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

To understand how estradiol-17 beta (E2) influences MtTW15 rat pituitary tumor function, we have evaluated the cytosolic E2 binding properties of tumors derived from control and steroid treated host animals. Specific E2 binding (approximately 3 pmoles/g tumor) was observed in all groups and was steroid responsive. The E2 binding macromolecule migrated to 7S following sucrose density gradient sedimentation and was specific for estrogenic steroids. Saturation analysis of E2 binding revealed a high affinity interaction (Kd = 5.5 +/- 0.5 x 10(-10) M). Furthermore, E2 binding was temperature-sensitive and degraded by trypsin. Thus, the MtTW15 tumor contains an estrogen receptor. Accordingly, the effects of 4 antiestrogenic drugs on tumor estrogen-receptor levels, tumor growth and hormone production were evaluated. In general, these drugs reduced cytosolic estrogen receptor levels, promoted tumor growth and increased tumor growth-hormone production. It is suggested that these compounds can exert both estrogen agonist and antagonist properties in MtTW15 tumors.
Mol Cell Endocrinol 1981 Sep
PMID:Estrogen receptor-like macromolecule in MtTW15 rat pituitary tumors: effects of antiestrogens. 728 85

TRH is known to stimulate the transcription of the TSH gene in pituitary cells. To examine TRH-responsive elements of the human TSH alpha-subunit gene, we have used transient transfection of GH3 rat pituitary tumor cells. Using this system, TRH treatment stimulated expression of a reporter gene containing 846 base pairs from the 5'-flanking region of the human glycoprotein hormone alpha-subunit gene linked to luciferase. Analysis of 5'-deletions of the alpha-subunit sequence revealed that at least two DNA regions with upstream limits between positions -223 to -190 and positions -151 to -135 are important for regulation by TRH. The more proximal region includes a previously defined cAMP-response element (CRE) while the more upstream region contains an element with sequence similarity to the binding site for the pituitary transcription factor, Pit-1. The TRH responsiveness of each individual region was tested by inserting fragments upstream of a thymidine kinase-luciferase reporter gene. The -151 to -100 region had basal enhancer activity and permitted a 3.4-fold response to TRH. The -223 to -168 region did not permit a TRH response, but possessed basal enhancer activity. The combination of both regions resulted in a 5-fold stimulation by TRH. To assess the contributions of different signal transduction pathways, various combinations of treatments were examined. Combined treatment with TRH and forskolin led to an additive activity. Treatment with TRH plus phorbol 12-myristate-13-acetate resulted in the same level of reporter gene activity as with either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1994 Apr
PMID:Involvement of a cAMP-responsive DNA element in mediating TRH responsiveness of the human thyrotropin alpha-subunit gene. 751 24

In the present report, we have investigated the role of DNA methylation on the binding and trans-acting properties of transcription factors involved in the regulation of the rat prolactin (rPRL) gene, specifically Pit-1. To this aim we took advantage of a model system composed of three GH3 rat pituitary tumor cell lines that greatly differed in the extent of rPRL gene methylation and in the level of rPRL gene expression. Northern blot analyses indicated that identical species of Pit-1 mRNA were present to similar extent in the three GH3 cell lines. Electrophoretic mobility shift assays further demonstrated that Pit-1 was present in nuclear extracts and displayed equal affinities to bind the 1P responsive element encompassing the -65 to -38 region of the rPRL promoter, whatever the GH3 cell line tested. These data suggested that differential expression of the rPRL gene among cell lines did not result from variable amounts of Pit-1. By combining in vitro methylation and transient transfection experiments with a rPRL promoter-driven CAT construct, we showed that extensive methylation at CpG sites abolished the expression of the reporter gene. Furthermore, in vivo competition assays demonstrated that CpG methylation inhibited gene expression by preventing the binding of transcription factors We propose that related mechanisms linked to DNA methylation might alter the activity of the endogenous PRL gene in the low expressing cell line.
Mol Cell Endocrinol 1995 Feb 27
PMID:CpG methylation represses the activity of the rat prolactin promoter in rat GH3 pituitary cell lines. 753 57

Insulin and cAMP stimulate prolactin gene transcription and prolactin-CAT expression in rat pituitary tumor GH cells. Expression of prolactin-CAT construct, pPrl(-173/+75)CAT, is stimulated 10- to 30-fold by either insulin or cAMP. Addition of both insulin and cAMP resulted in an additive 20- to 60-fold stimulation. Although the regulatory sequences have not been defined precisely, both insulin and cAMP appear to stimulate transcription of prolactin-CAT expression through possibly identical sequences in the -106/-87 region of the promoter. Insulin mediated increases in prolactin-CAT expression are not ras-dependent in GH4 cells. Thus, a number of experiments were performed to determine that the effects of insulin and cAMP are independent. First, insulin does not stimulate cAMP levels in GH4 cells. Second, cAMP action was inhibited by expression of a mutant regulatory subunit of cAMP-dependent protein kinase A that does not bind cAMP and by expression of an inhibitor of cAMP-dependent protein kinase A, while insulin action was not affected by expression of these proteins. Thus, although the regulatory sequences for insulin and cAMP may be identical, the effects of insulin and cAMP on the prolactin gene are clearly mediated through distinct response pathway.
Mol Cell Endocrinol 1995 Apr 01
PMID:Insulin and cyclic adenosine monophosphate increase prolactin gene expression through different response pathways. 766 80

We showed that the proliferation of F4Z2 cells, established from a rat pituitary tumor, was stimulated by L-triiodothyronine (LT3) in the presence of 3 or 0.1% charcoal treated-fetal calf serum (CT-FCS), and by estradiol (E2) in the presence of 3% CT-FCS only (Cancer Res., 50, 1990, 3786). Here we report on the consequences of the simultaneous addition of these hormones. In the presence of 0.1% CT-FCS, E2, and with a lower potency, estrone and estriol inhibited dose-dependently stimulation by LT3. The results were more complex with 3% CT-FCS: the LT3 effect was blunted by E2 > 0.1 nM (and vice versa) and the hormone effects were additive at lower concentrations. E2, at concentrations antagonistic to the effects of LT3, decreased LT3 binding and LT3 receptor mRNA without modifying the effect of LT3 on these mRNAs. In addition, E2 blocked both the LT3-induced increases of insulin-like growth factor-I (IGF-I) secretion and IGF-I mRNA concentration, and the LT3-induced decrease of IGF-binding proteins in conditioned culture medium. We propose that E2 prevents LT3 stimulation of F4Z2 cell proliferation by blunting the LT3-induced accumulation of unbound IGF-I in the culture medium.
J Steroid Biochem Mol Biol 1993 Apr
PMID:Interference between estradiol and L-triiodothyronine in the control of the proliferation of a pituitary tumor cell line. 768 2

It is well known that dopamine (DA) inhibits while vasoactive intestinal peptide (VIP) and angiotensin II (ANG II) stimulate prolactin (PRL) release from normal anterior pituitary lactotrophs; however, elucidation of the intracellular mechanisms involved in these effects has been hindered by the cellular heterogeneity of the anterior pituitary. MMQ cells, isolated from the PRL-secreting rat pituitary tumor 7315a is an interesting model since they only secrete PRL. In order to determine whether and which GTP-binding (G) proteins are involved in the modulation of cyclic 3',5'-adenosine monophosphate (cAMP) accumulation and phospholipids turnover and eventually PRL release, we have performed studies with MMQ cells. For this purpose, the levels of various G proteins (alpha o, alpha s, alpha i, alpha q and beta) and their mRNAs, measured by Western and Northern blots respectively, were correlated with intracellular cAMP accumulation in response to DA, VIP or DA plus VIP, and with inositol phosphates (IPx) formation in response to ANG II, DA or DA plus ANG II. This study shows that, when compared to normal pituitary tissue, the levels of alpha o, alpha o2 and alpha i3 were significantly decreased in MMQ cells; those of alpha o1, alpha i (alpha i1 + alpha i2), alpha s42 and alpha q were very low or undetectable while those of alpha s47 and beta were normal. DA was unable to inhibit basal PRL release and cAMP accumulation. VIP increased both cAMP accumulation and PRL release, while cAMP accumulation elicited by VIP could be suppressed by DA. BAY K 8644-induced PRL release also could be suppressed by DA.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 Jun
PMID:MMQ cells: a model for evaluating the role of G proteins in the modulation of prolactin release. 768 3

Blocking K+ channels induces hormone secretion in various pituitary cell lines by a mechanism which is not completely delineated. In the present study, we employed the mouse pituitary tumor-derived AtT-20 cell as a model to evaluate this phenomenon. We correlated the effect of the K+ channel-blocker, tetraethylammonium (TEA), on K+ current and membrane potential utilizing whole cell recording, on cytosol Ca2+ ([Ca2+]i) concentration utilizing fura-2, and on ACTH secretion utilizing a perifusion system. TEA inhibited voltage-dependent K+ current and initiated membrane depolarization in a dose-dependent fashion. Divergences in the sensitivity to TEA between voltage-dependent K+ currents and membrane depolarization indicate that voltage-dependent K+ channels are not responsible for TEA-induced depolarization TEA (1-30 mM) also induced a concentration-dependent rise in [Ca2+]i concentration and ACTH secretion, both of which were inhibited by removing medium Ca2+. Our data indicate that TEA inhibits K+ currents and induces membrane depolarization; this opens Ca2+ channels in the plasmalemma, causing a rise in [Ca2+]i which initiates ACTH secretion. Alteration of K+ channel permeability by hormones or neurotransmitters may thus play an important regulatory role in controlling pituitary hormone secretion.
Mol Cell Endocrinol 1995 Mar
PMID:Blocking K+ channels with TEA induces plasmalemma depolarization, increased [Ca2+]i, and ACTH secretion in AtT-20 cells. 778 10

Autologous regulation of steroid receptors by their cognate ligands has been demonstrated for a number of nuclear receptor family members. To determine the molecular mechanism for glucocorticoid receptor (GR) autoregulation, the expression of glucocorticoid receptor mRNA and protein levels were examined in the mouse AtT-20 pituitary tumor cell line. The expression of c-jun and c-fos mRNA and protein was also examined in the same cell extracts. A rapid down-regulation of the GR protein was observed after treatment with the glucocorticoid analog, triamcinolone acetonide (TA). An oscillatory, parallel regulation of both GR and c-jun mRNA levels occurred. In contrast, POMC mRNA levels remained at a stable, low level during chronic TA treatment. Dose-response analyses also revealed a coordinate down-regulation of GR and c-jun (but not POMC or c-fos) mRNA levels. FOS protein levels were unaffected by TA treatment. Surprisingly, JUN protein levels were increased by TA, even when the c-jun mRNA levels were decreasing. Perhaps a derepression of c-jun mRNA translation occurs after TA treatment, and this may be due to GR/JUN heteromer formation interfering with JUN repression of c-jun mRNA translation. The effect of TA on GR and c-jun gene expression was a primary effect, as it occurred rapidly and was not inhibited by cycloheximide (CHX). Nuclear run-on transcription assays revealed a rapid (15 min) down-regulation in both GR and c-jun gene transcription rates, while POMC gene transcription was unaffected at this early time. Treatment of AtT-20 cells with all-trans retinoic acid gave different kinetics for GR and c-jun mRNA regulation than obtained with TA; however, the GR and c-jun mRNA levels were still coordinately regulated after retinoic acid treatment. Based upon these data, the promoter structures of the GR and c-jun genes, and previously published results, a novel mechanism for the coupled regulation of GR and c-jun transcription, via a direct transcriptional interference with AP-1 (FOS/JUN) activity, is proposed.
Mol Endocrinol 1994 Oct
PMID:Coordinate regulation of glucocorticoid receptor and c-jun mRNA levels: evidence for cross-talk between two signaling pathways' at the transcriptional level. 785 51

We have generated transgenic mice that express the simian virus 40 (SV40) large T antigen under the control of a 1109 bp 5'-flanking sequence of the human thyrotropin beta-subunit (TSH beta) gene. The hybrid gene, termed TTP-1, was microinjected into fertilized mouse eggs and 11 transgenic mice were obtained. One of the transgenic mice, a female, a phenotypical dwarf, developed a pituitary tumor and wasted away from 7 to 9 weeks after birth. To establish the transgenic mouse line, her ovaries were transferred to a normal female, whose ovaries were removed beforehand. To examine the tissue specificity of transgene expression, mRNA of SV40 large T antigen was monitored in various tissues from the transgenic mice by the reverse transcriptase-polymerase chain reaction analysis, and was detected only in the pituitary. Histological and immunohistochemical analyses showed that the pituitary tumors of the transgenic mice were composed of poorly differentiated pituitary cells expressing SV40 large T antigen. These results indicated that the 1109 bp sequence of the human TSH beta 5'-flanking region is essential for pituitary-specific expression of SV40 large T antigen in transgenic mice, which exhibited a dwarf phenotype and developed pituitary tumors. The tumors were composed of undifferentiated cells and did not produce thyrotropin. These transgenic mice should provide a valuable animal model for studying the pathogenesis of anterior pituitary tumors.
Mol Cell Endocrinol 1994 Nov
PMID:Targeted pituitary tumorigenesis using the human thyrotropin beta-subunit chain promoter in transgenic mice. 785 21

Using a combination of polymerase chain reaction and genomic library screening we have cloned a human gene for a subtype of the somatostatin (SST) receptor (SSTR) termed human SSTR5 (hSSTR5), which is located on chromosome 16. The predicted amino acid sequence of hSSTR5 displays 75% sequence identity with a recently identified rat SSTR [Mol. Pharmacol. 42:939-946 (1992)], suggesting that it is the human homologue of this receptor. hSSTR5 consists of a 363-residue polypeptide exhibiting a putative seven-transmembrane domain topology typical of G protein-coupled receptors. The receptor displays considerable sequence identity to hSSTR1 (42%), hSSTR2 (48%), hSSTR3 (47%), and hSSTR4 (46%). Membranes prepared from COS-7 cells transiently expressing the hSSTR5 gene bound 125I-Leu8,D-Trp22,Tyr25-SST-28 (125I-LTT-SST-28) with high affinity and in a saturable manner. SST-14, SST-28, and various synthetic SST peptide agonists produced dose-dependent inhibition of radioligand binding with the following rank order of potency: LTT-SST-28 > SST-28 > D-Trp8-SST-14 > SST-14 approximately RC-160 approximately BIM 23014 > MK-678 > SMS 201-995. hSSTR5 bound SST-28 with a 12.6-fold greater affinity (Ki = 0.19 nM), compared with SST-14 (Ki = 2.24 nM), indicating that the receptor is SST-28 selective. Addition of GTP, guanosine-5'-O-(3-thio)triphosphate, Na+ ions, or pertusis toxin greatly reduced 125I-LTT-SST-28 binding, thereby indicating that hSSTR5 is coupled to pertussis toxin-sensitive G proteins. Both SST-14 and SST-28 displayed dose-dependent inhibition of forskolin-stimulated cAMP accumulation, consistent with functional coupling of the receptor to adenylyl cyclase inhibition. Northern blot analysis of SSTR5 mRNA revealed a 2.4-kilobase transcript in normal rat pituitary and GH3 rat pituitary tumor cells and a 4.0-kilobase transcript in normal human pituitary. Reverse transcriptase polymerase chain reaction revealed expression of the hSSTR gene in fetal human pituitary and hypothalamus but not in human cerebral cortex. In situ hybridization of the rat pituitary showed that SSTR5 mRNA is selectively localized in the anterior lobe. SSTR5 mRNA was not expressed in four human pituitary tumors (somatotroph adenoma, prolactinoma, and chromophobe adenomas) or in a human insulinoma. Although hSSTR5 displays approximately 75% sequence identity with rat SSTR5, the two receptors display significantly different pharmacological profiles, especially with respect to their binding affinities for the SST analogue SMS 201-995.
Mol Pharmacol 1994 Mar
PMID:Molecular cloning, functional characterization, and chromosomal localization of a human somatostatin receptor (somatostatin receptor type 5) with preferential affinity for somatostatin-28. 790 5


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