The ancient Chinese formula Longdan Xiegan Tang improves antipsychotic-induced hyperprolactinemia by repairing the hypothalamic and pituitary TGF-β1 signaling in rats

Abstract

Ethnopharmacological relevanceAntipsychotics often induce hyperprolactinemia. The transforming growth factor (TGF)-beta1 signaling in the pituitary and hypothalamus inhibits prolactin synthesis and secretion, and its impairment is implicated in neuropsychiatric disorders. Longdan Xiegan Tang (LXT) alone or together with antipsychotics have been used to treat various neuropsychiatric diseases and hyperprolactinemia-associated disorders. Aim of the studyTo investigate the effect of LXT on hyperprolactinemia and involvement of the TGF-beta1 signaling. Materials and methodsMale rats were co-administered with olanzapine (5 mg/kg) and LXT extract (50 and 500 mg/kg) (p.o., × 8 weeks). Plasma concentrations of prolactin and TGF-beta1 were determined by ELISA. Protein expression was analyzed by Western blot. ResultsTreatment of rats with LXT extract suppressed olanzapine-induced increase in plasma prolactin concentration and overexpression of pituitary and hypothalamic prolactin protein. Importantly, LXT restored olanzapine-induced decrease in protein expression of the key components of the TGF-beta1 signaling, TGF-beta1, type II TGF-beta receptor, type I TGF-beta receptor and phosphorylated SMAD3 in the pituitary and hypothalamus. Further, it antagonized downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein level, and inhibited pituitary estrogen receptor (ER) alpha and ERbeta protein expression. ConclusionsThe present results suggest that LXT ameliorates antipsychotic-induced hyperprolactinemia in rats by repairing the pituitary and hypothalamic TGF-beta1 signaling possibly via D2R, ERs or/and other pathways. Our findings may also provide scientific elucidation for use of the ancient Chinese formula to treat the impaired TGF-beta1 signaling-associated neuropsychiatric disorders.