| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
In an attempt to delineate the mechanism of inhibitory action of dopamine on hormone secretion from human pituitary cells, the effect of dopamine on hormone secretion was studied using adenomatous and nonadenomatous human pituitary cells in culture. High K^+u (50 mM) and the divalent cation ionophore A23187 (10 <micrn>g/ml) both elevated growth hormone (GH), prolatctin (PRL) and ACTH secretion, which was blocked by dopamine (10^<-7>M). When the cells were incubated in low calcium medium, secretion of these hormones was significantly inhibited. The addition of dopamine to low calcium medium further decreased hormone release. When the human somatotroph and lactotroph adenoma cells were loaded with a calcium sensitive probe fura-2/AM, dopamine caused a rapid decrease in both basal and stimulated cytosolic free calcium concentrations. Furthermore, activation of protein kinase C by 12-0-tetradecanoyl-13-acetate (TPA; 10^<-7>M) or 1-oleoyl-2-acetyl-glycerol (OAG; 20 <micrn>g/ml) resulted in
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elevation of GH secretion, which was inhibited by coincubation with dopamine. Forskolin (10^<-5>M) and phodiesterase inhibitors, theophylline (10^<-2>M) or IBMX (10^<-3>M), increased hormone secretion, which was again blocked by dopamine. No qualitative difference in these hormone responses was found in adenomatous and nonadenomatous human pituitary cells. Both in human somatotroph and lactotroph adenoma cells obtained from patients, cAMP generation was correlated with hormone release. Exposure of the cells to dopamine resulted in a parallel decrease in intracellular cAMP content and hormone secretion. These results suggests that an increase in cytosolic free calcium caused by either mobilization from intracellular calcium pools or influx from the extracellular compartment, acivation of protein kinase C and intracellular cAMP accululation may be involved in the mechanism of hormone secretion from human pituitary cells, and that dopamine may influence these messengers to suppress pituitary hormone secretion. Less
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