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Ann Clin Biochem 1992; 29: 477-480
Is extrapituitary action of gonadotrophin-releasing hormone biologically significant? Atsushi Imai, Tatsuro Furui and Teruhiko Tamaya From the Department of Obstetrics and Gynecology, Gifu University School of Medicine, Tsukasamachi, Gifu 500, Japan
Additional key phrases: ovarian function; hormone-secretory tumours Gonadotrophin-releasing hormone (Gn-RH) mediates the hypothalamic control of pituitary gonadotrophin (Gn) secretion. During the last decade, evidence has accumulated to suggest that Gn-RH and its agonists can exert extrapituitary effects via specific tissue receptors which have been identified in many tissues such as the ovary and certain hormone-sensitive tumours.t-' the stimulation of Gn-RH receptor suppresses Gndependent maturation and steroidogenesis in the ovary, and expresses the antigrowth signal in the tumours. In contrast to a correlation between the direct extrapituitary effects of Gn-RH and the presence of Gn-RH binding sites in the cells, the physiological role of the extrapituitary Gn-RH receptor is not clear. DOES THE EXTRAPITUITARY ACTION OF Gn-RH SERVE A PHYSIOLOGICALLY IMPORTANT ROLE IN OVARIAN FUNCTION? Circumstantial observations first suggested the possibility that Gn-RH may act at the level of the gonads. Although Gn-RH stimulates pituitary Gn production, pharmacological doses in continuous or repeated administration of Gn-RH or its agonists have been shown to cause paradoxical anti-fertility effects in several species, including primates.>!' Gn-RH-induced interruptions of reproductive cycles and pregnancy are associated with diminished ovarian steroidogenesis, implying impaired function of the corpus luteumr" These luteolytic effects have been attributed to the well recognized desensitizing actions of elevated luteinizing hormone (LH) levels on ovarian LH receptors and steroidogenesis,7,8,12,13 subsequent Correspondence: Dr A lmai.
to Gn-RH induced gonadotrophin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum sex steroid levels during early pregnancy, whereas a highly active Gn-RH analogue is effective in this regard.v !' In addition, Gn-RH and its agonists inhibit human chorionic Gn (hCG)-induced ovarian and uterine weight gain in hypophysectomized rats" and delay the onset of puberty in intact female rats. 4,15 In 1979, Gn-RH and its agonists were found to inhibit steroidogenesis induced by folliclestimulating hormone (FSH) in cultured granulosa cells." The subsequent literature by Clayton et al.,17 which examined the effects of Gn-RH agonists on luteal steroidogenesis, demonstrated the existence of such actions and their mediation by specific high-affinity receptor sites of Gn-RH present in luteal cell membranes. The interaction of Gn-RH and receptor induces membrane phosphoinositide breakdown18-21 and thereby activation of protein kinase C22-24 in the luteal cells and the granulosa cells. The effects of GnRH on Gn-dependent responses cannot be ascribed to interference with Gn binding, thus implying that Gn-RH and its agonists act at a stage after Gn-receptor interaction.Pw' Taken together with the finding that protein kinase C activator can mimic such actions of Gn_RH,22-25 the protein kinase C activation linked to phosphoinositide breakdown appears to function as an intracellular messenger for Gn-RH action on the Gn-responses.P'
Ann Clin Biochem 1992; 29: 477-480
Is extrapituitary action of gonadotrophin-releasing hormone biologically significant? Atsushi Imai, Tatsuro Furui and Teruhiko Tamaya From the Department of Obstetrics and Gynecology, Gifu University School of Medicine, Tsukasamachi, Gifu 500, Japan
Additional key phrases: ovarian function; hormone-secretory tumours Gonadotrophin-releasing hormone (Gn-RH) mediates the hypothalamic control of pituitary gonadotrophin (Gn) secretion. During the last decade, evidence has accumulated to suggest that Gn-RH and its agonists can exert extrapituitary effects via specific tissue receptors which have been identified in many tissues such as the ovary and certain hormone-sensitive tumours.t-' the stimulation of Gn-RH receptor suppresses Gndependent maturation and steroidogenesis in the ovary, and expresses the antigrowth signal in the tumours. In contrast to a correlation between the direct extrapituitary effects of Gn-RH and the presence of Gn-RH binding sites in the cells, the physiological role of the extrapituitary Gn-RH receptor is not clear. DOES THE EXTRAPITUITARY ACTION OF Gn-RH SERVE A PHYSIOLOGICALLY IMPORTANT ROLE IN OVARIAN FUNCTION? Circumstantial observations first suggested the possibility that Gn-RH may act at the level of the gonads. Although Gn-RH stimulates pituitary Gn production, pharmacological doses in continuous or repeated administration of Gn-RH or its agonists have been shown to cause paradoxical anti-fertility effects in several species, including primates.>!' Gn-RH-induced interruptions of reproductive cycles and pregnancy are associated with diminished ovarian steroidogenesis, implying impaired function of the corpus luteumr" These luteolytic effects have been attributed to the well recognized desensitizing actions of elevated luteinizing hormone (LH) levels on ovarian LH receptors and steroidogenesis,7,8,12,13 subsequent Correspondence: Dr A lmai.
to Gn-RH induced gonadotrophin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum sex steroid levels during early pregnancy, whereas a highly active Gn-RH analogue is effective in this regard.v !' In addition, Gn-RH and its agonists inhibit human chorionic Gn (hCG)-induced ovarian and uterine weight gain in hypophysectomized rats" and delay the onset of puberty in intact female rats. 4,15 In 1979, Gn-RH and its agonists were found to inhibit steroidogenesis induced by folliclestimulating hormone (FSH) in cultured granulosa cells." The subsequent literature by Clayton et al.,17 which examined the effects of Gn-RH agonists on luteal steroidogenesis, demonstrated the existence of such actions and their mediation by specific high-affinity receptor sites of Gn-RH present in luteal cell membranes. The interaction of Gn-RH and receptor induces membrane phosphoinositide breakdown18-21 and thereby activation of protein kinase C22-24 in the luteal cells and the granulosa cells. The effects of GnRH on Gn-dependent responses cannot be ascribed to interference with Gn binding, thus implying that Gn-RH and its agonists act at a stage after Gn-receptor interaction.Pw' Taken together with the finding that protein kinase C activator can mimic such actions of Gn_RH,22-25 the protein kinase C activation linked to phosphoinositide breakdown appears to function as an intracellular messenger for Gn-RH action on the Gn-responses.P'
