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  • Review Article
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Molecular targets in pituitary tumours

Key Points

  • Pituitary tumours are common and cause unrestrained hormone secretion or compression of intracranial structures. Treatment aims to suppress hormone hypersecretion, ablate tumours or prevent their growth without compromising endogenous pituitary function.

  • Hypothalamic and pituitary growth factors and their receptors regulate normal and abnormal pituitary-tumour hormone secretion and cell growth.

  • Pituitary tumours express various hormone receptors and retain inhibitory responses to agonistic and antagonistic ligands. Recent efforts have enabled the development of safe and potent anti-hormonal and anti-proliferative compounds aimed at specific pituitary-tumour-cell molecular targets and, potentially, other cancers.

  • First-generation dopamine-receptor agonists have been superceded by potent compounds with long-lasting effects and improved side-effect profiles. Treatment with somatostatin analogues is poised to broaden in application with the development of somatostatin-receptor subtype-specific and universal somatostatin analogues. Newer chimeric agonists that encompass dopaminergic actions as well as somatostatin-like actions are in development.

  • Peripheral growth-hormone-receptor antagonists (for example, pegvisomant) specifically block insulin-like growth factor 1 production. Retinoic-acid receptor and peroxisome-proliferator-activated receptor-γ also represent new approaches for treating pituitary tumours.

Abstract

Pituitary tumours are associated with unrestrained secretion and subsequent action of trophic hormones. One approach to therapy involves suppressing pituitary-hormone hypersecretion without compromising endogenous pituitary function. Identification of novel neuroendocrine-receptor targets has enabled the development of safe and effective receptor ligands that can be used to treat pituitary tumours and associated hormonal excess. Some of these agents, such as somatostatin analogues and a growth-hormone-receptor antagonist, will also have broader applications in treating other cancers and metabolic disorders.

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Figure 1: Anatomy of the pituitary gland.
Figure 2: Control of the hypothalamic–pituitary–target-organ axes.
Figure 3: Somatostatin and dopamine receptor signalling.
Figure 4: Action of growth-hormone-receptor antagonist.

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References

  1. Melmed, S. & Kleinberg, D. in Williams Textbook of Endocrinology 10th edn Ch. 8 (eds Larson, P. R., Kronenberg, H. M., Melmed, S. & Polonsky, K. S.) 177–279 (W. B. Saunders, Philadelphia, 2003). Comprehensive and up-to-date background information on pituitary structure and function.

    Google Scholar 

  2. Melmed, S. Mechanisms for pituitary tumorigenesis: the plastic pituitary. J. Clin. Invest. 112, 1603–1618 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sano, K. Incidence of primary tumors (1969–1983) in Brain Tumor Registry of Japan. Neurol. Med. Chir. 37, 391–441 (1992).

    Google Scholar 

  4. Schlechte, J. A. Clinical impact of hyperprolactinaemia. Baillieres Clin. Endocrinol. Metab. 9, 359–366 (1995).

    Article  CAS  PubMed  Google Scholar 

  5. Molitch, M. E. Medical management of prolactin-secreting pituitary adenomas. Pituitary 5, 55–65 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. Molitch, M. E. in The Pituitary 2nd edn (ed. Malden, M. A.) 455–495 (Blackwell Publishing, 2002)

    Google Scholar 

  7. Nabarro, J. D. Acromegaly. Clin. Endocrinol. 26, 481–512 (1987).

    Article  CAS  Google Scholar 

  8. Miller, G. M. et al. Somatostatin receptor subtype gene expression in pituitary adenomas. J. Clin. Endocrinol. 80, 1386–1392 (1995).

    CAS  Google Scholar 

  9. Larsson, C., Skogseid, B., Oberg, K., Nakamura, Y. & Nordenskjold, M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332, 85–87 (1988).

    Article  CAS  PubMed  Google Scholar 

  10. Chandrasekharappak, S. C. et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 276, 404–406 (1997). Describes the menin gene, which is one of the few characterized genes associated with familial pituitary-tumour syndromes.

    Article  Google Scholar 

  11. Casey, M. et al. Mutations in the protein kinase A R1α regulatory subunit cause familial cardiac myxomas and Carney complex. J. Clin. Invest. 106, R31–R38 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kirschner, L. S. et al. Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with Carney complex. Nature Genet. 26, 89–92 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Dotsch, J. et al. Gs α mutation at codon 201 in pituitary adenoma causing gigantism in a 6-year old boy with McCune–Albright syndrome. J. Clin. Endocrinol. Metab. 81, 3839–3842 (1996).

    CAS  PubMed  Google Scholar 

  14. Asa, S. L. & Ezzat, S. The pathogenesis of pituitary tumors. Nature Rev. Cancer 2, 836–849 (2002).

    Article  CAS  Google Scholar 

  15. Alexander, J. M. et al. Clinically non-functioning pituitary tumors are monoclonal in origin. J. Clin. Invest. 86, 336–340 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Herman, V., Fagin, J., Gonsky, R., Kovacs, K. & Melmed, S. Clonal origins of pituitary adenomas. J. Clin. Endocrinol. Metab. 71, 1427–1433 (1990). Seminal paper demonstrating that pituitary tumours are monoclonal expansions.

    Article  CAS  PubMed  Google Scholar 

  17. Thorner, M. O. et al. Somatotroph hyperplasia: successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth-hormone-releasing factor. J. Clin. Invest. 70, 965–977 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sano, T., Asa, S. L. & Kovacs, K. Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations. Endocr. Rev. 9, 357–373 (1988).

    Article  CAS  PubMed  Google Scholar 

  19. Lyons, J. et al. Two G protein oncogenes in human endocrine tumors. Science 249, 655–659 (1990). Describes the most common genetic mutation that is detected in sporadic pituitary tumours.

    Article  CAS  PubMed  Google Scholar 

  20. Spada, A. & Vallar, L. G-protein oncogenes in acromegaly. Horm. Res. 38, 90–93 (1992).

    Article  CAS  PubMed  Google Scholar 

  21. Zhang, X. et al. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J. Clin. Endocrinol. Metab. 84, 761–767 (1999).

    Article  CAS  PubMed  Google Scholar 

  22. Heaney, A. P. et al. Early involvement of estrogen-induced pituitary tumor transforming gene (PTTG) and fibroblast growth factor expression in prolactinoma pathogenesis. Nature Med. 5, 1317–1321 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. Shimon, I. & Melmed, S. Management of pituitary tumors. Ann. Intern. Med. 129, 472–483 (1998).

    Article  CAS  PubMed  Google Scholar 

  24. Greenman, Y. & Melmed, S. Diagnosis and management of non-functioning pituitary tumors. Ann. Rev. Med. 47, 95–106 (1996).

    Article  CAS  PubMed  Google Scholar 

  25. Mampalam, T. J., Tyrrell, J. B. & Wilson, C. B. Transsphenoidal microsurgery for Cushing's disease: a report of 216 cases. Ann. Intern. Med. 109, 487–493 (1988).

    Article  CAS  PubMed  Google Scholar 

  26. Simmons, N. E., Alden, T. D., Thorner, M. O. & Laws, E. R. Jr. Serum cortisol response to transphenoidal surgery for Cushing disease. J. Neurosurg. 95, 1–8 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Hoybye, C. et al. Adrenocorticotrophic hormone-producing pituitary tumors: 12 to 22-year follow-up after treatment with sterotactic radiosurgery. Neurosurgery 49, 284–291 (2001).

    CAS  PubMed  Google Scholar 

  28. Swearingen, B. et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J. Clin. Endocrinol. Metab. 83, 3419–3426 (1998).

    CAS  PubMed  Google Scholar 

  29. Freda, P. U., Wardlaw, S. L. & Post, K. D. Long-term endocrinologic follow-up after transsphenoidal surgery for acromegaly. J. Neurosurg. 89, 353–358 (1998).

    Article  CAS  PubMed  Google Scholar 

  30. Ebersold, M. J., Quast, L. M., Laws, E. R., Scheithauer, B. & Randall, R. V. Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J. Neurosurg. 64, 713–719 (1986).

    Article  CAS  PubMed  Google Scholar 

  31. Brada, M. et al. The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin. Endocrinol. 38, 571–578 (1993).

    Article  CAS  Google Scholar 

  32. Barrande, G. et al. Hormonal and metabolic effects of radiotherapy in acromegaly: long-term results in 128 patients followed in a single center. J. Clin. Endocrinol. Metab. 85, 3779–3785 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. Erfurth, E. M., Bulow, B., Mikoczy, Z. & Hagmar, L. Incidence of a second tumor in hypopituitary patients operated for pituitary tumors. J. Clin. Endocrinol. Metab. 86, 659–662 (2001).

    CAS  PubMed  Google Scholar 

  34. Freda, P. U. & Wardlaw, S. L. Primary medical therapy for acromegaly. J. Clin. Endocrinol. Metab. 83, 3031–3033 (1998).

    Article  CAS  PubMed  Google Scholar 

  35. Orth, D. N. Cushing's syndrome. N. Engl. J. Med. 332,791–803 (1995).

    Article  CAS  PubMed  Google Scholar 

  36. Reubi, J. C. et al. Somatostatin receptors in human endocrine tumours. Cancer Res. 47, 551–558 (1987).

    CAS  PubMed  Google Scholar 

  37. Casini-Raggi, C. et al. Somatostatin receptors in non-endocrine tumors. Minerva Endocrinol. 26, 149–158 (2001).

    CAS  PubMed  Google Scholar 

  38. Shimon, I. et al. Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. J. Clin. Invest. 100, 2386–2392 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Greenman, Y. & Melmed, S. Heterogenous expression of two somatostatin receptor subtypes in pituitary tumors. J. Clin. Endocrinol. Metab. 78, 398–403 (1994).

    CAS  PubMed  Google Scholar 

  40. Ballare, E. et al. Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatment. J. Clin. Endocrinol. Metab. 86, 3809–3814 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Melmed, S. Acromegaly. N. Engl. J. Med. 322, 966–977 (1990).

    Article  CAS  PubMed  Google Scholar 

  42. Lamberts, S. W., van Der Lely, A. J., de Herder, W. W. & Hofland, L. J. Octreotide. N. Engl. J. Med. 334, 246–254 (1994).

    Article  Google Scholar 

  43. Lamberts, S. W. J. et al. The sensitivity of growth hormone and prolactin secretion to the somatostatin analogue 201–995 in patients with prolactinomas and acromegaly. Clin. Endocrinol. 25, 201–212 (1986). Classical description of the developmental history and early use of somatostatin analogues.

    Article  CAS  Google Scholar 

  44. Ezzat, S. et al. Octreotide treatment of acromegaly. A randomized multicenter study. Ann. Intern. Med. 117, 711–718 (1992).

    Article  CAS  PubMed  Google Scholar 

  45. Newman, C. B. et al. Safety and efficacy of long term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients — a clinical research center study. J. Clin. Endocrinol. Metab. 80, 2768–2775 (1995).

    CAS  PubMed  Google Scholar 

  46. Vance, M. L. & Harris, A. G. Long term treatment of 189 acromegalic patients with the somatostatin analog octreotide. Results of a multicenter acromegaly study group. Arch. Int. Med. 151, 1573–1578 (1991).

    Article  CAS  Google Scholar 

  47. Legovini, P. et al. 111Indium-pentetreotide pituitary scintigraphy and hormonal responses to octreotide in acromegalic patients. J. Endocrinol. Invest. 20, 424–428 (1997).

    Article  CAS  PubMed  Google Scholar 

  48. Colao, A. et al. Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly. J. Clin. Endocrinol. Metab. 86, 2779–2786 (2001).

    CAS  PubMed  Google Scholar 

  49. Baldelli, R. et al. Two-year follow-up of acromegalic patients treated with slow release lanreotide (30 mg). J. Clin. Endocrinol. Metab. 85, 4099–4103 (2000).

    CAS  PubMed  Google Scholar 

  50. Freda, P. U. Somatostatin analogs in acromegaly. J. Clin. Endocrinol. Metab. 87, 3013–3018 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Hofland, L. J. & Lamberts, S. W. The pathophysiological consequences of somatostatin receptor internalisation and resistance. Endocr. Rev. 24, 28–47 (2003).

    Article  CAS  PubMed  Google Scholar 

  52. Melmed, S. et al. Consensus: guidelines for acromegaly management. J. Clin. Endocrinol. Metab. 87, 4054–4058 (2001).

    Article  CAS  Google Scholar 

  53. Patel, Y. et al. Molecular biology of somatostain receptor subtypes. Metabolism 45, 31–38 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. Culler, M. D., Taylor, J. E. & Moreau, J. P. Somatostatin receptor subtypes: targeting functional and therapeutic specificity. Ann. Endocrinol. 63, 2S5–12 (2002).

    CAS  Google Scholar 

  55. Ren, S. G. et al. Functional association of somatostatin receptor subtypes 2 and 5 in inhibiting human growth hormone secretion. J. Clin. Endo. Metab. 88, 4239–4245 (2003).

    Article  CAS  Google Scholar 

  56. Bruns, C., Lewis, I., Briner, U., Meno-Tetang, G. & Weckbecker, G. SOM230: a novel somatostatin peptidomimentic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profile. Eur. J. Endocrinol. 146, 707–716 (2002).

    Article  CAS  PubMed  Google Scholar 

  57. Hofland, L. J. et al. The novel somatostatin analog SOM230 has a broad spectrum of inhibitory action on hormone release by human somatotroph, corticotroph and PRL-secreting pituitary adenomas in vitro. Program 85th Annual Meeting of The Endocrine Society P2-449 (2003).

  58. van der Hoek, J. et al. A single dose comparison of the acute effects of the new somatostatin analog SOM230 and octreotide in acromegalic patients. Program 85th Annual Meeting of The Endocrine Society P1-625 (2003).

  59. Murray, R. D. et al. The universal somatostatin ligand (SOM230) regulates human growth hormone secretion: novel peptide therapy for acromegaly. Program 84th Annual Meeting of The Endocrine Society 58–56 (2002).

  60. Weckbecker, G., Briner, U., Lewis, I. & Bruns, C. SOM230: a new somatostatin peptidomimetic with potent inhibitory effects on the growth hormone/insulin-like growth factor-I axis in rats, primates, and dogs. Endocrinology 143, 4123–4130 (2002).

    Article  CAS  PubMed  Google Scholar 

  61. Sharma, K. & Srikant, C. B. Int. J. Cancer. 76, 259–266 (1998).

    Article  CAS  PubMed  Google Scholar 

  62. Pakes, D. Drug therapy: bromocriptine. N. Engl. J. Med. 301, 873–878 (1979).

    Article  Google Scholar 

  63. Besser, G. M., Parke, L., Edwards, C. R., Forsyth, I. A. & McNeilly, A. S. Galactorrhoea: successful treatment with reduction of prolactin levels by brom-ergocryptine. Br. Med. J. 3, 669–672 (1972). First paper to describe the use of D2-agonist therapy for prolactin-secreting tumours.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Vance, M. L., Evans, W. S. & Thorner, M. O. Drugs five years later. Bromocriptine. Ann. Intern. Med. 100, 78–91 (1984).

    Article  CAS  PubMed  Google Scholar 

  65. Klibanski, A. & Zervas, N. T. Diagnosis and management of hormone-secreting pituitary adenomas. N. Engl. J. Med. 324, 822–831 (1991).

    Article  CAS  PubMed  Google Scholar 

  66. Bevan, J. S., Webster, J., Burke, C. W. & Scanlon, M. F. Dopamine agonists and pituitary tumor shrinkage. Endocr. Rev. 13, 220–240 (1992).

    Article  CAS  PubMed  Google Scholar 

  67. Kleinberg, D. L. et al. Pergolide for the treatment of pituitary tumors secreting prolactin or growth hormone. N. Engl. J. Med. 309, 704–709 (1983).

    Article  CAS  PubMed  Google Scholar 

  68. Vance, M. L. et al. Treatment of prolactin-secreting pituitary macroadenomas with the long-acting non-ergot dopamine agonist CV 205-502. Ann. Intern. Med. 112, 668–673 (1990).

    Article  CAS  PubMed  Google Scholar 

  69. Bevan, J. S. & Davis, J. R. Cabergoline: an advance in dopaminergic therapy. Clin. Endocrinol. 41, 709–712 (1994).

    Article  CAS  Google Scholar 

  70. Colao, A. et al. Prolactinomas resistant to standard dopamine agonists respond to chronic cabergoline treatment. J. Clin. Endocrinol. Metab. 82, 876–883 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. Webster, J. et al. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group. N. Engl. J. Med. 331, 904–909 (1994).

    Article  CAS  PubMed  Google Scholar 

  72. Cunningham, B. C. et al. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science 254, 821–825 (1991).

    Article  CAS  PubMed  Google Scholar 

  73. Kopchick, J. J., Parkinson, C., Stevens, E. C. & Trainer, P. J. Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocr. Rev. 23, 623–646 (2002). Describes the developmental molecular rationale and mechanism of action of growth-hormone-receptor antagonists.

    Article  CAS  PubMed  Google Scholar 

  74. Kohn, D. T. & Kopchick, J. J. Growth hormone receptor antagonists. Minerva Endocrinol. 27, 287–298 (2002).

    CAS  PubMed  Google Scholar 

  75. Frank, S. J. Receptor dimerization in GH and erythropoietin action: it takes two to tango. Endocinology 143, 2–10 (2002)

    Article  CAS  Google Scholar 

  76. Trainer, P. J. et al. Treatment of acromegaly with the growth hormone receptor antagonist pegvisomant. N. Eng. J. Med. 342, 1171–1177 (2000).

    Article  CAS  Google Scholar 

  77. Bonert, V. S., Zib, K., Scarlett, J. A. & Melmed, S. Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. J. Clin. Endocrinol. Metab. 85, 2958–2961 (2000).

    Google Scholar 

  78. van der Lely, A. J. et al. Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet. 358, 1754–1759 (2001).

    Article  CAS  PubMed  Google Scholar 

  79. Sheppard, M. C. Primary medical therapy for acromegaly. Clin. Endocrinol. 58, 387–399 (2003).

    Article  Google Scholar 

  80. Flogstad, A. K. et al. A comparison of octreotide, bromocriptine, or a combination of both drugs in acromegaly. J. Clin. Endocrinol. Metab. 79, 461–465 (1994).

    CAS  PubMed  Google Scholar 

  81. Saveanu, A. et al. Demonstration of enhanced potency of a chimeric somatostain-dopamine molecule, BIM-23A387, in suppressing growth hormone and prolactin secretion from human pituitary somatotroph adenoma cells. J. Clin. Endocrinol. Metab. 87, 5545–5552 (2002).

    Article  CAS  PubMed  Google Scholar 

  82. Ren, S. G. et al. Suppression of rat and human growth hormone and prolactin secretion by a novel somatostatin/dopaminergic chimeric ligand. J. Clin. Endocrinol. Metab. 11, 5414–5421 (2003).

    Article  CAS  Google Scholar 

  83. Musset, F., Bertrand, P., Kordon, C. & Enjalbert, A. Differential coupling with pertussis toxin-sensitive G proteins of dopamine and somatostatin receptors involved in regulation of adenohypophyseal secretion. Mol. Cell Endocrinol. 73, 1–10 (1990).

    Article  CAS  PubMed  Google Scholar 

  84. Rocheville, M. et al. Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 288, 154–157 (2000). First paper to demonstrate heterodimerization of the G-protein-coupled dopamine and somatostatin receptors.

    Article  CAS  PubMed  Google Scholar 

  85. Forman, B. M. et al. 15-Deoxy-δ 12,14-prostaglandin J1 is a ligand for the adipocyte determination factor PPAR γ. Cell 83, 803–812 (1995).

    Article  CAS  PubMed  Google Scholar 

  86. Elstner, E. et al. Ligands for peroxisome proliferator-activated receptor-γ and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc. Natl Acad. Sci. USA 95, 8806–8811 (1988).

    Article  Google Scholar 

  87. Kubota, T. et al. Ligand for peroxisome proliferator-activated receptor γ (troglitazone) has potent anti-tumor effects against prostate cancer both in vitro and in vivo. Cancer Res. 58, 3344–3352 (1998).

    CAS  PubMed  Google Scholar 

  88. Heaney, A. P., Fernando, M., Yong, W. & Melmed, S. Functional PPAR-γ receptor represents a novel therapeutic target in Cushing's disease. Nature Med. 11, 1281–1287 (2002).

    Article  CAS  Google Scholar 

  89. Heaney, A. P., Fernando, M. & Melmed, S. PPAR-γ receptor ligands: a novel therapy for pituitary tumors. J. Clin. Invest. 111, 1381–1388 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Nieman, L. Medical therapy of Cushing's disease. Pituitary 5, 77–82 (2003).

    Article  Google Scholar 

  91. Gudas, L. J., Sporn, M. B. & Roberts, A. B. in The Retinoids: Biology, Chemistry, and Medicine. (eds Sporn, M. B., Roberts, A. B. & Goodman, D. S.) 443–520 (Raven, New York, 1994).

    Google Scholar 

  92. Pitha-Rowe, I., Petty, W. J., Kitareewan, S. & Dmitrovsky, E. Retinoid target genes in acute promyelocytic leukemia. Leukemia 17, 1723–1730 (2003).

    Article  CAS  PubMed  Google Scholar 

  93. Kurie, J. M. The biologic basis for the use of retinoids in cancer prevention and treatment. Curr. Opin. Oncol. 11, 497–502 (1999). Good review of rationale and potential therapeutic use of retinoids in cancer.

    Article  CAS  PubMed  Google Scholar 

  94. Rizvi, N. A. et al. A phase I study of LGD1069 in adults with advanced cancer. Clin. Cancer Res. 5, 1658–1664 (1999).

    CAS  PubMed  Google Scholar 

  95. Koeffler, H. P. Peroxisome proliferator-activated receptor γ and cancers. Clin. Cancer Res. 9, 1–9 (2003).

    CAS  PubMed  Google Scholar 

  96. Paez-Pereda, M. et al. Retinoic acid prevents experimental Cushing syndrome. J. Clin. Invest. 108, 1123–1131 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Colombo, P. et al. Effects of long-term treatment with the gonadotrophin-releasing analog nafarelin in patients with non-functioning pituitary adenomas. Eur. J. Endocrinol. 130, 339–345 (1994).

    Article  CAS  PubMed  Google Scholar 

  98. Schally, A. V. & Nagy, A. New approaches to treatment of various cancers based on cytotoxic analogs of LHRH, somatostatin and bombesin. Life. Sci. 11, 2305–2320 (2003).

    Article  CAS  Google Scholar 

  99. Horwitz, G. A., Miklovsky, I., Heaney, A. P., Ren, S. G. & Melmed, S. Human pituitary tumor-transforming gene (PTTG1) motif suppresses prolactin expression. Mol. Endocrinol. 17, 600–609 (2003)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Work in the authors' laboratories is supported by grants from the National Institutes of Health (S.M.), the Doris Factor Molecular Endocrinology Laboratory (S.M.), the Annenberg Foundation (S.M. & A.P.H.) and the Margaret Early Trust (A.P.H.).

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DATABASES

Cancer.gov

pituitary cancer

LocusLink

BAX

BCL2

CDKN2A

FOS

GnRH

GnRHR

GSP

GH

GHRH

HST1

MEN1

MYC

NUR77

NURR1

p53

POMC

PPARγ

PTTG

PRL

RARα

RARβ

RARγ

RAS

RB

RXRα

RXRβ

RXRγ

SSTR1

SSTR2

SSTR3

SSTR4

SSTR5

FURTHER INFORMATION

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Glossary

THYROTOXICOSIS

A clinical condition in which there is pathologically excessive production of thyroid hormones. The most common form is Grave's disease. Others include subacute thyroiditis and Hashimoto's disease.

MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 SYNDROME

An autosomal dominant disorder, features of which include pituitary and parathyroid adenomas, and/or tumours of the endocrine pancreas.

CARNEY COMPLEX

An autosomal dominant disorder that is characterized by cutaneous pigmentation, atrial and other myxomas, schwannomas, and endocrine overactivity, most commonly adrenocorticotropin-hormone- and/or growth-hormone-secreting pituitary adenomas or thyroid adenomas, in association with spotty skin pigmentation.

McCUNE–ALBRIGHT SYNDROME

Also known as precocious puberty, Cushing's syndrome, thyrotoxicosis and gigantism, this syndrome is characterized by polyostotic fibrous dysplasia, cutaneous hyperpigmentation and endocrine overactivity. Patients carry mutations in the GSP gene that lead to overactivation of adenyl cyclase, resulting in somatotroph hyperplasia and growth-hormone hypersecretion.

TRANSSPHENOIDAL

A microsurgical approach that represents the most accessible and minimally traumatic corridor for removing a tumour of the pituitary gland. In this approach, the anterior face of the sphenoid bone is reached by tunnelling under the submucosa of the nose or under the lip.

NON-FUNCTIONING PITUITARY TUMOURS

Pituitary tumours that are not associated with increased serum hormone levels in patients.

ERGOT

Ergot is caused by the fungus Claviceps purpurea that infects various plants, including rye, cereals and grass. Ergot derivatives have had several uses in the field of medicine. Ergotamine was a former treatment for migraine headaches, but can cause gangrene with chronic use. Other derivatives include the psychotomimetic drug lysergic acid and bromocriptine, which binds the dopamine D2 receptor to lower serum prolactin levels.

CHIMERIC LIGAND

A hybrid compound that combines characteristics of ligands that interact with two different receptors.

PERTUSSIS-SENSITIVE G-PROTEINS

Pertussis toxin covalently modifies the α subunits of numerous G proteins (Gαi,Gαo) by ADP-ribosylation, uncoupling the G protein from its receptor.

ALTERNATIVE PROMOTER USAGE

Differential gene regulation exercised through use of an alternative, often tissue-specific regulatory site, located at variable distances upstream of the known promoter.

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Heaney, A., Melmed, S. Molecular targets in pituitary tumours. Nat Rev Cancer 4, 285–295 (2004). https://doi.org/10.1038/nrc1320

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