P450 Arom Expression In Polycystic Ovary Syndrome Rats

Objective: Making a model of PCOS rats, we can compare the P450 aromatase expression of PCOS rats and the normal ones, in their ovaries and uteruses, also in muscle and fat. Furthermore, we can probe into the effection of which two different administrator of arimedex (letrozole) while treating PCOS.Method: randomizing 80 SD rats of 42 days into 4 groups: group I---45 rats modeled in DHEA + Ins, group II---15 rats modeled in HCG + Ins, two corresponding control groups of 10 rats respectively. When the rats are at 70 days, we give them 20 days of continuous vaginal smear, observing the variation of their estrous cycle. While at 90 days, the degree of their T, E₂, P, LH, FSH, FPG, FINS in the serum should be determined, also the LH/FSH and Homa-IR. Selected 10 rats which have not regular estrous cycle, we excise their bilateral ovaries, one side with histological slice, and the other side used for the determination of mRNA in P450 aromatase. We also excise the muscle, fatty tissue and uterus, which are also used for the determination that we have mentioned above. Choosing the rats (PCOS rats) which are modeled successfully, we randomize them into two treating groups, group I---10 rats treated with intragastric administration of letrozole in the dosage of 1.4mg/100mg·d, group II---10 rats, the same treatment as group I, but in the dosage of 11mg/100mg·4d.Results: (1) There were 95.6 percent of rats losting regular estrous cycle in the model I and 93.3 percent of rats in the model II. The ovary weight of rats in both two models was heavier than that of controls. Rats of both two models showed polycystic ovary-like syndrome manifestation, The average saccular ovulas in model I (0.048±0.012) was smaller than those in model II (0.069±0.036), The number of corpora lutea in model I (0.10±0.32) was smaller than that in model II (0.70±0.82). Serum levels of T, LH/FSH increased in both two models,P decreased in both two models, Serum levels of E₂ had no significant increase (P>0.05). HOMA-IR of both two models were higher than that of controls with model I (8.89±0.86) significantly higher than model II (6.86±0.48). (2) While determining the amount of mRNA expression of P450 aromatase in the rats'muscle, we find out that the modeling group (0.42±0.04) is nearly as the same as its control group (0.38±0.04). In the rats'fat tissue, the modeling group (0.45±0.05) is also as the same as its control group (0.38±0.05). In the rats'ovary, the modeling group (2.80±1.19) is significantly higher than its control group (0.82±0.18). In the rats'uterus, the modeling group (1.83±0.40) is significantly higher than its control group (0.58±0.10). (3) After administration of the two treating groups, we can find out that the degrees of E₂ and P are significant higher than that before administration (P<0.05). The LH/FSH and FINS are significant lower than that before administration. T and FPG have no remarkable difference while compared with that before administration (P>0.05). We determined the T, E₂, P, LH, FSH in the serum, that of the treated group I have no significant difference with that of the treated group II (P<0.05), but the degree of HOMA-IR of the treated group I (4.51±0.35) are remarkable lower than that of the treated group II (5.11±0.43).Conclusion: (1) The model of DHEA+Ins is more similar to human PCOS in the morphology of ovary and the degree of insulin resistance,and it is more stable. (2) The amount of mRNA expression of P450 aromatase in rats'uteruses and ovaries would increase, if the PCOS rats are modeled in DHEA + Ins. The expression of P450 arom in PCOS rats is positive correlation with HOMA-IR. (3) Arimedex (letrozole) can induce the PCOS rats to ovulate effectively without the increasing of T. The different methods of administration have no influence on the serum endocrine, but the method of 1.4mg/100mg·d can lower the insulin resistance effectively.