The CXCR4 antagonist AMD3100 suppresses hypoxia-mediated growth hormone production in GH3 rat pituitary adenoma cells

Abstract. The effect of corticosterone and dexamethasone on the production of growth hormone and prolactin was studied in rat pituitary tumour cells (GH3-cells) in culture. Corticosterone and dexamethasone caused a dose-dependent stimulation of growth hormone synthesis, and the highest concentration (10−6 mol/l) increased growth hormone levels to 250% of controls. This concentration, however, decreased prolactin synthesis to 25% of the control values. The cytosol fractions from monolayer cultures as well as from tumours of GH3-cells were found to possess receptor molecules for glucocorticoid hormones, having a sedimentation constant close to 8 S in a salt-free buffer and 4 S in the presence of 0.5 mol/l KCL. Isoelectric point of the receptor was 5.8. Scatchard analysis showed one single class of binding sites with high affinity (Kd 2.1 ± 0.4 (sd × 10−9 mol/l). Studies on the steroid specificity revealed that dexamethasone had the highest affinity for the receptor. Corticosterone, cortisol and progesterone had also high affinity, whereas testosterone and oestradiol-17β had no significant affinity for the receptors. After in vivo administration of [3H]dexamethasone to GH3 tumour-bearing rats, radioactivity could be extracted from purified nuclei bound to 4 S macromolecules. The presence of receptors for glucocorticosteroid hormones in the GH3-cells, suggests that these hormones may alter growth hormone and prolactin production at the anterior pituitary level.

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Cell cycle distributions, growth characteristics, and variation in prolactin and growth hormone production in cultured rat pituitary cells

Virchows Archiv B Cell Pathology ◽

10.1007/bf02889131 ◽

1977 ◽

Vol 23 (1) ◽

Author(s):

O. P. F. Clausen ◽

K. M. Gautvik ◽

T. Lindmo

Keyword(s):

Cell Cycle ◽

Growth Hormone ◽

Growth Characteristics ◽

Pituitary Cells ◽

Hormone Production ◽

Rat Pituitary ◽

Rat Pituitary Cells

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PRODUCTION OF BOTH PROLACTIN AND GROWTH HORMONE BY CLONAL STRAINS OF RAT PITUITARY TUMOR CELLS

The Journal of Cell Biology ◽

10.1083/jcb.47.1.61 ◽

1970 ◽

Vol 47 (1) ◽

pp. 61-70 ◽

Cited By ~ 215

Author(s):

Armen H. Tashjian ◽

Frank C. Bancroft ◽

Lawrence Levine

Keyword(s):

Growth Hormone ◽

Mammalian Cells ◽

Cell Protein ◽

Pituitary Cells ◽

Hormone Production ◽

Rat Pituitary ◽

Organ Specific ◽

Cell Strains ◽

Rat Pituitary Tumor Cells ◽

Rat Pituitary Cells

Several established clonal strains of rat pituitary cells which produce growth hormone in culture have been shown to secrete a second protein hormone, prolactin. Prolactin was measured immunologically in culture medium and within cells by complement fixation. Rates of prolactin production varied from 6.6 to 12 µg/mg cell protein per 24 hr in four different cell strains. In these cultures ratios of production of prolactin to growth hormone varied from 1.0 to 4.1. A fifth clonal strain produced growth hormone but no detectable prolactin. Intracellular prolactin was equivalent to the amount secreted into medium in a period of about 1–2 hr. Both cycloheximide and puromycin suppressed prolactin production by at least 94%. Hydrocortisone (3 x 10-6 M), which stimulated the production of growth hormone 4- to 8-fold in most of the cell strains, reduced the rate of prolactin production to less than 25% of that in control cultures. Conversely, addition of simple acid extracts of several tissues, including hypothalamus, to the medium of all strains increased the rate of production of prolactin six to nine times and decreased growth hormone production by about 50%. We conclude that multifunctional rat pituitary cells in culture show unusual promise for further studies of the control of expression of organ-specific activities in mammalian cells.

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