Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors

Márta Korbonits, Richard A. Jacobs, Simon J.B. Aylwin, Jacky M. Burrin, Patricia L.M. Dahia, John P. Monson, Jürgen Honegger, Rudolf Fahlbush, Peter J. Trainer, Shern L. Chew, G. Michael Besser, Ashley B. Grossman

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Abstract

Synthetic GH secretagogues (GHSs; GH-releasing peptides and their nonpeptide mimetics) stimulate GH release, activate the hypothalamo- pituitary-adrenal axis, and release PRL in vivo. Patients with acromegaly show an exuberant GH response to GHSs, whereas patients with pituitary- dependent ACTH-secreting tumors show an exaggerated rise in ACTH and cortisol. We, therefore, studied the presence of GHS receptor (GHS-R) messenger ribonucleic acid (RNA) in 38 human pituitary tumors of different cell types, 3 ectopic ACTH-secreting tumors, a pancreatic gastrinoma, 3 insulinomas, and a nonsecreting thymic carcinoid as well as in 7 normal pituitary glands. Certain pituitary tumors were also studied by in vitro cell culture with measurement of secreted GH, ACTH, PRL, FSH, LH, α-subunit, and TSH. RNA was extracted from tissue samples and, after RT, a duplex PCR reaction with primers for the GHS-R gene and for the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase was performed, allowing semiquantitation of GHS-R expression. All the somatotroph adenomas (n = 8) showed a 2-10 times higher expression of the GHS-R gene compared to normal pituitaries. Higher than normal expression was shown in 5 of 18 tumors from patients with ACTH-secreting pituitary adenomas and in 1 of 3 ectopic ACTH- secreting carcinoid tumors. Two of the pituitary ACTH-secreting adenoma samples showed completely absent expression of the GHS-R, 8 showed expression similar to that of normal pituitary tissue, and 3 of the corticotroph adenoma tissue samples and 2 ectopic ACTH-secreting tumors showed a very low level of expression. One of 4 prolactinoma samples showed a high level of expression, 1 showed expression similar to that of normal pituitary, and 2 samples showed a very low level of expression. Nonfunctioning pituitary adenoma samples showed either absent or very low level expression of the GHS-R. The pancreatic gastrinoma sample showed expression similar to that of normal pituitary tissue, whereas 3 insulinomas showed low level expression of the GHS-R gene; a nonsecreting thymic carcinoid tumor showed no detectable expression. In summary, although GHS-R messenger RNA is abundant in human somatotroph adenomas, it is also present in other pituitary adenomas, particularly ACTH-secreting tumors. These findings may explain the in vivo responses to GHSs in patients harboring such tumors. It also appears from our study that GHS-R may be expressed in other neuroendocrine tumors.

Original languageEnglish (US)
Pages (from-to)3624-3630
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number10
DOIs
StatePublished - Nov 14 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Korbonits, M., Jacobs, R. A., Aylwin, S. J. B., Burrin, J. M., Dahia, P. L. M., Monson, J. P., Honegger, J., Fahlbush, R., Trainer, P. J., Chew, S. L., Besser, G. M., & Grossman, A. B. (1998). Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. Journal of Clinical Endocrinology and Metabolism, 83(10), 3624-3630. https://doi.org/10.1210/jc.83.10.3624