OBJECTIVES: It has been suggested that ghrelin synthesized locally in pituitary regulates the function and growth of pituitary cells in autocrine/paracrine way and might be an important factor of pituitary tumorogenesis. The expression of ghrelin receptor in neoplastic cells of pituitary adenomas has also been demonstrated. In vitro studies confirmed that ghrelin stimulates the proliferation of somatotroph cells in GH3 cell line. The presence of both ghrelin mRNA and protein was detected in a number of benign and malignant neoplasms as well as in neoplastic cells of the tissues which do not express ghrelin in physiological conditions. This study showed the presence of ghrelin mRNA and its protein in different types of pituitary adenomas.
DESIGN: The samples of 37 pituitary adenomas were obtained during standard neurosurgical tumor removal. The study tissues included 20 somatotroph tumors (15 patients treated and 5 patients untreated with octreotide LAR before the surgery), 12 nonfunctioning adenomas, 4 prolactinomas and 1 ACTH-secreting tumor. The control included samples of normal mucous membrane of the stomach and normal pituitaries. Expression of ghrelin mRNA was studied in 28 pituitary adenomas by RT-PCR. Immunohistochemical evaluation of ghrelin presence was performed in 34 tumors.
RESULTS: The presence of ghrelin gene transcripts was demonstrated in 10 out of 15 examined somatotroph tumors (obtained from patients treated with octreotide LAR before the surgery) and also in 2 out of 4 samples of prolactinomas, 7 out of 8 of nonfunctioning tumors and in 2 samples of normal pituitary. Immunohistochemical analyses revealed the presence of the protein in all 5 examined somatotroph tumors obtained from patients not treated prior to the surgery and in 10 out of 15 tumors obtained from patients treated with octreotide LAR. The peptide was detected also in 10 out of 12 examined nonfunctioning tumors and in 2 examined PRL-secreting tumors. The immunostaining for ghrelin was not shown in normal pituitaries.
CONCLUSIONS: The study demonstrated that ghrelin gene is expressed in somatotroph adenomas, both treated and untreated with octreotide LAR before the surgery, and also in other types of pituitary adenomas (prolactinomas and nonfunctioning adenomas)....