Action mechanism of Zuo Gui Yin Decoction's promotion on estradiol production in rats during the peri-menopausal period.
OBJECTIVE
Although Zuo Gui Yin Decoction has long been used in Traditional Chinese Medicine to treat menopausal symptoms, the underlying mechanism(s) by which these effects are induced remains to be defined. The aim of this study was to investigate the action mechanism of Zuo Gui Yin Decoction on estradiol production in the rat ovary during peri-menopause.


METHODS
The peri-menopausal animal model was established by natural aging. Peri-menopausal rats were treated by intragastric administration (ig) with low (13.78gkg(-1)), middle (20.67gkg(-1)) or high (31gkg(-1)) dose of Zuo Gui Yin Decoction per day for 8 weeks. At the 8th weekend, the rats were sacrificed for sampling. Estradiol (E(2)) levels in rats' serum were evaluated by radioimmunoassay (RIA). RT-PCR, in situ hybridization and immunohistochemistry were used to determine mRNA and protein expression of relevant genes.


RESULTS
Medium- and high-dose of Zuo Gui Yin Decoction could significantly increase serum estradiol concentration, ovarian CYP19 mRNA levels, and P450(arom) protein expression in rats during peri-menopause. Zuo Gui Yin Decoction at three different dosages all could promote FSHR expression and the effect of low-dose was the greatest. Zuo Gui Yin Decoction could elevate LRH-1 and ER(α) expression in a dose dependent manner.


CONCLUSIONS
Taken collectively, these findings suggest that Zuo Gui Yin Decoction could promote estradiol production in rat serum during peri-menopausal period through ovarian ER(α)→LRH-1→CYP19 pathway as well as the ovarian classical FSHR→CYP19 mechanism.
Laboratory of Reproductive Endocrinology, Department of Physiology, Harbin Medical University, Harbin 150081, Hei Longjiang Province, China.
Wei
W
Zhao
Hai-Xia
HX
Wen
Hui-Li
HL
Zheng
Shi-Xiao
SX
Sun
Dian-Jun
DJ
Sun
Jiang
J
Ni
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008516:Medicine, Chinese Traditional; D010053:Ovary / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation
D017931:DNA Primers; D004958:Estradiol