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

Growth hormone-releasing hormone (GHRH) and the phorbol ester tetradecanoylphorbol acetate (TPA) each stimulated a rapid and extensive (up to 15-fold) increase in the secretion of growth hormone from cultured ovine anterior pituitary cells. Effects of the releasing hormone on growth hormone secretion were associated with a concurrent, large increase in cellular cyclic AMP accumulation. TPA induced a much smaller (26-78%), though still significant, increase in cellular cyclic AMP levels. Forskolin and isobutylmethylxanthine (IBMX) also stimulated growth hormone secretion and cyclic AMP accumulation. When combined with a maximally effective concentration of GHRH these compounds did not further elevate growth hormone secretion even though they induced further increases in cyclic AMP concentration; this is consistent with activation occurring via a common cyclic AMP-dependent pathway. In contrast TPA when combined with maximally effective concentrations of either GHRH, forskolin or IBMX caused additional release of growth hormone, suggesting that the TPA-induced secretion involved a cyclic AMP-independent process. However, TPA also markedly potentiated the cellular cyclic AMP accumulation due to each of these agents. That TPA induced stimulation of basal and GHRH-stimulated cyclic AMP levels measured in the presence of IBMX suggests an action affecting cyclic AMP synthesis. Carbachol had no effect on basal or GHRH-stimulated growth hormone secretion or cyclic AMP levels. The two actions of TPA, one on secretion and one on cyclic AMP metabolism, may result from activation of some common event possibly involving protein kinase C. Our results suggest that GHRH and TPA activate independent pathways regulating growth hormone secretion.
Mol Cell Endocrinol 1988 Aug
PMID:Regulation of growth hormone secretion and cyclic AMP metabolism in ovine pituitary cells: interactions involved in activation induced by growth hormone-releasing hormone and phorbol esters. 246 92

The secretagogue effects of prolactin (PRL) and of various agents acting on cAMP levels, forskolin, cholera toxin and iloprost (a stable analogue of prostaglandin I2) have been assessed in lactating doe mammary gland fragments in vitro. Forskolin (10 microM), cholera toxin (1 microgram/ml) and iloprost (10 mM) stimulated milk casein secretion. The effects of forskolin (10 microM) and cholera toxin (1 microgram/ml) were potentiated by PRL (10 micrograms/ml). Conversely, the action of iloprost (10 microM) was not amplified by PRL (10 micrograms/ml). Forskolin (10 microM) and cholera toxin (1 microgram/ml) stimulated the intracellular accumulation of cAMP. Neither PRL nor iloprost, at concentrations which stimulated casein secretion, modified the accumulation of cAMP. These results demonstrate that PRL does not act directly by any increase in intracellular cAMP levels. However, stimulating effects of forskolin and cholera toxin on casein secretion and intracellular cAMP levels suggest that various transduction signals are effective in the mammary cells.
Mol Cell Endocrinol 1989 Aug
PMID:The actions of forskolin, cholera toxin and iloprost on casein secretion by lactating doe mammary glands. 247 50

The regulation of the insulin receptor by cAMP has been examined in glial C6 cells. Incubation for 48 h with dibutyryl cyclic AMP produced a dose-dependent inhibition of 125I-insulin binding to the cells. Other agents that elevate intracellular cAMP levels such as forskolin and cholera toxin mimicked the effect of this cyclic AMP analog. With all compounds the maximal decrease of binding was found between 24 and 48 h and normally varied between 40 and 60%. Forskolin, cholera toxin and dibutyryl cyclic AMP also affected C6 cell proliferation, and the dose-response for decreasing the receptor was very similar to that observed for the inhibition of cell growth, suggesting a relationship between both phenomena. Scatchard analysis showed that cAMP did not produce major changes in the affinity of the receptor for insulin, but rather decreased receptor number. An accumulation of receptors at the cell surface was observed in the absence of de novo protein synthesis, since cycloheximide caused a significant increase in insulin binding to the cells. This inhibitor almost totally blocked the cAMP effect both when added simultaneously to the cells with the agents which increase cAMP and when added to cells pre-treated for 48 h with the same compounds.
Mol Cell Endocrinol 1989 Feb
PMID:Effects of cyclic AMP elevation on the levels of insulin receptors in glial C6 cells. 253 40

The mechanism of cyclic AMP (cAMP) induction of fibronectin (FN) in HT-1080 and JEG-3 cells differs (D. C. Dean, R. F. Newby, and S. Bourgeois, J. Cell Biol. 106:2159-2170, 1988). In the fibrosarcoma cell line HT-1080, induction requires both protein synthesis and a lag period of 12 to 24 h. In the choriocarcinoma cell line JEG-3, protein synthesis is not required and induction peaks before 24 h, declining thereafter. We show that the FN promoter is transcribed in vitro and that the transcripts initiate at the proper site. Based on transfection experiments with these cells and FN promoter constructions, a cAMP-responsive element (CRE) was identified between -157 and -188 base pairs upstream of the human FN gene. This sequence also conferred cAMP inducibility in both cell lines on the herpesvirus thymidine kinase promoter when it was placed upstream of a thymidine kinase-chloramphenicol acetyltransferase fusion gene. DNase I protection analysis and gel retardation experiments revealed that the CRE was bound by a protein(s) that was present in both HT-1080 and JEG-3 cells as well as in NIH 3T3 cells. Multiple protein-CRE complexes were resolved by gel retardation with extracts of both cell lines. Forskolin treatment of these cells did not alter qualitatively or quantitatively the pattern of CRE-binding proteins that was observed. The FN promoter was at least 10 times more active in HT-1080 than in JEG-3 cells, even though in JEG-3 cells both the rate of FN biosynthesis and the level of accumulated FN mRNA were greater than those in HT-1080 cells. The difference in promoter activity in HT-1080 and JEG-3 cell was mediated by sequences that were located between positions -510 and -56. Deletion of the FN promoter from positions -510 to -56 resulted in an ~30-fold decrease in promoter activity when this construction was transfected into HT-1080 cells, and similar results were observed in NIH 3T3 cells; however, less than a 2-fold effect was observed in JEG-3 cells. Results of these studies suggest that there is some degree of tissue specificity of FN gene expression and reveal that cAMP induction is mediated, in part, by the same element (CRE) in both HT-1080 and JEG-3 cells.
Mol Cell Biol 1989 Apr
PMID:Forskolin inducibility and tissue-specific expression of the fibronectin promoter. 254 72

The role that the intracellular mediators, cAMP and Ca2+/phosphatidylserine-dependent protein kinase C, play in the regulation of endothelial cell (EC) motility was investigated. The adenylate cyclase activator, forskolin, at 10 microM induced rapid and reversible alterations in the shape of cultured human EC, disappearance of actin bundles and the concentration of F-actin at cell borders. Actin reorganization provoked by forskolin coincide with redistribution of vinculin to the cell periphery and rapid elimination of surface-associated fibronectin. A protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) at 10-100 microM induced no visible alterations of cell shape, but enhanced the effect of forskolin. PMA stimulated formation of "stress fibers" and increased the number of vinculin plaques in central areas of the cell. A decrease in the amount of the surface-associated fibronectin in PMA-treated cells has also been observed, but, this effect was considerably slower than that produced by forskolin. Forskolin, but not PMA stimulated phosphorylation of the major intermediate filament protein, vimentin.
J Mol Cell Cardiol 1989 Feb
PMID:Effects of forskolin and phorbol-myristate-acetate on cytoskeleton, extracellular matrix and protein phosphorylation in human endothelial cells. 254 28

The activity of the two cAMP-dependent protein kinases (PKa I and PKa II) was evaluated in dog thyroid cells in primary cultures after a 6-day growth period induced by either thyrotropin (TSH) or epidermal growth factor (EGF). Although the total PKa activity was not affected in cells cultured in the presence of TSH or EGF, their actions on the PKa I and PKa II expressions were significantly different. The activity of PKa I was strongly inhibited by TSH (70-80%) while with EGF it was either stimulated or unaffected with respect to controls. The two mitogens did not have a significant effect on the activity of PKa II. Forskolin (Fk) mimicked the effect of TSH. The expression of the two regulatory subunits (R I and R II), evaluated by the covalent binding of 8-azido-cAMP, was similar to the expression of the corresponding catalytic activities, suggesting a coregulation of the catalytic and regulatory subunits from the same isozyme. After chronic stimulation by TSH, differentiated dog thyroid cells are almost completely deprived of PKa I.
Mol Cell Endocrinol 1989 Jan
PMID:Thyrotropin but not epidermal growth factor down-regulates the isozyme I (PKa I) of cyclic AMP-dependent protein kinases in dog thyroid cells in primary cultures. 254 80

Transcription of the human proopiomelanocortin (POMC) gene is regulated by cAMP. To identify the region in the human POMC gene responsible for this regulation, we constructed chimeric genes containing different portions of the 5'-flanking region of the human POMC gene fused to the structural sequence encoding the bacterial reporter enzyme chloramphenicol acetyltransferase (CAT). The transcriptional activity of the fusion genes introduced into the rat glial cell line C6 was assayed by measuring CAT activity in the cell lysate. Forskolin, an adenylate cyclase-activating agent, stimulated the expression of POMC-CAT fusion genes. Deletion analysis demonstrated that the region between -417 and -97 bp from the transcriptional origin of the human POMC gene was responsible for regulation by cyclic AMP.
Mol Cell Endocrinol 1989 Mar
PMID:Cyclic AMP-responsive region of the human proopiomelanocortin (POMC) gene. 254 84

To determine the rat PRL (rPRL) promoter sequences that mediate pituitary-specific and cAMP-induced gene expression in vivo, various lengths of the rPRL promoter were ligated to the luciferase reporter gene and introduced into pituitary and non-pituitary cell lines. A 30-fold increase in rPRL promoter activity was observed in GH4 rat pituitary tumor cells compared to nonpituitary Rat2 fibroblast and HeLa cervical carcinoma cells. About 45% of this cell-specific promoter activity was competed by a plasmid containing the -67 to -45 rPRL promoter region, which is the most proximal binding site for a lactotroph-specific factor. Compared to a -425 rPRL construct, transfection with rPRL 5'-end points of -212, -178, and -127 contained 23%, 45%, and 1%, respectively, of luciferase activity. Forskolin stimulation resulted in a 10-fold induction of all the rPRL promoter fragments tested. Of note, a -127 deletion which was devoid of any basal promoter activity was also induced 10-fold by forskolin. The forskolin effect was abolished when GH4 rat pituitary cells were cotransfected with a plasmid encoding a protein kinase A inhibitor, indicating protein kinase A is involved in the activation mechanism. These data document that both positive and negative effectors influence basal rPRL promoter activity. Furthermore, the minimum sequences required for pituitary-specific rPRL promoter activity are altered by intracellular cAMP levels. Taken together, the data indicate that hormone-activated and cell-specific factors may interact to establish a particular setpoint for rPRL gene expression.
Mol Endocrinol 1989 May
PMID:Analysis of rat prolactin promoter sequences that mediate pituitary-specific and 3',5'-cyclic adenosine monophosphate-regulated gene expression in vivo. 254 56

Somatostatin (SRIF) is a 14-amino acid peptide hormone that is synthesized as part of a larger precursor, prepro-SRIF, consisting of a signal peptide and a proregion of 80-90 amino acids; mature SRIF is located at the carboxyl-terminus of the precursor. We have used a recombinant retroviral expression vector encoding anglerfish prepor-SRIF-I to infect rat pituitary GH3 cells. The aim of these studies was to investigate the intracellular storage and secretion of the total pool of endogenous GH compared to that of SRIF. Several clonal lines of GH3 cells expressing high or low levels of SRIF were treated with TRH, forskolin, or depolarizing concentrations of potassium, and the levels of intracellular and secreted GH or SRIF were determined using highly sensitive RIAs. Approximately 65% of the total GH was secreted basally, whereas less than 20% of the SRIF-immunoreactive material was basally secreted. Forskolin treatment or potassium depolarization stimulated GH release, but only about 50% above basal levels. In contrast, SRIF secretion was stimulated approximately 5-fold in response to these secretagogues. Based on its lower basal rate of secretion compared to GH and its enhanced release in response to a variety of secretagogues, we conclude that the heterologously expressed SRIF is preferentially targeted to the regulated pathway in GH3 cells.
Mol Endocrinol 1989 Oct
PMID:Retrovirus-mediated expression of preprosomatostatin in rat pituitary GH3 cells: targeting of somatostatin to the regulated secretory pathway. 257 12

The addition of TSH to FRTL-5 thyroid cells induces a 7- to 8-fold increase in the steady state level of malic enzyme [L-malate-NADP+ oxidoreductase (decarboxylating); EC 1.1.1.40] mRNA, but does not alter beta-actin mRNA levels. Insulin alone or together with TSH has no effect on malic enzyme mRNA. The effect of TSH is not the result of thyroid hormone formation, since the addition of T3 in the presence or in the absence of TSH and the addition of 5% serum (which includes T3 and T4) have no effect. Forskolin (10(-6) M) reproduces the TSH effect, suggesting that cAMP is involved.
Mol Endocrinol 1989 Mar
PMID:Thyrotropin increases malic enzyme messenger ribonucleic acid levels in rat FRTL-5 thyroid cells. 266 74


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