Phospholipid Turnover in Gonadotropin-Releasing Hormone Target Cells: Comparative Studies

Abstract

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; Hillensjo 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.