Stimulation of Adenosine 3′:5′-Cyclic Monophosphate Accumulation in Anterior Pituitary Gland
            <i>In Vitro</i>
            by Synthetic Luteinizing Hormone-Releasing Hormone

Borgeat, Pierre; Chavancy, Gerard; Dupont, André; Labrie, Fernand; Arimura, A.

doi:10.1073/pnas.69.9.2677

Cited by 183 publications

(47 citation statements)

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“…These data pertain to our studies on the plasma membrane receptor for thyrotropin-releasing hormone [1,2] and the observed stimulation of adenohypophyseal adenylate cyclase activity by synthetic thyrotropin (P. Borgeat, P. Garneau, and F. Labrie, unpublished data) and luteinizing hormone-releasing hormones [3] and by purified growth hormone-releasing hormone [4]. It is well known that cyclic AMP, or its derivatives, stimulate the release of adenohypophyseal hormones [5].…”

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confidence: 97%

Phosphorylation of Nuclear Proteins from Bovine Anterior Pituitary Gland Induced by Adenosine 3′:5′‐monophosphate

Jolicoeur

Labrie

1974

European Journal of Biochemistry

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In the presence of exogenous protein kinase dependent on adenosine 3' : 5'-monophosphate (cyclic AMP), cyclic AMP leads to an important stimulation of 32P incorporation into chromatin purified from bovine anterior pituitary tissue. Over 80% of 32P incorporated into isolated adenohypophyseal histones is associated with Fzb histone while small uptake is measured in F1 and F3 (and its dimer form) histones. Cyclic AMP leads to a 3 to 4-fold stimulation of incorporation of radioactivity into histone Fzb. The radioactivity associated with F2b histone is almost exclusively recovered into two phosphopeptides. Eigthteen bands can be resolved after separation of adenohypophyseal acidic nuclear proteins on 5 % sodium dodecylsulfate polyacrylamide gels and their apparent molecular weights range from 12000 to 300000. Protein kinase catalyses the cyclic-AMP-dependent phosphorylation of a large number of acidic proteins although preferential labeling occurs in five bands. The present data suggest a possible role of cyclic AMP on the transcriptional activity of the anterior pituitary gland through phosphorylation of histones and non-histone acidic nuclear proteins.We have recently obtained direct evidence for a role of the adenylate cyclase system as mediator of the action of at least three hypothalamic releasing hormones in the anterior pituitary gland. These data pertain to our studies on the plasma membrane receptor for thyrotropin-releasing hormone [1,2] and the observed stimulation of adenohypophyseal adenylate cyclase activity by synthetic thyrotropin (P. Borgeat, P. Garneau, and F. Labrie, unpublished data) and luteinizing hormone-releasing hormones [3] and by purified growth hormone-releasing hormone [4]. It is well known that cyclic AMP, or its derivatives, stimulate the release of adenohypophyseal hormones [5].Although the short-term stimulatory effect of cyclic AMP on total adenohypophyseal protein [6], growth hormone and prolactin [4] synthesis seems to be exerted at a translational level, it is likely that the long-term effects of the cyclic nucleotide, in the anterior pituitary gland, will include an action at a transcriptional level.Much evidence has accumulated to support the hypothesis that in many systems, cyclic-AMP-dependent protein kinase mediates the various intracellular effects of the cyclic nucleotide [7]. Many studies indicate that the phosphorylation of histones [8,9] and non-histone [lo--121 nuclear proteins can be correlated with the rate of RNA synthesis. Moreover, glucagon enhances the phosphorylation, at specific sites, of rat liver F1 histone [8] while insulin and prolactin increase the phosphorylation of nuclear proteins (both histones and non-histones) in mouse mammary epithelial cells in organ culture [13]. Chorionic gonadotropin has also been reported to enhance the phosphorylation of both histone and non-histone proteins in rat ovarian tissue [14].In bovine anterior pituitary gland, we have already found a high level of endogenous phosphorylation in the nuclear fraction [15]. It thus seeme...

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confidence: 97%

Phosphorylation of Nuclear Proteins from Bovine Anterior Pituitary Gland Induced by Adenosine 3′:5′‐monophosphate

Jolicoeur

Labrie

1974

European Journal of Biochemistry

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“…Activation of PKC then leads to activation of downstream protein kinases belonging to the MAPK family (9 -15). Activation of LHRH-R also triggers calcium influx, resulting in an increase in intracellular calcium (16) and cAMP levels (17,18) and leading to the activation of other protein kinases, such as the c-Jun N-terminal kinase (19,20). This LHRH-R-mediated pathway acts independently of the PKC and MAPK signaling pathways (21).…”

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confidence: 99%

The Luteinizing Hormone-releasing Hormone Inhibits the Anti-apoptotic Activity of Insulin-like Growth Factor-1 in Pituitary αT3 Cells by Protein Kinase Cα-mediated Negative Regulation of Akt

Rose

Froment

Perrot

et al. 2004

Journal of Biological Chemistry

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The luteinizing hormone-releasing hormone (LHRH) receptor is a G protein-coupled receptor involved in the synthesis and release of pituitary gonadotropins and in the proliferation and apoptosis of pituitary cells. Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor that has a mitogenic effect on pituitary cells. In this study, we used the ␣T3 gonadotrope cell line as a model to characterize the IGF-1R signaling pathways and to investigate whether this receptor interacts with the LHRH cascade. We found that IGF-1 activated the IGF-1R, insulin receptor substrate (IRS)-1, phosphatidylinositol 3-kinase, and Akt in a timedependent manner in ␣T3 cells. The MAPK (ERK1/2, p38, and JNK) pathways were only weakly activated by IGF-1. In contrast, LHRH strongly stimulated the MAPK pathways but had no effect on Akt activation. Cotreatment with IGF-1 and LHRH had various effects on these signaling pathways. 1) It strongly increased IGF-1-induced tyrosine phosphorylation of IRS-1 and IRS-1-associated phosphatidylinositol 3-kinase through activation of the epidermal growth factor receptor. 2) It had an additive effect on ERK1/2 activation without modifying the phosphorylation of p38 and JNK1/2. 3) It strongly reduced IGF-1 activation of Akt. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and cell cycle analysis revealed that, in addition to having an additive effect on ERK1/2 activation, cotreatment with IGF-1 and LHRH also had an additive effect on cell proliferation. The LHRH-induced inhibition of Akt stimulated by IGF-1 was completely blocked by Safingol, a protein kinase C (PKC) ␣-specific inhibitor, and by a dominant negative form of PKC␣. Finally, we showed that the inhibitory effect of LHRH on IGF-1-induced PKC␣-mediated Akt activation was associated with a marked reduction in Bad phosphorylation and a substantial decrease in the ability of IGF-1 to rescue ␣T3 cells from apoptosis induced by serum starvation. Our results demonstrate for the first time that several interactions take place between IGF-1 and LHRH receptors in gonadotrope cells. Luteinizing hormone-releasing hormone (LHRH)1 is a hypothalamic decapeptide, which plays a crucial role in normal reproductive function. In the pituitary, LHRH-I (mammalian LHRH) stimulates the synthesis and the release of the gonadotropins, LH and FSH, and promotes cell proliferation and apoptosis in pituitary cells (1, 2). The effects of LHRH-I are mediated by a cell surface receptor (LHRH-R) belonging to the G protein-coupled receptor superfamily (3, 4). LHRH-I binding to its cognate receptor leads to interaction of the receptor with heterotrimeric G proteins, including G q/11 . These G proteins in turn activate phospholipase C, leading to the production of diacylglycerol and the subsequent activation of protein kinase C (PKC) (5-9). Activation of PKC then leads to activation of downstream protein kinases belonging to the MAPK family (9 -15). Activation of LHRH-R also triggers calcium influx, resulting in an increase in intracellular c...

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“…It seems likely that these enzymes may regulate cyclic AMP concentrations in vivo. Since in the pituitary, Ca2 + is known to modulate the accumulation of cyclic AMP [20] and the present finding that Ca2+ modulates phosphodiesterase activity, it is likely that the concentration of Caz+ and the capacity of activator to bind Ca2+ may be one of the determining factors in regulating cyclic-AMP-mediated [19] and gonadotropin-induced lutropin release from anterior pituitary.…”

Section: Discussionmentioning

confidence: 99%

“…3': 5'-Cyclic-AMP phosphodiesterase (EC 3.1.4.17). in two or more molecular forms [l -151. Recent reports have described the existence of a protein modifier for cyclic nucleotide phosphodiesterases which require Ca2+ as cofactor [16-181. In rat anterior pituitary gland cyclic AMP presumably acts as a second messenger [19,20] in gonadoliberin-induced lutropin release. This effect is also mediated by Ca2+ [20,21].…”

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Cyclic Nucleotide Phosphodiesterases from Rat Anterior Pituitary. Characterization of Multiple Forms and Regulation by Protein Activator and Ca2+

Azhar

Menon

1977

Eur J Biochem

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Phosphodiesterase activities for adenosine and guanosine 3' : 5'-monophosphates (cyclic AMP and cyclic GMP) were demonstrated in particulate and soluble fractions of rat anterior pituitary gland. Both fractions contained higher activity for cyclic GMP hydrolysis than that for cyclic AMP hydrolysis when these activities were assayed at subsaturating substrate concentrations. Addition of protein activator and CaCl, to either whole homogenate, particulate or supernatant fraction stimulated both cyclic AMP and cyclic GMP phosphodiesterase activities. Almost 80% of cyclic AMP and 90% of cyclic GMP hydrolyzing activities were localized in soluble fraction. Particulate-bound cyclic nucleotide phosphodiesterase activity was completely solubilized with 1 % Triton X-100. Detergent-dispersed particulate and soluble enzymes were compared with respect to CaZ + and activator requirements and gel filtration profiles. Particulate, soluble and partially purified phosphodiesterase activities were also characterized in relation to divalent cation requirements, kinetic behavior and effects of Ca2+, activator and ethyleneglycol-bis-(2-aminoethyl)-N,N'-tetraacetic acid. Gel filtration of either sonicated whole homogenate or the 105000xg supernatant fraction showed a single peak of activity, which hydrolyzed both cyclic AMP and cyclic GMP and was dependent upon Ca2+ and activator for maximum activity. Partially purified enzyme was inhibited by 1-methyl-3-isobutylxanthine and papaverine with the concentration of inhibitor giving 50% inhibition at 0.4 pM substrate being 20 pM and 24 pM for cyclic AMP and 7 pM and 10 pM for cyclic GMP, respectively. Theophylline, caffeine and theobromine were less effective. The rat anterior pituitary also contained a protein activator which stimulated both pituitary cyclic nucleotide phosphodiesterase(s) as well as activator-deficient brain cyclic GMP and cyclic AMP phosphodiesterases. Chromatography of the sonicated pituitary extract on DEAE-cellulose column chromatography resolved the phosphodiesterase into two fractions. Both enzyme fractions hydrolyzed cyclic AMP and cyclic GMP and had comparable apparent K, values for the two nucleotides. Hydrolysis of cyclic GMP and cyclic AMP by fraction I1 enzyme was stimulated 6-7-fold by both pituitary and brain activator in the presence of micromolar concentrations of Ca2+.In most biological systems intracellular levels of cyclic AMP are regulated by the relative activities of hormone-responsive adenylate cyclase and cyclic AMP phosphodiesterase. Similarly, concentration of cyclic GMP is also maintained by relative activities of guanylate cyclase and cyclic GMP phosphodiesterase. Cyclic nucleotide phosphodiesterases are present in both cytoplasmic and particulate fractions of the cell [l -51 and in many tissues exists at least in two or more molecular forms [l -151. Recent reports have described the existence of a protein modifier for cyclic nucleotide phosphodiesterases which require Ca2+ as cofactor [16-181. In rat anterior pituitary gland cyclic AMP pres...

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Stimulation of Adenosine 3′:5′-Cyclic Monophosphate Accumulation in Anterior Pituitary Gland In Vitro by Synthetic Luteinizing Hormone-Releasing Hormone

Cited by 183 publications

References 50 publications

Phosphorylation of Nuclear Proteins from Bovine Anterior Pituitary Gland Induced by Adenosine 3′:5′‐monophosphate

Phosphorylation of Nuclear Proteins from Bovine Anterior Pituitary Gland Induced by Adenosine 3′:5′‐monophosphate

The Luteinizing Hormone-releasing Hormone Inhibits the Anti-apoptotic Activity of Insulin-like Growth Factor-1 in Pituitary αT3 Cells by Protein Kinase Cα-mediated Negative Regulation of Akt

Cyclic Nucleotide Phosphodiesterases from Rat Anterior Pituitary. Characterization of Multiple Forms and Regulation by Protein Activator and Ca2+

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