Phorbol ester inhibits luteinizing hormone-, forskolin-, and dibutyryl cyclic AMP-induced progesterone production in chicken granulosa cells

1989 ◽  
Vol 67 (2) ◽  
pp. 122-125 ◽  
Author(s):  
Elikplimi K. Asem ◽  
Benjamin K. Tsang
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Luteinizing Hormone ◽  
Cyclic Amp ◽  
Phorbol Ester ◽  
Granulosa Cells ◽  
Appreciable Effect ◽  
Dibutyryl Cyclic Amp ◽  
Progesterone Production ◽  
Kinase C

The possible role of protein kinase C in avian granulosa cell steroidogenesis was studied in vitro by examining the effect of tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) on progesterone synthesis in chicken granulosa cells in short-term (3 h) incubations. TPA (1–100 nM) caused a marginal but nonsignificant increase in progesterone production in granulosa cells isolated from the largest preovulatory follicle. When incubated in combination with luteinizing hormone (5–100 ng/mL), TPA suppressed the stimulatory effects of submaximally and maximally effective doses of the gonadotropin in a concentration-related manner. Similarly, the phorbol ester inhibited the steroidogenic responses to forskolin and dibutyryl cyclic AMP. By comparison, TPA had no appreciable effect on the metabolism of exogenous pregnenolone substrate to progesterone. Our data indicate that the tumor-promoting phorbol ester influences steroidogenic steps distal to cyclic AMP generation but at or before pregnenolone formation, and that protein kinase C may be a negative regulator of steroid biosynthesis in chicken granulosa cells.Key words: phorbol ester, granulosa cells, steroidogenesis, chicken.

scholarly journals Protein kinase C activity mediates LH-induced ErbB/Erk signaling in differentiated hen granulosa cells

Reproduction ◽  
2007 ◽  
Vol 133 (4) ◽  
pp. 733-741 ◽  
Author(s):  
Dori C Woods ◽  
A L Johnson
Keyword(s):  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Granulosa Cells ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Progesterone Production ◽  
Kinase C ◽  
Egf Family

While there is accumulating evidence that mitogen-activated protein kinase/Erk and protein kinase C (PKC) signaling inhibits premature differentiation of granulosa cells in hen prehierarchal follicles, it has only recently been established that these signaling pathways play an important facilitory role in promoting steroidogenesis in differentiated granulosa cells from preovulatory follicles. The present studies were conducted with differentiated granulosa cells to establish the ability of LH to initiate PKC activity, and the subsequent requirement for PKC activity in promoting the ErbB/Erk signaling cascade that ultimately facilitates LH-induced progesterone production. Incubation of differentiated granulosa cells with LH increases PKC activity within 15 min, and latently promotes Erk phosphorylation (P-Erk) by 180 min. Inhibition of PKC activity with GF109203X attenuates LH- and 8-bromo-cAMP (8-br-cAMP)-induced P-Erk, but not P-Erk promoted by an epidermal growth factor (EGF) family ligand (e.g., transforming growth factor α). Importantly, inhibition of PKC activity also blocks the LH-induced increase in the autocrine expression of mRNA encoding the EGF family ligands, such as EGF, amphiregulin, and betacellulin. Furthermore, inhibition of EGF ligand shedding at the level of the cell membrane using the matrix metalloprotease activity inhibitor, GM6001, prevents both LH- and 8-br-cAMP-induced P-Erk and progesterone production. These findings provide evidence for a facilitory role of PKC and ErbB/Erk signaling in LH-induced progesterone production, place the requirement for PKC activation upstream of ErbB/Erk activity, and demonstrate for the first time in a non-mammalian vertebrate the requirement for PKC activity in LH-induced expression of EGF family ligands in granulosa cells.

scholarly journals 1,2-Diacylglycerols overcome cyclic AMP-mediated inhibition of phosphatidylcholine synthesis in GH3 pituitary cells

1990 ◽  
Vol 267 (1) ◽  
pp. 17-22 ◽  
Author(s):  
R N Kolesnick
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Phorbol Esters ◽  
Pituitary Cells ◽  
Dibutyryl Cyclic Amp ◽  
Kinase C ◽  
Low Concentrations ◽  
High Concentrations ◽  
Phosphatidylcholine Synthesis

Previous studies showed that phorbol esters and thyrotropin-releasing hormone (TRH) stimulated phosphatidylcholine synthesis via protein kinase C in GH3 pituitary cells [Kolesnick (1987) J. Biol. Chem. 262, 14525-14530]. In contrast, 1,2-diacylglycerol-stimulated phosphatidylcholine synthesis appeared independent of protein kinase C. The present studies compare phosphatidylcholine synthesis stimulated by these agents with inhibition via the cyclic AMP system. The potent phorbol ester phorbol 12-myristate 13-acetate (PMA, 10 nM) increased [32P]Pi incorporation into phosphatidylcholine at 30 min to 159 +/- 6% of control. The adenylate cyclase activator cholera toxin (CT; 10 nM) and the cyclic AMP analogue dibutyryl cyclic AMP (1 mM) abolished this effect. CT similarly abolished TRH-induced phosphatidylcholine, but not phosphatidylinositol, synthesis. This is the first report of inhibiton of receptor-mediated phosphatidylcholine synthesis by the cyclic AMP system. The 1,2-diacylglycerol 1,2-dioctanoylglycerol (diC8) also stimulated concentration-dependent phosphatidylcholine synthesis. DiC8 (3 micrograms/ml) induced an effect quantitatively similar to that of maximal concentrations of PMA and TRH, whereas a maximal diC8 concentration (30 micrograms/ml) stimulated an effect 3-4-fold greater than these other agents. CT decreased the effect of diC8 (3 micrograms/ml) by 80%. Higher diC8 concentrations overcame the CT inhibition. Similar results were obtained with dibutyryl cyclic AMP. Additional differences were found between low and high concentrations of diC8. Low concentrations of diC8 failed to induce additive phosphatidylcholine synthesis with maximal concentrations of PMA, whereas high concentrations were additive. Hence, low concentrations of 1,2-diacylglycerols appear to be regulated similarly to phorbol esters, and higher concentrations appear to act via a pathway unavailable to phorbol esters.

scholarly journals Regulation of pp90rsk phosphorylation and S6 phosphotransferase activity in Swiss 3T3 cells by growth factor-, phorbol ester-, and cyclic AMP-mediated signal transduction.

1991 ◽  
Vol 11 (4) ◽  
pp. 1861-1867 ◽  
Author(s):  
R H Chen ◽  
J Chung ◽  
J Blenis
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Phorbol Ester ◽  
Kinase Activity ◽  
Sodium Vanadate ◽  
S6 Kinase ◽  
Kinase C

Somatic cell homologs to the Xenopus laevis S6 protein kinases (referred to collectively as pp90rsk) have recently been identified and partially characterized. Here we examine alterations in pp90rsk phosphorylation and S6 phosphotransferase activity in response to regulators of multiple signal transduction systems: purified growth factors, phorbol ester, changes in cyclic AMP (cAMP) levels, and sodium vanadate. All reagents tested increased pp90rsk serine and threonine phosphorylation, but only those agents that regulate cell proliferation and sodium vanadate activated its S6 kinase activity. In addition to the cAMP-stimulated phosphorylation of pp90rsk, a simple correlation between the extent of growth-regulated pp90rsk phosphorylation and S6 phosphotransferase activity was not observed. Quantitative phosphorylation of pp90rsk continued to increase after its S6 kinase activity began its return towards basal levels. However, a close correlation between the appearance and disappearance of a slow-mobility form of phosphorylated pp90rsk (by electrophoresis) and pp90rsk activity was observed. In addition, pp90rsk was regulated by both protein kinase C-independent and -dependent signaling mechanisms. The extent of protein kinase C participation, however, varied depending on which growth factor receptor was activated. Furthermore, growth factor-specific differences in the temporal regulation of pp90rsk S6 phosphotransferase activity were also observed. These results support the notion that the complex regulation of the rsk gene product constitutes one of the primary responses of animal cells to mitogenic signals.

Different Modulation of Protein Kinase C Isozymes in Dibutyryl Cyclic AMP-Differentiated PC12h Cells

2002 ◽  
Vol 63 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Yukiko Uehara-Kunugi ◽  
Shun Shimohama ◽  
Hitoshi Kobayakawa ◽  
Hitomi Tamura ◽  
Takashi Taniguchi
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Dibutyryl Cyclic Amp ◽  
Kinase C ◽  
Pc12h Cells
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