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18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models

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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.

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Abbreviations

GA:

18β-Glycyrrhetinic acid

PRL:

Prolactin

hyperPRL:

Hyperprolactinemia

BMT:

Bromocriptine

5-HT:

Serotonin

PRFs:

Prolactin-releasing factors

VIP:

Oxytocin and vasoactive intestinal peptide

GABA:

Forebrain γ-aminobutyric acid

TIDA:

Tuberoinfundibular dopaminergic

MCP:

Metoclopramide

E2:

Estradiol

T:

Testosterone

P:

Progesterone

FSH:

Follicle-stimulating hormone

LH:

Luteinizing hormone

GH:

Growth hormone

ELISA:

Enzyme-linked immunosorbent assays

PMSF:

Phenylmethanesulfonyl fluoride

DA:

Dopamine

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

HRP:

Horseradish peroxidase

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Acknowledgments

This work was supported by the Natural Science foundation of P. R. China (Grant No. 81402955) and General Research Fund (GRF) of Research Grant Council of HKSAR (Grant No. 785813).

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Authors and Affiliations

  1. School of Life Sciences, Jilin University, Changchun, 130012, China

    Di Wang, Yongfeng Zhang, Chunyue Wang, Dongxu Jia, Guangsheng Cai, Jiahui Lu & Di Wang

  2. School of Chinese Medicine, The University of Hong Kong, Hong Kong, China

    Zhang-Jin Zhang

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Wang, D., Zhang, Y., Wang, C. et al. 18β-Glycyrrhetinic Acid, a Novel Naturally Derived Agent, Suppresses Prolactin Hyperactivity and Reduces Antipsychotic-Induced Hyperprolactinemia in In Vitro and In Vivo Models. Neurochem Res 41, 2233–2242 (2016). https://doi.org/10.1007/s11064-016-1938-5

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