The Biological Basis And Complications Of 'Phlegm Affected Baogong'(4)

Polycystic ovary syndrome is a common female internal secretion disease. It not only appears as an endocrine disease and also is a reproductive barrier. It is found out that polycystic ovary syndrome is closely related to insulin resistance. However, all existing researches concentrate to insulin function target organization, including skeletal muscles, fat and liver except ovary. It is inaccurate to assume that ovary function barrier is due to low insulin blood sickness barrier. Moreover, ovary junction barrier only exists in multi-pouches ovary syndrome patient, but not common in Type 2 diabetic patients. The glycometabolism of polycystic ovary syndrome patient is exceptionally related to insulin resistance and ovary function barrier. Ovary is the fundamental function unit of female reproduction. It involves insulin and signal protein and metabolism enzymes. Therefore this research has been established in vitro ovary insulin resistance model. It expresses the gonadotrophic hormone signal conduction and the insulin signal conduction in reciprocity.ObjectiveTo explore the direct contribution of insulin resistance in thecal cells to androgen excess and partial improvement by insulin sensitizers, namely berberine(Ber) and puerarin (Pue).MethodsOvarian theca cells from porcine follicles were isolated and cultured in vitro. Insulin resistance was induced in theca cells by dexamethasone (Dex) treatment for 48h, and evaluated by medium glucose contents or uptake of [~3H] labeled glucose of cultured cells. Insulin-resistant or control (Con) cells were further treated by Ber, Pue, or vehicle (Veh) respectively for further more 48h, and were analyzed with regards to medium glucose and testosterone, as well as the cellular expression of key insulin signal molecules by RT-PCR and western blotting.Results(1) Dex treated cells had significant lower [~3H]-glucose uptake(1077±78 cpm/10~6cells vs. 565±58 cpm /10~6cells, p< 0.05), but higher medium glucose (16.31±0.39 nmol/L vs. 10.62±1.02 nmol/L, p< 0.05), and testosterone(0.38±0.01μg/mL vs 0.82±0.20μg/mL, p< 0.05) as compared with untreated cells, indicating establishment of insulin resistance and enhanced androgenic potentials in this steroidogenic cells.(2) As compared with vehicle treatment in insulin resistant cells, Tro and Met significantly reduced the medium glucose and testosterone levels, suggesting decrease in both insulin resistance and steroidogenesis in thecal cells(3) The RT-PCR and western blot results showed that two sensitizers elevated the mRNA expressions of insulin receptor substrate -1 and glucose transporter -4 levels, but reduced peroxisome proliferator-activated receptor -γand 17-hydroxylase expressions, the key enzyme for androgen synthesis.Conclusions(1) Insulin resistance induced by Dex could directly exaggerate androgenic potentials within the thecal cells from porcine ovaries, suggesting the involvement of this ovarian metabolic phenotype in the pathogenesis of androgen excess in PCOS.(2) The beneficial effects of two sensitizing agents on reproduction could result from the alleviation of insulin resistance and androgen synthesis commonly found in PCOS treatment, indicating a local role within polycystic ovaries.