Our observations demonstrate for the first time that the ether linked phospholipid AGEPC (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine, PAF) stimulates PRL and GH release. Our goal is to determine the involvement of AGEPC in the physiological regulation of anterior pituitary function. The action of AGEPC on the secretion of all hormones from the pituitary will be examined and characterized in respect to dose effects, reversibility, and specificity. Also the factors which modulate response to AGEPC will be characterized including estrogen, glucocorticoids, thyroid hormone and age of donor rat. The mechanism of action of AGEPC will be examined by measuring its effects on polyphosphotidylinositol metabolism, calcium mobilization and arachidonic acid release. The interactions between AGEPC and other known physiological secretogogues will be determined in order to establish additivity or synergyism. Possible sources for AGEPC will examined. This will be determined by measuring the ability of anterior pituitary/hypothalamic tissue to synthesize AGEPC in response to a stimulus. In order to provide substantiating evidence AGEPC precursor will be measured in pituitary membrane, the presence of acetyltransferase (essential and receptor modulated enzyme in the biosynthesis of AGEPC) activity will be quantified and the kinetics of AGEPC metabolism will be determined. If pituitary hypothalamic tissue can form AGEPC, the ability of releasing factors to stimulate AGEPC formation will be determined. In order to examine extrapituitary/extrahypothalamic sources as well as to assess the physiological implications of AGEPC action on anterior pituitary tissue, specific AGEPC receptor antagonists will be given to intact rats and the effects on pituitary hormone secretion will be monitored. All procedures except for antagonist studies will be done on cultures of rat anterior or hypothalamic tissue. Where biochemical responses are monitored individual pituitary cell types will be isolated in order to establish the cell type responding and to evaluate paracrine interactions. Procedures for isolation of AGEPC will employ HPLC. Identification of formed AGEPC will include both biological activity and chemical analysis using mass spectrometry. The long term significance of this project includes illucidation of the signal transduction mechanisms occurring within the pituitary. Specifically the role of AGEPC as a modulator of the action of arachidonate metabolites and the paracrine action of AGEPC will be assessed.
| Grandison, L (1990) Platelet activating factor induces inositol phosphate accumulation in cultures of rat and bovine anterior pituitary cells. Endocrinology 127:1786-91 |
| Camoratto, A M; Grandison, L (1989) Platelet-activating factor stimulates prolactin release from dispersed rat anterior pituitary cells in vitro. Endocrinology 124:1502-6 |
