Humanin Alleviates Insulin Resistance in Polycystic Ovary Syndrome: A Human and Rat Model-Based Study.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism and insulin resistance (IR); however, the pathogenesis of local ovarian IR in PCOS remains largely unclear. Humanin, a mitochondria-derived peptide, has been reported to be associated with IR. Our previous study confirmed that humanin is expressed in multiple cell types in the ovary and is present in follicular fluid. However, it remains unknown whether humanin participates in the pathogenesis of local ovarian IR or whether humanin supplementation can improve IR in PCOS patients. In this study, we compared humanin concentrations in follicular fluid from PCOS patients with and without IR. We further investigated the effect of humanin analogue (HNG) supplementation on IR in a rat model of dehydroepiandrosterone-induced PCOS. Humanin concentrations in the follicular fluid were found to be significantly lower in PCOS patients with IR than in those without IR. HNG supplementation attenuated both the increases in the levels of fasting plasma glucose and fasting insulin in rats with PCOS and the decreases in phosphorylation of IRS1, PI3K, AKT, and GLUT4 proteins in the granulosa cells of these rats. Combined supplementation with HNG and insulin significantly improved glucose consumption in normal and humanin-siRNA-transfected COV434 cells. In conclusion, downregulated humanin in the ovaries may be involved in the pathogenesis of IR in PCOS, and exogenous supplementation with HNG improved local ovarian IR through modulation of the IRS1/PI3K/Akt signaling pathway in a rat model. This finding supports the potential future use of HNG as a therapeutic drug for PCOS.

Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway.

Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, whereas the pathogenesis is still not fully understood. Systemic and ovarian oxidative stress (OS) imbalance is a pivotal feature of PCOS. Humanin, a mitochondria-derived peptide, has been reported to function as an antioxidant in cardiomyocytes, pancreatic beta cells and other cells, but how this function is regulated remains unclear. In this study, we investigated whether humanin expression differs in the granulosa cells (GCs) of PCOS patients versus controls, and whether humanin alleviates OS in PCOS ovaries. Sixteen PCOS patients and 28 age- and BMI-matched controls undergoing IVF were recruited, and their serum, follicular fluid and GCs were collected for humanin analysis. Dehydroepiandrosterone-induced rat PCOS models, and vitamin K3-induced OS COV434 cell lines were applied to investigate the mechanism. Humanin expression was significantly down-regulated in the ovaries of PCOS patients relative to those of non-PCOS patients. Exogenous humanin supplementation significantly attenuated body weight gain, ovarian morphological abnormalities, endocrinological disorders and ovarian and systemic OS in PCOS rat models. Our study further demonstrated that this attenuation effect was involved in the modulation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. In summary, this study reported for the first time that decreased expression of humanin in the GCs was associated with oxidative imbalance in PCOS. Humanin alleviates OS in ovarian GCs of PCOS patients via modulation of the Keap1/Nrf2 signalling pathway.

Efficacy of combined traditional Chinese medicine spray with premature ejaculation desensitization therapy for the treatment of primary premature ejaculation.

OBJECTIVES: We recommend a new kind of spray made from eight kinds of traditional Chinese medicine, we aimed to investigate the safety and clinical efficacy of combined traditional Chinese medicine spray (TCMS) with premature ejaculation desensitization therapy (PEDT) for the treatment of primary premature ejaculation (PPE). METHODS: A total of 90 patients with PPE were randomly assigned to receive TCMS, PEDT monotherapy or TCMS plus PEDT combination therapy for 6 weeks. Intravaginal ejaculation latency time (IELT) and Chinese index of sexual function for premature ejaculation (CIPE-5) were measured to evaluate the effect of each treatment. RESULTS: Eighty six (86) participants completed the study voluntarily. Both IELT and CIPE-5 in these three groups increased after treatment when compared with baseline levels (p< 0.01). IELT and CIPE-5 after treatment in TCMS plus PEDT group were significantly higher than those in the other two groups (both p <0.05). Additionally, clinical efficacy in TCMS plus PEDT group (89.7%) was significantly higher than in TCMS (65.5%) and PEDT group (67.9%) (p< 0.01). CONCLUSION: The self-made TCMS was safe and effective for the treatment of PPE, a combination of TCMS and PEDT therapy was more effective than the TCMS or PEDT monotherapy.

Effects of antisense oligodeoxynucleotide to follicle-stimulating hormone receptor on the cell proliferation and apoptosis in cells derived from human ovarian mucinous cystadenocarcinoma in Vitro.

The human ovarian mucinous cystadenocarcinoma (hOMC) cells were co-cultured with antisense oligodeoxynucleotide (antisense ODN), nonsense ODN, and follicle-stimulating hormone (FSH) at different concentrations for the purpose of observing the effects of antisense ODN to FSH receptor (FSHR) on the proliferation and apoptosis of cultured hOMC cells in vitro. The inhibitory rates of growth were measured by using MTT method on the 2nd, 4th, 6th, 8th and 10th days after the interference of antisense ODN, nonsense ODN, and FSH, respectively. The apoptotic rates and the cell cycles were determined by means of flow cytometry, the apoptosis indexes were detected by using TUNEL, and the expression of caspase-3 was measured by using SP immunohistochemistry. Compared with that in the control group, the proliferative activity of hOMC cells was increased obviously in FSH groups (P<0.05 or P<0.01), decreased distinctly in antisense ODN groups (P<0.05 or P<0.01), and unchanged in nonsense ODN groups, respectively. Meanwhile, antisense ODN could significantly antagonize the FSH-promoted cell proliferative activity (P<0.01). Compared with those in the control group, the apoptotic rates and the expression of caspase-3 were dramatically increased in the mid-and high-dose antisense ODN groups (P<0.05 or P<0.01), while the number of cells in G(1)/G(0) phase was significantly decreased and that in S phase distinctly increased (P<0.01). There was no change in nonsense ODN groups (P>0.05). It was suggested that FSH may improve the development of hOMC cells. However, antisense ODN could inhibit proliferative activity and the FSH-promoted proliferative activity in hOMC cells, at the same time, antisense ODN could inhibit hOMC cell growth by inducing apoptosis.

[Effect of eucommia ulmoides oliv on SOD activity and alpha-actin expression in the penile tissues of diabetic rats].

OBJECTIVE: To study the effect of aqueous abstract from eucommia ulmoides oliv on the activity of superoxide dismutase (SOD) and alpha-actin expression in the penile tissues of rats with diabetes mellitus (DM) in vitro. METHODS: A diabetes model was established by administration of alloxun twice to Sprague Dawley (SD) rats. Ten diabetic and 10 normal rats were randomly selected and the penile strips of each rat were divided into four equal shares and cultured in two groups, a eucommia ulmoides oliv coculture group (Group A, further dicided into 1 microg/ml, 10 microg/ml and 100 microg/ml subgroups) and a control group (Group B). Seven days later, the activity of SOD in the culture medium was detected by spectrophotometry, and the levels of micro-actin expression in the penile tissues were examined with the immunohistochemical method. RESULTS: Compared with Group B, the activity of SOD in the culture medium in athe 10 and 100 microg/ml subgroups was notably elevated (P < 0.01), and the numbers of immunoreactive positive cells of alpha-actin in the penile tissues remarkably increased (P < 0.01). CONCLUSION: The activity of SOD and alpha-actin expression in the penile tissues of diabetic rats in vitro can be increased by eucommia ulmioides oliv.