Growth Hormone-producing Tumor Research Articles

Hepatocyte insulin binding and action in rats with somatomammotrophic tumours.

The effects of chronic elevations of growth hormone levels on hepatic insulin binding and action were studied in rats with subcutaneously implanted growth hormone-producing tumours. These animals were significantly heavier (p less than 0.001; 388 +/- 29 versus 239 +/- 4 g), had elevated insulin levels, (6.8 +/- 0.6 versus 3.3 +/- 0.5 ng/ml), lower glucose concentrations (6.0 +/- 0.4 versus 9.3 +/- 0.5 mmol/l) and larger hepatocyte diameters (28.7 +/- 0.6 versus 24.0 +/- 0.4 micron) and surface areas (2661 +/- 119 versus 1835 +/- 65 micron2) than control rats. Insulin binding and action [net (C14)-glucose incorporation into glycogen] were compared in hepatocytes isolated from these two groups. Because of the difference in hepatocyte size, insulin binding was normalized for cell surface area. Binding of the tracer alone (0.9 +/- 0.05 versus 1.3 +/- 0.12%/cm2) and capacity of the high affinity, low capacity receptor (30.9 +/- 5.9 versus 65.2 +/- 5.9 sites/micron2) were significantly decreased (p less than 0.02) in tumour-bearing rats. Dose-response curves of insulin action in hepatocytes chronically exposed to excess growth hormone were shifted to the right. The maximal response was also significantly decreased. However, the relation between the amount of insulin bound and the proportion of the maximum insulin effect obtained were similar in cells from the two groups. Thus, in rat hepatocytes chronically exposed to excess growth hormone, both a receptor and a post-receptor defect occur while the insulin receptor itself functions normally.

Progestin receptors in prolactin and growth hormone producing tumours in rats.

Progesterone and corticosterone have a similar effect on the production of growth hormone (GH) and prolactin (Prl) by pituitary tumour cells (GH3 cells) in culture. Previously we have shown that progesterone has a high affinity for the glucocorticoid receptors in these cells. Progesterone may therefore exert its effects through binding to the glucocorticoid receptor. The aim of the present study was to investigate if the GH3 tumour cells and an oestrogen induced pituitary tumours, which also produce GH and Prl, possess specific receptors for progesterone. Both the GH3 tumours and the oestrogen induced pituitary tumour were in fact found to possess cytoplasmatic receptor molecules for progesterone by using the potent progestin R5020 as a marker. Isoelectric focusing revealed one binding component (pH 5.9), which was of protein nature. The binding was of high affinity (KD 2 X 10(-9) mol/l). In the oestrogen induced tumour, the maximal binding was 70 fmol/mg cytosol protein. In female rats with GH3 tumours the binding was 55 fmol/mg cytosol protein. Priming of the animals with 1 mg oestradiol-valerate increased the binding to 116 fmol/mg cytosol protein, whereas very little binding was found in GH3 tumours from rats castrated 7 days before sacrifice. The receptors in the oestrogen induced pituitary tumour and the GH3 tumours exhibited high affinity for R5020 and progesterone, whereas corticosterone had no significant affinity for the receptors. Using exchange assay, it was demonstrated that the cytoplasmic progestin receptors could be translocated to the nucleus after administration of progesterone to the animals. Thus, the presence of specific progesterone receptors, different from the glucocorticoid receptors, strongly indicates that athe effects of progesterone on GH and Prl production are mediated through the progesterone receptors.

Structural Changes in Human Pituitary Tumor after Bromocriptine Therapy

The histological appearance of a prolactin-producing tumor and of a growth hormone-producing tumor after short term bromocriptine therapy was studied in detail using light microscopy with conventional and immunocytochemical methods and using transmission electron microscopy. The findings were correlated with clinical, radiological, and biochemical data. Histological changes consisting of clumping of nuclear chromatin and a marked reduction in cytoplasmic volume due to loss of ribosomes, rough endoplasmic reticulum, and Golgi complexes were observed only in the prolactin-producing tumor. Normalization of elevated serum prolactin levels and reduction in size of the tumor observed in serial computed tomograms correlated with striking histological changes found in the tumor. These changes were interpreted to represent a reversible inhibition of the protein-synthetic machinery of the neoplastic cell. Comparable clinical, biochemical, radiological, or structural changes were not observed in the growth hormone-secreting tumor.

Ultrastructural study of the testicular interstitial cells and the prostate involution in rats bearing a transplantable prolactin and growth hormone-producing tumor

The sequential ultrastructural changes of the Leydig cells and the ventral prostatic epithelium were studied in rats bearing a transplantable prolactine and growth hormone-producing tumor. Concomitant measurements of tumor growth and serum hormone levels were also performed. At an early stage of tumor development, simultaneous with significantly elevated serum levels of prolactin and growth hormone and decreased level of testosterone, the Leydig cells exhibited a marked regression, with an almost complete disappearance of the smooth ER. The epithelium of the ventral prostate showed gradual involutionary changes. A general reduction of the RER, Golgi apparatus, and cytoplasmic mass occurred concurrently with an increase in the size and amount of secondary lysosomes and the appearance of giant autophagic vacuoles. Extrusion of cell organelles and cytoplasm portions and the elimination of whole cells into the alveolus lumen were also observed. In rats bearing the largest tumor, the prostate appeared severely regressed. The cells were flattened, the protein-synthetizing system was completely involuted, and the secretion granules were totally absent. Residual bodies occupied the largest part of such cells. Changes in the distribution and intensity of acid phosphatase activity were correlated with epithelium involution.

Ultrastructural changes in B cells of pancreatic islets from rats with elevated levels of circulating growth hormone secreted by MtT-W15 tumor.

The pancreatic B cells from rats bearing a growth hormone-producing tumor (MtT-W15) were studied by electron microscopy before and after incubation in media containing alternatively low (60 mg./100 ml.) and high (300 mg./ 100 ml.) glucose concentrations. Tumor-bearing rats had been previously shown to have increased blood levels of somatotrophin and insulin and also to have B cells with increased responsiveness to in vitro glucose stimulation. B cells from tumor-bearing rats, when compared with controls, showed (1) an increased number of secretory granules, (2) a marked increase in the proportion of pale to dark granules (30 to 60 per cent, as compared with 5 to 25 per cent for controls), and (3) the presence of numerous dilated cisternae of rough endoplasmic reticulum containing a flocculent material resembling the core of the pale granules. The last observation may indicate that pale secretory granules are formed in the endoplasmic reticulum of these hyperactive B cells. The fact that the hyperfunctioning B cells present in tumor-bearing rats possess a high number of pale granules suggests that these granules participate in the processes of insulin synthesis, storage, and secretion. Pancreatic islets from control and tumor-bearing rats alternatively incubated in media with low and high glucose concentrations did not reveal significant morphological changes when compared with the nonincubated islets from the same animals. The extent of degeneration and necrosis observed in some B cells from control and tumor-bearing animals after incubation were unrelated to the glucose concentration in the incubation media.