BES2005 Oral Communications Oral Communication 2: Reproduction and growth (8 abstracts)
A novel autocrine/paracrine inside-out signalling pathway that cross-talk the prostanoid and GnRH receptors in pituitary cells
Z Naor 1,2 , M Naidich 2 , AJ Pawson 1 , K Morgan 1 , S Battersby 1 , S MacPherson 1 , M Millar 1 , HN Jabbour 1 & RP Millar 1
1MRC Human Reproduction Sciences Unit, University of Edinburgh, Chancellor's Building, Edinburgh, UK; 2Department of Biochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
Pituitary gonadotropes (LH and FSH producing cells) are simultaneously exposed to numerous stimuli, which exert multiple signalling pathways that cross-talk with the GnRH receptor (GnRHR). A model downstream effector system is the prostanoid family. Hence, prostanoid receptors and GnRHR might cross-talk and affect the biological responses of the gonadotropes. Here we report the expression of prostaglandin (PG) PGE2 receptors EP1, EP2, EP3 and EP4, the PGF2alpha receptor FP and the PGI2 receptor IP in the rat pituitary. Interestingly, EP1, EP2, IP and FP seem to co-localize only to gonadotropes and EP3 only to mammotropes. Surprisingly, EP1, EP2, EP3, EP4, FP and IP were all detected in the gonadotrope cell line LbetaT2. GnRH stimulates phospholipase A2 (PLA2) activity. Surprisingly, we found the expression of sPLA2IIE, sPLA2V, iPLA2-A, iPLA2-gamma, cPLA2beta and cPLA2gamma, but not the ubiquitously expressed cPLA2alpha in LbetaT2 cells. Both COX-1 and COX-2 are expressed in LbetaT2 cells and the PKC and MEK inhibitors GF109203X and PD98059 markedly reduced the marked induction of COX-2 by GnRH respectively, indicating the involvement of PKC to ERK signalling in GnRH-induced COX-2 expression. COX1/2 expression by GnRH is followed by production of PGE2 and PGF2alpha and their exogenous addition affect the down-stream signalling and biological responses of activated GnRHR in LbetaT2 cells. Thus, sub-specialization exists among various pituitary cells in expressing different prostanoid receptors. GnRH-stimulated prostanoids exert a novel autocrine/paracrine inside-out signalling that affect the biological responses of pituitary cells. The results open a new vista into understanding the global and integrative signalling network of the pituitary gonadotope, which might be relevant to pituitary development, reproduction and pituitary tumours.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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