Akt-mTOR Signaling Mediates Abnormalities in the Proliferation and Apoptosis of Ovarian Granulosa Cells in Patients with Polycystic Ovary Syndrome.

BACKGROUND/AIMS: Abnormal apoptosis of granulosa cells (GCs) is thought to involve in the pathogenesis of polycystic ovary syndrome (PCOS); however, the associated cellular and molecular mechanisms remain unclear. METHODS: Primary GCs were obtained from healthy women and women with PCOS. The cell proliferation and apoptosis were analyzed in insulin-stimulated and insulin receptor gene (INSR) siRNA-transfected GCs. The protein expression of Akt-mTOR-S6K1 signal molecules was measured by Western blot. RESULTS: This study showed that 1 nM of insulin significantly stimulated cell proliferation, induced cell apoptosis, and decreased the telomerase activity in GCs from both the healthy women and PCOS patients (p < 0.001), but silencing of INSR expression blocked the effects of insulin. Insulin induced significantly more apoptosis in GCs from PCOS patients than from healthy women (p < 0.01). Insulin significantly increased the ratio of p-Akt/Akt, the expression of mTOR protein, and the ratio of p-S6K1/S6K1 in GCs from normal control than in cells from PCOS patients (p < 0.001). CONCLUSION: Insulin-induced apoptosis of GCs, less activation of Akt-mTOR signaling, and reduction of telomerase activity may be associated with the pathogenesis of PCOS.

[Survey on characteristics of menopause of Chinese women with the age of 40-60 years at gynecological clinic from 14 hospitals].

OBJECTIVE: To investigate the characteristics of menopause of Chinese women with the age of 40-60 years concerning gynecologic clinics in China. METHODS: From Mar.2008 to Sept.2008, a face-to-face questionnaire was conducted in gynecological clinic in perimenopausal and postmenopausal women in 14 hospitals in China, which included general demographic data, menstrual change process, climacteric symptoms and knowledge about menopause. Modified Kupperman index were used to evaluate climacteric symptoms during the recent week and awareness of hormonal replacement therapy were studied. RESULTS: A total of 1641 women were investigated. The ages of onset of menopause transition, climacteric symptoms and natural menopause were (47 ± 4), (46 ± 4), (49 ± 3) years old respectively. Climacteric symptoms could be found in 78.43% (1287/1641) women during menopausal transition, which were mainly mild to moderate symptoms. The top 5 symptoms were fatigue and weakness (71.48%, 1173/1641), irritability (68.68%, 1127/1641), insomnia (67.65%, 1110/1641), muscle and joint pain (64.11%, 1052/1641) and hot flush (57.90%, 950/1641). The climacteric symptoms were not constant during menopausal transition, usually more severe in late transition and postmenopausal periods, during which the moderate and severe symptoms were 59.1% (189/320) and 51.1% (291/570) respectively. Although most symptoms primarily appeared along with menstruation change, there are about 17.5% (172/981) patients experienced climacteric symptoms before menstruation change occurrence. There were 56.39% (733/1300) women had ever heard (mostly from gynecologist) about hormone replacement therapy from Obstetrician and Gynecologist. CONCLUSIONS: Most of the women during menopausal transition had climacteric symptoms, usually mild and moderate ones. Although most symptoms primarily appeared along with menstruation change, there are other patients' experienced climacteric symptoms before menstruation change occurrence.

[Spontaneous abortion and changes of estrogen receptors and progesterone receptors in the endometria of patients with polycystic ovary syndrome].

OBJECTIVE: To explore the relationship between the spontaneous abortion and changes of estrogen receptors (ER) and progesterone receptors (PR) in the endometria of patients with polycystic ovary syndrome (PCOS). METHODS: Thirty-two patients who suffered PCOS combined with infertilitas feminis were enrolled in a experimental group,and 20 patients with tubal infertilitas feminis having the corresponding time period as a control group. The expressions of ER and PR in the endometria were observed by pathological examination and immunohistochemical staining. RESULTS: The expressions of ER and PR in the glands and interstitium of endometrial in the PCOS group were significantly lower than those of the tubal infertilitas feminis group (P=0.004,P=0.001). The expressions of ER and PR in the PCOS group in the glands organ and interstitium of endometrial among 3 different periods were not significantly different (P>0.05). The expressions of ER in the glands of endometrium in the spontaneous abortion group were significantly lower than those of the non-spontaneous abortion group (P=0.02), but there was no statistical difference between the two groups in the interstitium of endometria (P>0.05). The expression of PR in the glands interstitium of endometria showed no statistical difference between the spontaneous abortion group and the non-spontaneous abortion group (P>0.05). CONCLUSION: The decrease of ER and PR of endometrial in the PCOS patients, may be a reason for spontaneous abortion, and the cyclical irregularity of ER and PR in the PCOS patients is another cause of spontaneous abortion.

[Clinical analysis of 4 treatments for woman polycystic ovarian syndrome with infertility].

OBJECTIVE: To investigate the therapeutic effects of 4 different treatments for woman polycystic ovarian syndrome (PCOS) with infertility. METHODS: One hundred and twenty women PCOS with infertility were divided into 4 Groups : patients in Group 1 were directly treated with clomiphene (CC)/CC + human menopausal gonadotropin (HMG) + human chorionic gonadotropin (HCG) to accelerate ovulation; patients in Group 2 were treated with the same way as Group 1 after taking marvolon for 2 cycles; patients in Group 3 took marvolon for 2 cycles and metformin for 8 weeks, and then were treated the same as Group 1; patients in Group 4 were treated with laparosocopy. The body mess index (BMI), emmenia period, weight, volume of ovary, LH, and T were measured before and after the treatment in all patients. The cycle ovulatory rate and occurrence rate of luteinized unruptued follicle syndrome (LUFS) within 2 months and the pregnancy rate within 6 months after the treatment were also observed. RESULTS: In all patients, BMI, emmenia period, serum T, and serum LH decreased significantly (P <0.05 or 0.01). The body mess indexes were significantly lower in Group 2 and Group 3 than those in Group 4 and Group 1, and Group 4 was also lower than Group 1 (P < 0.05 or 0.01). There was no difference in emmenia period between the 4 groups (P = 0.289). The volumes of ovary were enlarged in Group 1, and they were shrunk in the residual groups, which was significantly lower in Group 4 than in Group 2 and 3 (P < 0.01). The cycle ovulation rates were 53%, 72 %, 78 %, and 76%; the pregnancy rates within 6 months were 20%, 47%, 50%, and 57%, respectively; and they were significantly higher in the Group 2, 3 and 4 than in Group 1 (P <0.01). The occurrence rates of LUFS were 32%, 16%, 15%, and 13%, and they were significantly lower in Group 2, 3 and 4 than in Group 1 (P <0. 01). CONCLUSION: The effects of marvolon or marvolon and metformin are the same as those of laparoscopy not only in controlling the symptoms of PCOS, but also in increasing the cycle ovulation rate, pregnancy rate within 6 months, and decreasing the occurrence rate of LUFS. The symptoms of PCOS can be controlled better, but the cycle ovulation rate and pregnancy rate within 6 months can not be improved when clomiphene is used alone.