Studies on the glucocorticoid-receptor blocking action of RU 38486 in cultured ACTH-secreting human pituitary tumour cells and normal rat pituitary cells

1985 ◽  
Vol 109 (1) ◽  
pp. 64-69 ◽  
Author(s):  
S. W. J. Lamberts ◽  
E. G. Bons ◽  
P. Uitterlinden
Keyword(s):  
Pituitary Tumour ◽  
Tumour Cells ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Inhibiting Effect ◽  
Rat Pituitary ◽  
Normal Rat ◽  
Rat Pituitary Cells ◽  
Acth Secreting ◽  
Acth Release

Abstract. The glucocorticoid-receptor blocking actions of RU 38486, a new compound with anti-progesterone activity, have been investigated in cultured human ACTH-secreting pituitary tumour cells and normal rat pituitary cells. Pre-incubation of human pituitary tumour cells for 24 h with RU 38486 (1 μm) did not influence basal or CRF-stimulated ACTH release. RU 38486 (100 nm–1 μm) significantly overcame or prevented the dexamethasone (100 nm–1 μm)-induced inhibition of CRF-stimulated ACTH release by the cultured tumour cells prepared from 2 patients with Cushing's disease. The tumour cells of a third patient were insensitive to CRF. Pre-incubation for 24 h with 1 μm RU 38486 facilitated CRF-stimulated ACTH release significantly. Studies with cultured normal rat pituitary cells showed that the inhibiting effect of 24 h pre-incubation with 10 and 50 nm dexamethasone on CRF-stimulated ACTH release could be acutely (measured over 4 h) overruled in a dose-dependent way by RU 38486 (100 nm, 1 and 10 μ), while pre-incubation for 24 h of these cells with RU 38486 (100 nm and 1 μm) significantly attenuated the acute inhibiting effect of 1 μm dexamethasone on CRF-stimulated ACTH-release. The results of these in vitro experiments are discussed against the background of the possible therapeutic use RU 38486 in patients with Cushing's syndrome in order to block the deleterious effects of high circulating cortisol concentrations.

scholarly journals Benzene and 2-ethyl-phthalate induce proliferation in normal rat pituitary cells

Pituitary ◽  
2016 ◽  
Vol 20 (3) ◽  
pp. 311-318 ◽  
Author(s):  
Laura Tapella ◽  
Antonella Sesta ◽  
Maria Francesca Cassarino ◽  
Valentina Zunino ◽  
Maria Graziella Catalano ◽  
...  
Keyword(s):  
Pituitary Cells ◽  
Rat Pituitary ◽  
Normal Rat ◽  
Rat Pituitary Cells

Dihydropyridine Ca2+ antagonists: potent inhibitors of secretion from normal and transformed pituitary cells

1985 ◽  
Vol 248 (5) ◽  
pp. C510-C519 ◽  
Author(s):  
J. J. Enyeart ◽  
T. Aizawa ◽  
P. M. Hinkle
Keyword(s):  
Endocrine Cells ◽  
Hormone Secretion ◽  
Prolactin Secretion ◽  
Pituitary Cells ◽  
Excitable Cells ◽  
Rat Pituitary ◽  
Ic50 Values ◽  
Normal Rat ◽  
Rat Pituitary Cells ◽  
Ca2 Channels

Three dihydropyridine (DHP) Ca2+ antagonists were compared with several other organic Ca2+ antagonists with respect to their ability to inhibit depolarization-dependent hormone secretion from the GH4C1 pituitary cell line and from normal rat pituitary cells. The three DHP, nimodipine, nisoldipine, and nifedipine, potently and specifically inhibited KCl-stimulated prolactin secretion from GH4C1 cells (estimated IC50 values: 1.8, 1.8, and 6.0 nM, respectively). Both basal and thyrotropin-releasing hormone-stimulated secretion from GH4C1 cells were much less sensitive to inhibition by the DHP. The inhibition by the DHP was reversible, and their potency was independent of depolarizing concentrations of KCl between 18.8 and 53.8 mM. Other organic antagonists, including verapamil, cinnarizine, and diltiazem, blocked secretion from GH4C1 cells but at much higher concentrations. The estimated IC50 values for these three were 1,000, 1,100, and 3,500 nM, respectively. Depolarization-stimulated prolactin secretion from normal pituitaries was inhibited by the DHP and verapamil at the same concentrations found effective in GH4C1 cells. KCl-stimulated 45Ca2+ uptake by GH4C1 cells was also blocked by DHP at concentrations that inhibited secretion. Since depolarization-stimulated secretion and 45Ca2+ uptake are probably triggered by Ca2+ entering through voltage-sensitive channels, the above results suggest that DHP antagonists potently block these channels in both normal and transformed pituitary cells. These Ca2+ channels appear to be identical in this respect. These findings further suggest a similarity between the Ca2+ channels of endocrine cells and those of smooth muscle and other excitable cells.

Flunarizine, a calcium influx blocker, inhibits TRH- but not potassium-stimulated prolactin secretion

1984 ◽  
Vol 107 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Janet E. Merritt ◽  
Stephen Tomlinson ◽  
Barry L. Brown
Keyword(s):  
Calcium Influx ◽  
Prolactin Secretion ◽  
Pituitary Cells ◽  
Monolayer Cultures ◽  
High K ◽  
Rat Pituitary ◽  
Normal Rat ◽  
Rat Pituitary Cells

Abstract. The effect of flunarizine on the secretion of prolactin from monolayer cultures of normal rat pituitary cells has been determined. Both basal and TRHstimulated secretion were found to be significantly inhibited by micromolar concentrations of flunarizine, whereas depolarization (high K+)-stimulated secretion was virtually unaffected. These results indicate that TRH-stimulated prolactin secretion probably involves calcium influx and that flunarizine may be useful as a probe for particular Ca2+ channels.

Interaction between insulin and thyroid hormone in rat pituitary tumour cells: insulin attenuates tri-iodothyronine-induced growth hormone mRNA levels

1993 ◽  
Vol 137 (1) ◽  
pp. 107-114 ◽  
Author(s):  
D. Prager ◽  
M. M. Weber ◽  
S. Gebremedhin ◽  
S. Melmed
Keyword(s):  
Protein Synthesis ◽  
Insulin Treatment ◽  
De Novo ◽  
Pituitary Tumour ◽  
Tumour Cells ◽  
Transcriptional Level ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Insulin Effect ◽  
Rat Pituitary

ABSTRACT Insulin has previously been shown to inhibit basal and stimulated rat GH (rGH) secretion as well as basal GH transcription in rat pituitary cells. The effect of physiological doses of insulin on tri-iodothyronine (T3)-stimulated GH mRNA levels in rat pituitary tumour cells was therefore examined. Insulin (7 nmol/l) suppressed T3-stimulated GH mRNA levels in GC and GH3 rat pituitary tumour cells by 58%. This inhibitory effect of insulin on T3-stimulated GH mRNA levels was already present after 24 h of treatment, and persisted for at least 48 h after insulin treatment was withdrawn. The effect of insulin on GH mRNA was selective, as rat prolactin mRNA was stimulated by insulin and T3 in the same cells. Treatment of cells with cycloheximide (10 μmol/l) did not alter the attenuation of GH mRNA levels by insulin, indicating that the insulin effect is independent of new protein synthesis. When de-novo mRNA synthesis was blocked with actinomycin D (4 μg/ml) for up to 7 h, an additional decrease in the relative amount of GH mRNA levels was observed after 24, 48 and 72 h of insulin treatment, indicating that an effect of insulin on GH mRNA stability is likely. The results show that physiological doses of insulin selectively attenuate the stimulatory effect of T3 on GH mRNA levels. This suppressive effect of insulin occurs independently of protein synthesis and is presumably mediated both at a transcriptional and post-transcriptional level. Journal of Endocrinology (1993) 137, 107–114

GROWTH IN MONOLAYER CULTURE OF RAT PITUITARY CELLS WHICH SYNTHETIZE AND RELEASE ACTH

1975 ◽  
Vol 79 (3) ◽  
pp. 421-430 ◽  
Author(s):  
R. E. Lang ◽  
I. Hilwig ◽  
K. H. Voigt ◽  
H. L. Fehm ◽  
E. F. Pfeiffer
Keyword(s):  
Pituitary Gland ◽  
Monolayer Culture ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Antibody Technique ◽  
Gland Cells ◽  
Rat Pituitary ◽  
Rat Pituitary Cells ◽  
Dose Dependent ◽  
Acth Release

ABSTRACT Cultures of rat pituitary gland cells were developed to study biosynthesis and release of ACTH. ACTH measurement was accomplished by radioimmunoassay. ACTH release was observed following stimulation with theophylline and cAMP in a dose-dependent manner. Biosynthesis was demonstrated by incorporation of 3H-phenylalanine into the hormone, employing a double antibody technique.

Ultrastructural distribution of growth hormone and prolactin mRNAs in normal rat pituitary cells: a comparison between preembedding and postembedding methods

1994 ◽  
Vol 102 (4) ◽  
pp. 265-270 ◽  
Author(s):  
A. Matsuno ◽  
T. Kirino ◽  
Y. Ohsugi ◽  
H. Utsunomiya ◽  
S. Takekoshi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pituitary Cells ◽  
Rat Pituitary ◽  
Normal Rat ◽  
Rat Pituitary Cells

Signal transduction alterations in GH12C1 rat pituitary tumour cells following treatment with 5-azacytidine

1991 ◽  
Vol 6 (3) ◽  
pp. 257-268
Author(s):  
V. C. Parrow ◽  
J. O. Gordeladze ◽  
E. J. Paulssen ◽  
P. Aleström ◽  
K. M. Gautvik
Keyword(s):  
Drug Treatment ◽  
Adenylyl Cyclase ◽  
Cholera Toxin ◽  
Pertussis Toxin ◽  
Pituitary Tumour ◽  
Tumour Cells ◽  
Temporary Increase ◽  
Pituitary Cells ◽  
Intact Cells ◽  
Rat Pituitary

ABSTRACT In GH12C1 rat pituitary cells treated with 5-azacytidine, the stimulatory effects exerted by vasoactive intestinal peptide (VIP), the GTP analogue guanyl-5′-yl imidodiphosphate (Gpp(NH)p), 12-O-tetradecanoyl phorbol 13-acetate, cholera toxin and pertussis toxin on the membrane-bound adenylyl cyclase were almost completely abolished. The corresponding inhibitory effect of somatostatin was increased. Alterations in adenylyl cyclase responsiveness began at the end of the drug treatment, and were most pronounced on day 5 after removal of 5-azacytidine. The cells subsequently and completely recovered after 10 days in the absence of the drug. Measurements of cholera toxin- and VIP-enhanced cyclic AMP levels in intact cells confirmed these results, and VIP appeared to have no stimulatory effect on GH secretion after 5-azacytidine treatment. Down-regulation of Gαs RNA also occurred on day 5 after cessation of drug treatment. ADP-ribosylation subsequent to stimulation with pertussis toxin was markedly increased, indicating an enhancement of Gαi and/or GGαo. Furthermore, both basal and Gpp(NH)p-stimulated phospholipase C activities were augmented by pre-exposure to 5-azacytidine. Treatment of GH12C1 rat pituitary tumour cells with 5-azacytidine therefore causes a marked but temporary increase in the ratio of Gαi/Gαs protein levels.

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