title: 18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models.
abstract: The purpose of this study was to examine the effects of 18β-glycyrrhetinic acid (GA), a novel naturally derived agent, in suppressing prolactin (PRL) hyperactivity and reducing antipsychotic-induced hyperprolactinemia (hyperPRL) and the underlying mechanisms in in vitro and in vivo models. GA treatment for 24 h inhibited PRL synthesis and secretion in MMQ cells and cultured pituitary cells in a dose-dependent fashion; but this effect was not reproduced in GH3 cells that lack the expression of functional dopamine D2 receptors. GA suppressed elevated PRL level and growth hormone, and normalized several sex hormones in a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide. GA also modulated the expression 5-HT1A and 5-HT2A receptors in both in vivo and in vitro models. These results indicate that GA is effective in suppressing PRL hyperactivity caused by the blockade of dopamine D2 receptors. This suppressive effect of GA may be related to its modulation of the serotonergic system. This study provides additional evidence in support of GA as an adjunct for the treatment of hyperPRL.
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Chunyue
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: Jia
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Guangsheng
authors.initials: G
authors.lastname: Cai
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Lu
authors.affiliation: School of Life Sciences, Jilin University, Changchun, 130012, China. jluwangdi@outlook.com.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, Hong Kong, China. zhangzj@hku.hk.
authors.forename: Zhang-Jin
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000188:drug therapy*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; C119129:18alpha-glycyrrhetinic acid; D011388:Prolactin; D006034:Glycyrrhetinic Acid; D004298:Dopamine
keywords: 18β-Glycyrrhetinic acid; Hormones; Hyperprolactinemia; Serotonergic system