  Google Scholar 

  35. Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R., Lubahn, D. B., and Korach, K. S. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. New Engl. J. Med. 331:1056–1061, 1994.

    CAS  Google Scholar 

  36. Homaki, A. H., Dieguez Lucena, J. L., Pakarinen, P., Sistonen, P., Tapanaienen, J., Gromoll, J., Laskikari, R., Sankila, E. M., Lehvaslaiho, H., Engel, A. R., Nieschlag, E., Huhtaniemi, 1., and de La Chapelle, A. Mutation of the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82:959–968, 1995.

    Article  Google Scholar 

  37. Shenker, A., Laue, L., Kosugi, S., Merendino, J. J., Minegishi, T., and Cutler, G. B. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature 365:652–654, 1993.

    Article  PubMed  CAS  Google Scholar 

  38. Jager, R. J., Anvret, M., Hall, K., and Scherer, G. A human XY female with a frame shift mutation in the candidate testis-determining gene SRY. Nature 348:352–354, 1990.

    Article  Google Scholar 

  39. Berta, P., Hawkins, J. R., Sinclair, A. H., Taylor, A., Griffiths, B. L., Goodfellow, P. N., and Fellous, M. Genetic evidence equating SRY and the testis-determining factor. Nature 348:448–450, 1990.

    Article  PubMed  CAS  Google Scholar 

  40. Weinstein, L., Shenker, A., Gejman, P., Merino, M., Friedman, E., and Spiegel, A. Acti-vating mutations of the stimulatory G protein in the McCune-Albright syndrome. New Engl. J. Med. 325:1688–1695.

    Google Scholar 

  41. Malchoff, C. D., Reardon, G., MacGillivray, D., Yamase, H., Rogol, A. D., and Malchoff, D. M. An unusual presentation of McCune-Albright syndrome confirmed by an acti-vating mutation of the Gsa-subunit from a bone lesion. J. Clin. Endocrinol. Metab. 78:803–806, 1994.

    Article  PubMed  CAS  Google Scholar 

  42. Goldstein, J. L. and Brown, M. S. Familial hypercholesterolemia, in The Molecular Basis ofInherited Disease, 6th ed., McGraw Hill, New York, pp. 1215–1250, 1989.

    Google Scholar 

  43. Brewer, H. B., Santamarina-Fojo, S., and Hoeg, J. M. Genetic defects in the human plasma apolipoproteins. Atherosclerosis Rev. 20:51–60, 1992.

    Google Scholar 

  44. Johns, D. R. Mitochondrial DNA and disease. New Engl. J. Med. 333:638–644, 1995.

    Article  PubMed  CAS  Google Scholar 

  45. Frougel, P., Zouali, H., Vionnet, N., Velho, G., Vaxillaire, M., Sun, F., Lesage, S., Stoffel, M., Takeda, J., and Passa P. Familial hyperglycemia due to mutations in glucokinase New Engl. J. Med. 328:697–702, 1993.

    Article  Google Scholar 

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Authors
  1. Bruce F. Bower
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  2. Carl D. Malchoff
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Editor information

Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    William B. Coleman

  2. Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT, USA

    Gregory J. Tsongalis

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© 1997 Springer Science+Business Media New York

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Bower, B.F., Malchoff, C.D. (1997). Molecular Mechanisms of Endocrine Disorders. In: Coleman, W.B., Tsongalis, G.J. (eds) Molecular Diagnostics. Pathology and Laboratory Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2588-9_12

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  • DOI: https://doi.org/10.1007/978-1-4757-2588-9_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-2590-2

  • Online ISBN: 978-1-4757-2588-9

  • eBook Packages: Springer Book Archive

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