Phospholipid Turnover in Gonadotropin-Releasing Hormone Target Cells: Comparative Studies
Gonadotropin releasing hormone (GnRH) stimulates pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH) biosynthesis and release. Paradoxical antifertility effects of GnRH and its potent agonistic analogs in vivo have led to the findings that GnRH and its agonists also exert direct stimulatory and inhibitory gonadal effects (Hsueh and Jones, 1981; Hillensjö and Lemaire, 1980; Clark et al., 1980; Knecht and Catt, 1981; Ekholm et al., 1981; Hunter et al., 1982; Jones and Hsueh, 1982; Dekel et al., 1983; Hsueh et al., 1983; Knecht et al., 1983). The direct inhibitory effects are mainly observed after several hours of coculture of GnRH agonists and gonadotropins. The inhibitory effects might be explained by reversal of the inhibitory effect of FSH on ovarian phosphodiesterase activity and a progressive inhibition of adenylate cyclase (Knecht and Catt, 1981); and/or by inhibition of the side-chain cleavage enzyme and increase in 20-α hydroxysteroid dehydrogenase activity in the ovary (Jones and Hsueh, 1982). The testicular inhibitory effects might be explained by inhibition of 17α-hydroxylase and/or inhibition of 17–20 desmolase (Hsueh et al., 1983). The gonadal stimulatory effects of GnRH, which include stimulation of prostaglandin E (PGE) and steroid production, oocyte maturation and induction of ovulation are not clear at the present time. We have recently demonstrated that cyclic AMP (cAMP) is not involved in GnRH action in the pituitary and the gonads (Naor et al., 1978; and submitted). Therefore, we investigated the possible involvement of phosphatidylinositol (PI) turnover and PGE production in the mediation of GnRH action in both the pituitary and gonads.
KeywordsGranulosa Cell Phosphatidic Acid Oocyte Maturation Phosphatidic Acid GnRH Agonist
Unable to display preview. Download preview PDF.
- Fain, J.N., 1982, Involvement of phosphatidylinositol breakdown in elevation of cytosol Ca + by hormones and relationship to prostaglandin formation, in: “Hormone Receptors”, L.D. Kohn, ed., John Wiley and Sons, Ltd., p. 237.Google Scholar
- Kiesel, L., Naor, Z., and Catt, K.J., 1983, Mechanisms of GnRH action: Role of arachidonate metabolites and phosphatidic acid in the stimulation of cyclic GMP production and LH release in pituitary gonadotrophs, Proc. of the 65th Annual Meeting of the Endocrine Society, San Antonio, Abst. 561.Google Scholar
- Kirk, C.J., Creba, J.A., Downes, C.P., and Michell, R.H., 1981, Hormone-stimulated metabolism of inositol lipids and its relationship to hepatic receptor function, Biochem. Soc. Trans., 7: 377.Google Scholar
- Knecht, M., Ranta, T., Naor, Z., and Catt, K.J., 1983, Direct effect of GnRH on the ovary, in: “Factors Regulating Ovarian Function”, G.S. Greenwold and P.F. Terranova, eds., Raven Press, p. 225.Google Scholar
- Naor, Z., Zor, U., Meidan, R., and Koch, Y., 1978, Sex difference in pituitary cyclic AMP response to gonadotropin releasing hormone, Am. J. Physiol., 235: E37.Google Scholar
- Naor, Z., Vanderhoek, J.Y., Lindner, H.R., and Catt, K.J., 1983, Arachidonic acid products as possible mediators of the action of gonadotropin releasing hormone, in: “Advances in Prostaglandin Thromboxane and Leukotriene Research” B. Samuelsson, R. Paoletti and P. Ramwell, eds., Raven Press, Vol. 12, p. 259.Google Scholar
- Raymond, V., Veilleux, R., and Leung, P.C.K., 1982, Early stimulation of the phosphatidylinositol response by LHRH in an enriched population of gonadotrophs in primary culture, Proc. of the 64th Annual Meeting of the Endocrine Society, San Franciso, 821 (Abst.).Google Scholar
- Snyder, G.D., and Bleasdale, J.E., 1982, Effect of LHRH on incorpo- ration of [J P]-orthophosphate into phosphatidylinositol by dispersed anterior pituitary cells, Mol. Cell. Endocrinol. 28: 55.Google Scholar
- Zor, U., and Lamprecht, S.A., 1977, Mechanism of prostaglandin action in endocrine glands. in: “Biochemical Actions of Hormones”, G. Litwack, ed., Academic Press, Vol. 4, pp. 85.Google Scholar