gastrin-releasing-peptide and Pituitary-Neoplasms

Pituitary tumors account for approximately 10-15% of intracranial neoplasms.. Using the cDNA microarray method, we have previously compared expression under two distinct conditions: a pool of 4 clinically non-functioning pituitary adenomas (NFPA) and a spinal cord metastasis of a non-functioning pituitary carcinoma, in order to gain biological insights into genomic changes of pituitary neoplasias. In the present study, we further investigated the mRNA expression of 3 selected genes previously described as being involved in other neoplasias based on a series of 60 pituitary adenomas: CRABP1 (cellular retinoic acid binding protein 1), GRP (gastrin-releasing peptide), and RERG (Ras-related, estrogen- regulated, growth inhibitor).. The expression of CRABP1, GRP, and RERG was determined by quantitative RT-PCR.. A significantly higher content of CRABP1 mRNA was observed in NFPA compared to functioning adenomas, and PRL-secreting adenomas showed a lower expression of this gene compared to normal pituitary. A lower expression of GRP mRNA was detected in NFPA compared to normal pituitary and also to functioning adenomas. RERG mRNA was overexpressed in NFPA in comparison to functioning adenomas and to normal pituitary. Among the functioning adenomas, only the ACTH-secreting adenomas presented a higher expression of RERG mRNA compared to normal pituitary.. The findings of differential expression of CRABP1 in prolactinomas and of RERG in NFPA compared to normal pituitary suggests that retinoic acid and estrogen receptor, respectively, could be involved in the tumorigenesis of these adenomas subtypes. Additional studies are required to further confirm this hypothesis.

Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adolescent; Adult; Aged; Gastrin-Releasing Peptide; Gene Expression; GTP Phosphohydrolases; Humans; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Pituitary Gland; Pituitary Neoplasms; Prolactin; Receptors, Retinoic Acid; RNA, Messenger; Young Adult

The effects of gastrin-releasing peptide (GRP) and vasoactive intestinal polypeptide (VIP) on the prolactin gene transcription of cultured pituitary of male Sprague-Dawley (SD) rats PRL releasing tumor (PPRT) (induced by estradiol) cells were studied. The PRL mRNA levels were determined by in situ hybridization of cytoplasmic RNA with a DIG-labeled PRL cDNA probe. PRL mRNA levels didn't change when the PPRT cells were incubated with 10(-8) mol/L or 10(-7) mol/L GRP for 24 h, but decreased by 20% when GRP was increased to 10(-6) mol/L (P < 0.05). The PRL mRNA level increased to 1.60, 2.10, 2.21 times of the control group when the PPRT cells were respectively incubated with 10(-8), 10(-7), 10(-6) mol/L VIP for 24 h (P < 0.05). The PRL mRNA level didn't change when the PPRT tumor cells were incubated with 10(-8) mol/L E2 for 48 h, but did increase to 2.80 and 2.92 times of the control group respectively when 10(-7) mol/L and 10(-6) mol/L E2 were used. The results above indicated that GRP and VIP exert an inhibitory and a stimulatory effect on RPL gene transcription respectively, while the stimulatory action of E2 on PRL secretion is a direct one.

Topics: Animals; Estradiol; Gastrin-Releasing Peptide; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transcription, Genetic; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

The bombesin-related peptides gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been demonstrated in the anterior pituitary (AP) on an immunological basis. We studied the presence of mRNAs for these peptides and for their receptors by RNAse protection assay using fresh adult male rat AP, AP cell reaggregates cultured in the presence of estradiol and the rat AP derived GH3 cell line. In total RNA from fresh AP we detected high amounts of NMB mRNA and much smaller amounts of GRP mRNA, while finding a weak signal for GRP-receptor (GRP-R) and NMB-receptor (NMB-R) mRNAs. In total RNA from the reaggregate cell cultures we detected high levels of NMB mRNA as well as a strong signal for GRP-R mRNA. Finally, in GH3 cells, high levels of NMB mRNA and GRP-R mRNA were found, while GRP mRNA and NMB-R mRNA remained undetectable even in high amounts (200 micrograms) of total RNA. We conclude that mRNAs encoding both bombesin-related peptides and each of the mRNAs encoding their receptors are expressed in rat AP tissue. NMB mRNA is more prominent than GRP mRNA in all AP-like tissues examined (fresh AP, estradiol-treated reaggregate AP cell cultures and GH3 cells). NMB-R mRNA and GRP-R mRNA are both present in low levels in fresh AP whereas the GRP-R mRNA is predominant in GH3 cells and estradiol treated AP reaggregate cell cultures. Compared to fresh AP tissue, NMB mRNA and GRP-R mRNA expression is enhanced in estradiol-treated reaggregate cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; DNA Probes; Estradiol; Gastrin-Releasing Peptide; Gene Expression Regulation; Male; Neurokinin B; Peptide Biosynthesis; Peptides; Pituitary Gland, Anterior; Pituitary Neoplasms; Rats; Rats, Wistar; Receptors, Bombesin; Ribonucleases; RNA, Messenger; Tumor Cells, Cultured

Neuroendocrine tumours of the lung and gut are known to possess bombesin-like immunoreactivity. The recent observation that gastrin releasing peptide (GRP), a 27 amino acid peptide isolated from the porcine intestine, may be the mammalian analogue of bombesin led us to look for this peptide in a variety of human neoplasms. Formalin-fixed tissues from 85 tumours were examined by the immunoperoxidase technique, using specific antisera to the GRP molecule (1-27) and the GRP fragment (1-16). Intense cytoplasmic GRP immunoreactivity was seen in thyroid medullary carcinomas (3/3), carcinoids of lung, pancreas, and intestine (22/36), and paragangliomas (2/3). Less frequent staining was present in pulmonary small cell (oat cell) carcinomas (1/8) and pituitary adenomas (1/6). Complete absence of immunoreactivity was observed in three phaeochromocytomas, five Merkel cell tumours, six neuroblastomas and 15 non-neuroendocrine tumours. Normal neuroendocrine cells of the thyroid (C-cells) and bronchial mucosa (Kulchitsky cells) exhibited GRP immunoreactivity; nerve fibres from all sites failed to demonstrate staining for GRP. In each positive case, the pattern of staining for GRP (1-27) and GRP (1-16) was identical, although the GRP (1-16) immunostaining was weaker. These findings indicate that bombesin immunoreactivity in human neuroendocrine cells and tumours is attributable to GRP-like molecules and that GRP is a useful marker of neuroendocrine differentiation in many tumours.

Topics: Adenoma; Adrenal Gland Neoplasms; Amino Acid Sequence; Bombesin; Carcinoid Tumor; Carcinoma, Small Cell; Gastrin-Releasing Peptide; Gastrins; Humans; Intestinal Neoplasms; Lung Neoplasms; Neoplasms; Neurosecretory Systems; Pancreatic Neoplasms; Peptides; Pheochromocytoma; Pituitary Neoplasms; Thyroid Neoplasms