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Hong Zhou, Yonghua Jiang, Wendy K W Ko, Wensheng Li and Anderson O L Wong

. Furthermore, we also speculate that (i) the JAK2/MAPK cascades secondary coupled to the cAMP-dependent pathway and (ii) the PI3K cascade independent of cAMP-mediated mechanisms may be the key elements in the signal transduction for LH-induced GH gene

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D Roberts and D J Smith

INTRODUCTION

The hormone erythropoietin (EPO), released under hypoxic conditions, acts primarily to stimulate erythrocyte (RBC) production. The association between lack of oxygen, a blood-borne compound, and RBC formation was suggested as early as at the turn of the century (Carnot & DeFlandre, 1906), but it was not until 1957 that the kidneys were identified as the major site of EPO production in the adult mammal (Jacobson et al. 1957). The first purification of EPO was from plasma of anaemic sheep in 1971 (Goldwasser & Kung, 1971). Despite an extensive procedure, the yield and specific activity of the product were extremely low (0·4% and 8250 U/mg protein respectively). In 1977, the same procedure was used with 2550 litres of urine from anaemic humans, generating a product with a specific activity of 74 000 U/mg protein (Miyake et al. 1977). Characterization of the hormone was hampered by the difficulty of obtaining a

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V. C. Parrow, J. O. Gordeladze, E. J. Paulssen, P. Aleström and K. M. Gautvik

ABSTRACT

In GH12C1 rat pituitary cells treated with 5-azacytidine, the stimulatory effects exerted by vasoactive intestinal peptide (VIP), the GTP analogue guanyl-5′-yl imidodiphosphate (Gpp(NH)p), 12-O-tetradecanoyl phorbol 13-acetate, cholera toxin and pertussis toxin on the membrane-bound adenylyl cyclase were almost completely abolished. The corresponding inhibitory effect of somatostatin was increased. Alterations in adenylyl cyclase responsiveness began at the end of the drug treatment, and were most pronounced on day 5 after removal of 5-azacytidine. The cells subsequently and completely recovered after 10 days in the absence of the drug. Measurements of cholera toxin- and VIP-enhanced cyclic AMP levels in intact cells confirmed these results, and VIP appeared to have no stimulatory effect on GH secretion after 5-azacytidine treatment. Down-regulation of Gαs RNA also occurred on day 5 after cessation of drug treatment. ADP-ribosylation subsequent to stimulation with pertussis toxin was markedly increased, indicating an enhancement of Gαi and/or GGαo. Furthermore, both basal and Gpp(NH)p-stimulated phospholipase C activities were augmented by pre-exposure to 5-azacytidine.

Treatment of GH12C1 rat pituitary tumour cells with 5-azacytidine therefore causes a marked but temporary increase in the ratio of Gαi/Gαs protein levels.

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B Gallwitz, M Witt, U R Fölsch, W Creutzfeldt and W E Schmidt

ABSTRACT

Glucagon-like peptide-1(7–36)amide (GLP-1(7–36) amide) and gastric inhibitory polypeptide (GIP), peptides of the glucagon family, stimulate insulin secretion in vitro and in vivo. They possess high N-terminal sequence homology. Binding studies with 125I-labelled GIP and 125I-labelled GLP-1(7– 36)amide were performed in RINm5F insulinoma cells to investigate receptor specificity and to compare both receptors directly. Both binding sites were highly ligand-specific: GIP did not bind to the GLP-1(7–36)amide receptor and vice versa. Both peptides increased intracellular cyclic AMP levels; GLP-1(7– 36)amide was 100-fold more potent in stimulating cyclic AMP production when compared with GIP. At ranges of 1–10 nmol GLP-1(7–36)amide/1 and 0·1–10 GIP/1, corresponding to submaximal binding concentrations, the hormones showed an additive effect on cyclic AMP production. The N-terminal portion of GIP was important for binding, as GIP(1–30) showed almost full binding and biological activity. GIP(17–42) bound in a concentration-dependent manner with approximately 500-fold lower potency than GIP. At concentrations of up to 10 μmol GIP(17–42)/1 no stimulation of cyclic AMP was observed.

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Fabiana Cornejo Maciel, Paula Maloberti, Isabel Neuman, Florencia Cano, Rocío Castilla, Fernanda Castillo, Cristina Paz and Ernesto J Podestá

–45 min) proved to modify the intracellular content of MTE-I (data not shown). However, ACTH produces an increase of ACS4 levels evaluated by Western blot. Analysis of the intensity of ACS4 signal demonstrated that ACTH (10 mIU/ml) induces ACS4 levels to

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C Bignon, N Daniel, L Belair and J Djiane

The recent finding that sheep had long (l-oPRLR) and short (s-oPRLR) prolactin receptors provided new tools to further explore prolactin signaling to target genes. Here we used CHO cells transfected with l-oPRLR or s-oPRLR cDNAs to compare the activation of known key steps of prolactin signaling by the two receptors. We found that prolactin stimulated l-oPRLR tyrosine phosphorylation, although it lacked the last tyrosine residue found in other long prolactin receptors. In addition, l-oPRLR and s-oPRLR both responded to prolactin stimulation by (1) Janus kinase 2 (Jak2) tyrosine phosphorylation, (2) DNA-binding activation of signal transducer and activator of transcription 5 (STAT5), (3) stimulation of transcription from a promoter made of six repeats of STAT5-responsive sequence. However, although it contains STAT5-binding consensus sequences, the ovine beta-lactoglobulin promoter (-4000 to +40) was transactivated by l-oPRLR, but not by s-oPRLR. Taken together, our results indicate that activation of Jak2/STAT5 pathway alone is not sufficient to account for prolactin-induced transcription of this milk protein gene, and that sequences of its promoter, other than STAT5-specific sequences, account for the opposite transcriptional activation capabilities of l-oPRLR and s-oPRLR.

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Samantha Gardner, Emmanouil Stavrou, Patricia E Rischitor, Elena Faccenda and Adam J Pawson

Introduction GnRH occupancy of GnRH receptors leads to the activation of multiple signal transduction pathways ( Naor 1997 , 2009 , Naor et al . 2000 , Millar et al . 2004 , 2008 , Caunt et al . 2006 , Dobkin-Bekman et al . 2006 ). In

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Zhao Yang, Zhi-Li Huang and Ya-Xiong Tao

confirmed its importance in receptor expression, ligand binding, signal transduction and internalization ( Ernst et al . 2000 , Marin et al . 2000 , Tetsuka et al . 2004 , Faussner et al . 2005 , Kuwasako et al . 2011 ). In the present study, we

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I K Lund, J A Hansen, H S Andersen, N P H Møller and N Billestrup

genes through DNA binding ( Ahima & Flier 2000 , Levy & Darnell 2002 ). The mechanisms controlling and terminating the leptin signal transduction seem more elusive but are believed to include (i) internalisation and degradation of the leptin

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J Kim, L Jia, M R Stallcup and G A Coetzee

alterations and androgen-independent activation of AR via various signal transduction pathways ( Feldman & Feldman 2001 ). These mechanisms are not mutually exclusive but may in fact constitute compensatory measures that cooperate to establish androgen