Research paperStudies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model
Introduction
Hyperprolactinemia (hyperPRL), a clinical hypothalamic-hypophysis disorder, defined as an abnormally high level of prolactin (PRL) in blood (≥25 ng/ml for women and ≥20 ng/ml for men), and is a notable adverse effect of antipsychotic therapy [10], [12]. Antipsychotic-enhanced PRL secretion correlated with the acute and chronic dopamine (DA)-blocking actions [9]. Although DA agonists such as bromocriptine (BMT) are administrated for antipsychotic-induced high PRL [6], the side effects including aggravated psychosis and abnormal involuntary are a greater risk for patients than hyperPRL itself [6]. Identifying alternative therapy for hyperPRL is highly desired.
An herbal medicine formula Paeoniae-Glycyrrhiza Decoction (PGD) made from Paeonia (PR) and Glycyrrhiza radices (GR) has been introduced into the treatment in ovulation disorders, menopause and hyperPRL [18], [19], [23]. In our clinical trial, a great proportion of patients show improvements on risperidone-induced adverse effects associated with hyperPRL after PGD administration [23]. Further in vitro and in vivo experiments demonstrate that the hyper-level of PRL in MMQ cells and hyperprolactimia rat model is significantly reduced after PGD administration [22].
These encouraging results led us to further study the mechanisms underlying anti-hyperPRL effects of PGD in hyperprolactimia rat model. It is considered that pituitary PRL secretion is regulated mainly through the hypothalamic neuro-endocrine dopaminergic system [9]. Tyrosine hydroxylase (TH) is an enzyme that catalyzes the rate-limiting step of tyrosine conversion in the biosynthesis of DA, and is one of the targets of PRL action within the hypothalamus [2], [16]. In addition, dopamine transporters (DAT), responsible for re-uptaking of DA within hypothalamus, is also a component in the overall regulation of PRL homeostasis. D2 receptor (DRD2) shows an important effect on short-loop feedback mechanism of PRL regulation, and the robust PRL expression is observed in DRD2-null mice [4]. Moreover, progesterone (P) stimulates the production of deciduas PRL, conversely, it appears to be a potent inhibitor of myometrial PRL production [11].
In the present study, we examined the effects of PGD on the concentration of serum PRL and progesterone. The expression of DRD2, DAT and TH in pituitary gland and hypothalamus after PGD administration were determined. Our results revealed that PGD displayed anti-hyperPRL effects not only through the regulation of dopamine mediators, but also through the normalization of other sexual hormone dysfunction, including progesterone.
Section snippets
Herbal preparation
The raw materials of Paeoniae and Glycyrrhiza radices that constitute the PGD formula were supplied by the Pharmacy of School of Chinese Medicine in the University of Hong Kong (HKU). The extraction was conducted in an automatic boiling machine. Sliced, broiled Paeoniae and Glycyrrhiza radices (50 g each) were immersed and boiled in a 10-fold volume of distilled water for 2 h. This process was repeated twice as previously reported [22]. The extractive solution was pooled, concentrated, and
The effects of PGD and BMT on the related hormones in rat model of hyperPRL
PGD with doses of 2.5–10 g/kg or 0.6 mg/kg BMT were given to hyperPRL rats for 14 days. Animal bodyweight was unchanged over a period of treatment with either PGD or BMT (Fig. 1A). The significant differences were observed in response to serum concentration of PRL (P = 0.011) and progesterone (P = 0.018) treatment (Fig. 1B and C). For PRL, MCP chronic treatment resulted in an 88.1% elevation of PRL level compared to control group. PGD at doses of 5 g/kg and 10 g/kg and 0.6 mg/kg BMT significantly
Discussion
In clinical trial, a great proportion of patients showed improvements on risperidone-induced adverse effects associated with hyperPRL during PGD administration [23]. In vitro experiments demonstrated that PGD suppressed PRL release and synthesis in MMQ cells mediated by dopamine system [22]. In the present study, in vivo experiment was further performed in hyperPRL female rat model.
As described previously, DRD2 contributes to PRL regulation in short-loop feed back mechanism [5]. The increment
Conflict of interest
The authors have declared that there is no conflict of interest.
Acknowledgements
This study was supported by Health and Health Service Research Fund (HHSRF) in Hong Kong (Reference No.: 9101141) and General Research Fund (GRF) of Research Grant Council of HKSAR in Hong Kong (Reference No.: 785813).
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