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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of estrogens on the regulation of dopamine receptors in the MtT/W15 transplantable rat pituitary tumor. Diethylstilbestrol (DES) and 17beta-estradiol treatment in female rats significantly decreased the number of dopamine binding sites (B max) from 85 +/- 3.9 fmol/mg protein in untreated rats to 9.2 +/- 1.2 and 8.2 +/- 2.8 fmol/mg protein in DES and 17beta-estradiol-treated rats, respectively, while the binding affinities (Kd) did not change significantly. Testosterone treatment did not change the B max, while ovariectomy resulted in a significant increase in the B max (146.3 +/- 6.7 fmol/mg protein). The effects of DES on the B max were reversible, since removal of the DES for one week before sacrificing the animals led to a marked increase in the B max (54.9 +/- 3.1 fmol/mg protein). Pituitaries from normal female rats treated with DES for 6 and 9 weeks had a significant decrease in the B max. These results show that the number of dopamine binding sites in the membranes of MtT/W15 tumors is decreased by estrogen treatment and that this effect is reversible after removal of the estrogenic stimulus.
Mol Cell Endocrinol 1986 Feb
PMID:Regulation of dopamine receptors in the MtT/W15 transplantable pituitary tumor by estrogen. 394 67

We have characterized the process by which the growth hormone (GH) gene is stimulated in rat pituitary tumor cells (GC or GH3) by the steroid hormone dexamethasone (Dex) and the thyroid hormone, L-triiodothyronine (T3). A primary transcriptional response is detected within 60 minutes of addition of T3 or Dex + T3 to GH-producing cells (GC or GH3). A fivefold transcriptional stimulation of GH nuclear RNA occurs in cells cultured with serum substitute medium and induced with Dex + T3, while T3 alone induces a modest two- to threefold stimulation. The absence of fetal calf serum from the cell culture medium does not decrease the level of transcriptional activity of the GH gene during hormone stimulation. Twenty-four hours after addition of Dex + T3 the cytoplasmic GH mRNA shows a 50-fold increase, as measured by S1 nuclease analysis. This large accumulation of cytoplasmic GH mRNA in contrast to the relatively small changes in GH gene activity is inconsistent with solely a transcriptional mechanism of hormone induction. We suggest that a change in specific GH mRNA stability also takes place in response to Dex + T3. In contrast to other reports, transcriptional stimulation of the GH gene by Dex is insignificant except in the presence of T3.
J Mol Biol 1985 Jan 05
PMID:Regulation of growth hormone messenger RNA synthesis by dexamethasone and triiodothyronine. Transcriptional rate and mRNA stability changes in pituitary tumor cells. 398 36

We studied the in vitro responsiveness of prolactin-secreting MtTW15 and 7315a pituitary tumor cells to stimulation by selected secretagogues using a perifusion technique. Prolactin release by these cells was refractory to thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). In contrast, 50 mM K+, dibutyryl cAMP, theophylline, phospholipase A2 and phorbol myristate acetate all increased prolactin release from both tumor cell types. Phospholipase C increased prolactin release from 7315a but not from MtTW15 cells. TRH increased 32P incorporation into phosphatidylinositol in the 7315a but not in the MtTW15 tumor cells. Therefore, the refractoriness of these tumors to TRH and VIP may be at least partially due to a defect in the receptor or in the process that couples receptor binding and intracellular biochemical processes. In the MtTW15 tumor at least part of the defect may be related to phospholipid hydrolysis.
Mol Cell Endocrinol 1984 Jul
PMID:Prolactin release from MtTW15 and 7315a pituitary tumors is refractory to TRH and VIP stimulation. 608 25

Specific and high affinity binding sites for angiotensin II were demonstrated in the anterior pituitary gland by binding studies with [125I] iodoangiotensin II. The binding properties of the pituitary receptors were similar to those of angiotensin II receptors present in the adrenal gland. The concentration of binding sites in rat anterior pituitary (293 +/- 50 fmoles/mg protein) was less than in the adrenal gland, but was much greater than in smooth muscle. Angiotensin II receptors were identified in the anterior pituitary tissue of mature and immature animals of both sexes, and in species including rat, rabbit and dog. No binding of angiotensin II was detected in posterior pituitary homogenates, or in GH3 pituitary tumor cells. Collagenase-dispersed anterior pituitary cells also contained specific binding sites for angiotensin II, with equilibrium binding constant (Ka) of 3.6 x 10(9) M-1. The presence of specific high-affinity angiotensin II receptor in the anterior pituitary gland provides a mechanism by which angiotensin-like peptides could modulate the process of pituitary hormone secretion.
Mol Cell Endocrinol 1982 Feb
PMID:Characterization of angiotensin II receptors in the anterior pituitary gland. 627 51

The responsiveness of anterior pituitary tumor (GH3) cells to promoters of prolactin secretion and/or synthesis and cyclic AMP accumulation was studied as a function of cellular Ca2+ content. GH3 cells exposed to media containing 1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid were reduced 7-fold in Ca2+ content without loss of viability. Preparations of Ca2+-depleted cells were largely unchanged in cyclic AMP content when challenged by thyrotropin-releasing hormone (TRH), whereas cells which were subsequently restored at optimal Ca2+ (0.5 mM) responded to the hormone with 2- to 3-fold increases in cyclic AMP content. The decreased responsiveness of Ca2+-depleted cells to TRH was not influenced by phosphodiesterase inhibitors, incubation time, or hormone concentration. TRH-dependent cyclic AMP accumulation was markedly potentiated by forskolin in Ca2+-restored, but not in Ca2+-depleted, cell preparations. Forskolin extended the time period during which cyclic AMP accumulated in response to TRH without altering the TRH concentration dependency of the cells. Varying increases in GH3 cyclic AMP content occurred in response to other hormones or agents which enhance prolactin secretion and/or synthesis. In Ca2+-restored cells, cyclic AMP content was increased 2-fold by prostaglandin E1 (PGE1) and epidermal growth factor (EGF), 10- to 15-fold by vasoactive intestinal polypeptide (VIP) and 6-fold by phorbol myristate acetate (PMA); the capacity of Ca2+-depleted cells, however, to accumulate cyclic AMP in response to PGE1, EGF, and VIP was greatly reduced. Accumulation of cyclic AMP following short-term incubations with cholera toxin similarly was dependent on Ca2+. Exposure of GH3 cells preloaded with 45Ca to TRH, PGE1, EGF, PMA, or VIP resulted in losses of cell-associated 45Ca. Pretreatment with these agents resulted in a decreased capacity of the cells to accumulate 45Ca from the extracellular medium. The results of this study support the hypothesis that various putative humoral regulators of prolactin secretion and/or synthesis act on GH3 cells to alter intracellular Ca2+ metabolism which in turn results in an increased cyclic AMP content through stimulation of adenylate cyclase activity.
Mol Pharmacol 1983 Mar
PMID:Regulation of Ca2+-dependent cyclic AMP accumulation and Ca2+ metabolism in intact pituitary tumor cells by modulators of prolactin production. 630 Jun 49

Epidermal growth factor (EGF) regulates hormone synthesis and decreases the growth rate of clonal lines of rat pituitary tumor cells. [125I]iodo-EGF bound to specific receptors on GH4C1 rat pituitary cells with an apparent Kd of 0.34 nM. At 0 degrees C, 84% of specifically bound [125I]iodo-EGF appeared to be on the cell surface, while at 37 degrees C, 84% of bound [125I]iodo-EGF appeared to be internalized and could not be removed by treatment with an acidic high-salt buffer. Internalization of surface-bound [125I]iodo-EGF required 10 min to reach completion and was markedly temperature-dependent. Monodansylcadaverine, bacitracin, ammonium chloride, chloroquine, quinacrine and vinblastin did not inhibit internalization of [125I]iodo-EGF, suggesting that transglutaminase is not involved; but these drugs did cause an increased accumulation of radioactivity, probably by inhibiting degradation. In 2 h at 37 degrees C, approx. 35% of cell-associated [125I]iodo-EGF was degraded as analyzed by gel filtration, and 72% of the material that dissociated from the cells migrated as low molecular weight material or iodo-Tyr. Incubation of GH4C1 cells with unlabeled EGF caused a prolonged and dose-related decrease in the ability of the cells to bind [125I]iodo-EGF in a subsequent incubation, i.e. down-regulation. The pathway for internalization and degradation of the EGF-receptor complex in GH4C1 cells resembles that described for fibroblasts, in which the cellular response is different, but differs from the behavior of other hormone-receptor complexes in GH4C1 pituitary cells.
Mol Cell Endocrinol 1983 Dec
PMID:Binding and internalization of epidermal growth factor by rat pituitary tumor cells. 631 83

GH3 pituitary tumor cells were labeled to isotopic equilibrium with [3H]inositol. Thyrotropin-releasing hormone (TRH), which has been shown to stimulate inositol phospholipid metabolism in these cells, enhanced the accumulation of [3H]inositol-derived radioactivity in the cell's acid-soluble fraction. Separation of the [3H]inositol metabolites by ion-exchange chromatography revealed that TRH induced a rapid rise in the cellular content of [3H]inositol mono-, bis-, and trisphosphate. The latter two metabolites accumulated in a multiphasic manner with an initial peak 5-10 sec after TRH addition. This was followed by a short-lived decline and a secondary rise which left the metabolite levels elevated for at least 50 min. The GH3 cell [3H]inositol monophosphate and [3H] inositol content also rose in response to TRH, but the latter accumulated with a considerably slower time course than the phosphorylated derivatives. None of these responses could be mimicked by the calcium ionophore A23187. Incubation of GH3 cells with TRH in the presence of lithium led to an enhanced accumulation of [3H]inositol monophosphate and, to a lesser extent, of [3H]inositol bis- and trisphosphate. This accumulation rose in a linear fashion with time for at least 20 min, by which point 50% of the [3H]inositol-containing phospholipids had been depleted. When lithium was added 30 min after TRH, [3H]inositol monophosphate accumulated at the same rate as was found when TRH and lithium were added together, indicating that the TRH-induced phospholipid response in GH3 cells does not desensitize. Under normal conditions, approximately equal amounts of the three [3H]inositol phosphates were formed within 5 sec of TRH addition. However, when TRH was added to cells grown chronically in lithium-containing medium, or to cells incubating at a subphysiological temperature (25 degrees), greater than 90% of the metabolites formed were the bis- or trisphosphates. This indicates that the primary event stimulated by TRH is the breakdown by phospholipase C of phosphatidylinositol 4,5-bisphosphate and, perhaps also, of phosphatidylinositol 4-phosphate.
Mol Pharmacol 1984 Mar
PMID:Thyrotropin-releasing hormone-stimulated [3H]inositol metabolism in GH3 pituitary tumor cells. Studies with lithium. 632 43

The effect of steroids on the growth of AtT-20 mouse pituitary tumor cells was investigated. It was found that under certain conditions glucocorticoids inhibit growth. Specificity studies indicated that only glucocorticoids caused this effect. Biopotency studies indicated that dexamethasone had its mid-maximal effect around 5 nM. At least part of this inhibition was caused by a decrease in the cell's ability to synthesize DNA; glucocorticoids inhibit the rate at which tritiated thymidine is incorporated into TCA-precipitable material. The magnitude of the growth-inhibiting effect depended upon the prior culture history of the cell. The effect was least on cells derived from exponentially growing cultures and most effective on cells derived from cultures that were approaching their density limit. It is concluded that glucocorticoids inhibit AtT-20 cell growth by interfering with their ability to transform from confluent cultures to ones that grow exponentially. The significance of this finding is that now two mechanisms must be considered when investigating the pathways through which glucocorticoids decrease the ACTH production of the AtT-20 cell.
Mol Cell Endocrinol 1984 Apr
PMID:Glucocorticoids inhibit the growth of AtT-20 mouse pituitary tumor cells. 632 77

Nuclear [3H]4-OHTAM-ER complexes extracted by 0.6 M KCl from the MCF-7 human breast cancer and the GH3 rat pituitary tumor cell lines, sedimented as a 5S form on sucrose gradients after 1 to 24 h exposure to ligand (20 nM). The nuclear [3H]4-OHTAM-ER from MCF-7 cells increased from 2 +/- 0.2 pmoles/mg DNA at 1 h to approximately 4 +/- 0.1 pmoles/mg DNA at 6 and 24 h. In the GH3 cells the nuclear binding of [3H]4-OHTAM increased rapidly, and there was no significant difference in the receptor levels at 1 and 6 h (10 +/- 1.3 and 8.9 +/- 1.1 pmoles/mg DNA, respectively). At 24 h there was a decrease in [3H]4-OHTAM-ER levels (7.0 +/- 0.2 pmoles/mg DNA); however, this was due primarily to an increase in DNA synthesis, which occurred in these cells by 24 h. It appears that in both cell lines there is no processing of nuclear [3H]4-OHTAM-ER, and it is not associated with changes in sedimentation coefficient of the complex. When both cell lines were incubated with [3H]E2 (20 nM), processing of the nuclear [3H]E2-ER occurred over 6 h. In the MCF-7 cells there was a decrease in receptor content within 6 h from 3.2 +/- 0.2 to 0.9 +/- 0.2 pmoles/mg DNA. The nuclear [3H]E2-ER in the GH3 cells decreased from 7.3 +/- 0.5 to 2.8 +/- 0.3 pmoles/mg DNA. Although these cell lines appeared to process the [3H]E2-ER complex, the nuclear forms of [3H]E2-ER were different.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1984 Jul
PMID:Nuclear [3H]4-hydroxytamoxifen (4-OHTAM)- and [3H]estradiol (E2)-estrogen receptor complexes in the MCF-7 breast cancer and GH3 pituitary tumor cell lines. 646 49

The 235-1 clone was recently derived from the 7315a transplantable pituitary tumor and continues to secrete rat prolactin. The cells have a prominent Golgi apparatus which can be stained immunocytochemically for prolactin, but there were no 600-900 nm granules which are characteristic of normal mammotrophs. In a perfused cell-column apparatus, prolactin release from the clone was unchanged by dopaminergic agonists, thyrotropin-releasing hormone and estradiol but stimulated by dibutyryl cyclic AMP. Cellular cyclic AMP content was also not changed by dopamine but was dramatically enhanced by prostaglandin E1, indicating that at least one hormone-adenylate cyclase coupling mechanism was functional. In radioligand binding studies using the dopamine antagonist [3H]spiperone, no evidence of a dopamine receptor was obtained. The [3H]spiperone binding present was not stereoselective, and exceedingly high concentrations of other ligands were required to displace the binding. In addition, the induction of a prolactin-secreting hard tumor in rats by subcutaneous inoculation of the 235-1 cells failed to induce measurable dopamine receptors associated with the tumor cells. In order to address the possibility that there were functional dopamine receptors on these cells, but that they could not be resolved with either the cell column and cyclic AMP studies or the radioreceptor assay, the clone cells were incubated with 0.1-100 nM bromocriptine for up to 8 days. Bromocriptine had no effect on the growth rate or prolactin secretion of the 235-1 clone but inhibited prolactin release from anterior pituitary cells by over 73% in control studies. We conclude that the 235-1 clone does not express dopamine receptors and that the presence of dopamine receptors is obligatory for the typical inhibitory effects of bromocriptine on prolactin release and pituitary cell growth.
Mol Cell Endocrinol 1982 Oct
PMID:Failure of dopamine and bromocriptine to affect prolactin release and cell growth in the dopamine receptor-deficient 235-1 clone. 712 25


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