An acute release of Ca2+ from sequestered intracellular pools is not the primary transduction mechanism causing the initial burst of PRL and TSH secretion induced by TRH in normal rat pituitary cells

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.

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

Acta Endocrinologica ◽

10.1530/acta.0.1070031 ◽

1984 ◽

Vol 107 (1) ◽

pp. 31-35 ◽

Cited By ~ 4

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.

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Steroid receptors in primary cultures of normal rat pituitary cells

Journal of Steroid Biochemistry ◽

10.1016/0022-4731(86)90556-x ◽

1986 ◽

Vol 25 ◽

pp. 34

Author(s):

E Saint Dizier ◽

M.L. Thieulant

Keyword(s):

Steroid Receptors ◽

Primary Cultures ◽

Pituitary Cells ◽

Rat Pituitary ◽

Normal Rat ◽

Rat Pituitary Cells

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

Histochemistry ◽

10.1007/bf00269162 ◽

1994 ◽

Vol 102 (4) ◽

pp. 265-270 ◽

Cited By ~ 10

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

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

Acta Endocrinologica ◽

10.1530/acta.0.1090064 ◽

1985 ◽

Vol 109 (1) ◽

pp. 64-69 ◽

Cited By ~ 19

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.

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Effects of tri-iodothyronine, cortisol and transcriptional inhibitors on vitamin D3-enhanced thyrotrophin secretion by rat pituitary cells in vitro

Journal of Endocrinology ◽

10.1677/joe.0.1210451 ◽

1989 ◽

Vol 121 (3) ◽

pp. 451-458 ◽

Cited By ~ 3

Author(s):

M. C. d'Emden ◽

J. D. Wark

Keyword(s):

Primary Cultures ◽

Relative Increase ◽

Pituitary Cells ◽

Dihydroxyvitamin D ◽

Rat Pituitary ◽

Tsh Secretion ◽

Dependent Inhibition ◽

Rat Pituitary Cells

ABSTRACT The hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to selectively enhance agonist-induced TSH release in the rat thyrotroph in vitro. The interaction of 1,25-(OH)2D3 with tri-iodothyronine (T3) and cortisol was studied in primary cultures of dispersed anterior pituitary cells. TRH (1 nmol/l)-induced TSH release over 1 h was enhanced by 70% (P<0·01) following exposure to 10 nmol 1,25-(OH)2D3/l for 24 h. Pretreatment with T3 (1 pmol/l–1 μmol/l) for 24 h caused a dose-dependent inhibition of TRH-induced TSH release. Net TRH-induced TSH release was inhibited by 85% at T3 concentrations of 3 nmol/l or greater. Co-incubation with 1,25-(OH)2D3 resulted in enhanced TRH-induced TSH release at all T3 concentrations tested (P<0·001). The increment of TRH-induced TSH release resulting from 1,25-(OH)2D3 pretreatment was equivalent in the presence or absence of maximal inhibitory T3 concentrations. At 1 nmol T3/1, there was a two- to threefold relative increase in 1,25-(OH)2D3-enhanced TRH-induced TSH release. Incubation with cortisol (100 pmol/l–100 nmol/l) had no effect on basal or TRH-induced TSH release, nor did it alter 1,25-(OH)2D3-enhanced TRH-induced TSH release when added 24 h before, or at the time of addition of 1,25-(OH)2D3. Actinomycin D and α-amanitin abolished 1,25-(OH)2D3-enhanced TSH secretion. These data demonstrate that the action of 1,25-(OH)2D3 in the thyrotroph required new RNA transcription, and was not affected by cortisol. In the presence of T3, the response of the thyrotroph to TRH induced by 1,25-(OH)2D3 was increased. We have shown that 1,25-(OH)2D3 has significant effects on the action of TRH and T3 in vitro. These findings support the proposal that 1,25-(OH)2D3 may modulate TSH secretion in vivo. Journal of Endocrinology (1989) 121, 451–458

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