Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors.
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-secret...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1998
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| _version_ | 1797075800042766336 |
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| author | Korbonits, M Jacobs, R Aylwin, S Burrin, J Dahia, P Monson, J Honegger, J Fahlbush, R Trainer, P Chew, S Besser, G Grossman, AB |
| author_facet | Korbonits, M Jacobs, R Aylwin, S Burrin, J Dahia, P Monson, J Honegger, J Fahlbush, R Trainer, P Chew, S Besser, G Grossman, AB |
| author_sort | Korbonits, M |
| collection | OXFORD |
| description | 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 non-secreting 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, alpha-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. |
| first_indexed | 2024-03-06T23:55:18Z |
| format | Journal article |
| id | oxford-uuid:74025784-4f70-4dc8-bbd8-ae7d9031087e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:55:18Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:74025784-4f70-4dc8-bbd8-ae7d9031087e2022-03-26T20:00:03ZExpression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:74025784-4f70-4dc8-bbd8-ae7d9031087eEnglishSymplectic Elements at Oxford1998Korbonits, MJacobs, RAylwin, SBurrin, JDahia, PMonson, JHonegger, JFahlbush, RTrainer, PChew, SBesser, GGrossman, ABSynthetic 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 non-secreting 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, alpha-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. |
| spellingShingle | Korbonits, M Jacobs, R Aylwin, S Burrin, J Dahia, P Monson, J Honegger, J Fahlbush, R Trainer, P Chew, S Besser, G Grossman, AB Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. |
| title | Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. |
| title_full | Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. |
| title_fullStr | Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. |
| title_full_unstemmed | Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. |
| title_short | Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. |
| title_sort | expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors |
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