phenanthrenes and Polycystic-Ovary-Syndrome

Polycystic ovary syndrome (PCOS) is a complex heterogeneous disorder characterized by androgen excess and ovulatory dysfunction; it is now known to be closely linked to metabolic syndrome. Recent research suggests that insulin resistance plays an important role in the pathogenesis of PCOS which may lead to the excessive production of androgens by ovarian theca cells. Currently there is no single drug that can treat both the reproductive and metabolic complications of the disorder. Existing pharmaceutical agents such as hormonal therapies have been associated with side effects and are not appropriate for PCOS women with infertility. Additionally, insulin sensitizing agents useful for treating the metabolic abnormalities in PCOS have limited efficacy for treating reproductive aspects of the disorder. Chinese herbal medicines have a long history of treating gynaecological problems and infertility and therefore may be a novel approach to the treatment of PCOS. Current research demonstrates that the compounds isolated from herbs have shown beneficial effects for PCOS and when combined in an herbal formula can target both reproductive and metabolic defects simultaneously. Therefore, further investigation into Chinese herbal medicine in the treatment of PCOS is warranted.

Topics: Androgens; Berberine; Drugs, Chinese Herbal; Female; Ginsenosides; Glucosides; Humans; Insulin Resistance; Monoterpenes; Phenanthrenes; Phytotherapy; Polycystic Ovary Syndrome; Resveratrol; Stilbenes; Theca Cells

Topics: Animals; Apoptosis; Female; Ferroptosis; Humans; Inflammation; Matrix Metalloproteinases; Membrane Potential, Mitochondrial; Oxidative Stress; Phenanthrenes; Polycystic Ovary Syndrome; Rats

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies and primarily presents with hyperandrogenism. Although environmental factors and genetic factors are thought to be the major reason, there still exists a lot of questions need to be answered. High expression of C‑terminal‑binding protein 1 antisense (CTBP1‑AS) was identified as an independent risk factor for PCOS; however, the molecular mechanism of CTBP1‑AS in PCOS regulation is unknown. In the present study, the expression level of CTBP1‑AS was found to be significantly upregulated in patients with PCOS compared with healthy control patients. CTBP1‑AS knockdown was demonstrated to reduce the proliferation and promote the apoptosis of granulosa tumor cells

Topics: Alcohol Oxidoreductases; DNA-Binding Proteins; Female; Humans; Phenanthrenes; Polycomb Repressive Complex 2; Polycystic Ovary Syndrome; RNA, Antisense; Transcriptional Activation; Up-Regulation

Cryptotanshinone (CRY) has been demonstrated to reverse reproductive disorders. However, whether CRY is effective in the treatment of polycystic ovary syndrome (PCOS) remains unknown. The aim of the present study was to evaluate the therapeutic potential of CRY in PCOS. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. Total body weight and ovarian weight, as well as the levels of luteinizing hormone (LH) and the LH to follicle‑stimulating hormone (FSH) ratio (LH/FSH) significantly increased in rats with PCOS, compared with controls. Moreover, the levels of testosterone (T), tumor necrosis factor (TNF)‑α and high‑mobility group box 1 protein (HMGB1) also increased. However, CRY treatment attenuated the increase in body weight, ovarian weight, LH, LH/FSH ratio, T, TNF‑α and HMGB1 levels, compared with the PCOS group. Treatment with CRY also reduced NF‑κB/p65, HMGB1 and toll‑like receptor (TLR)4 mRNA and protein expression levels in the ovarian tissue and granulosa cells, both in vitro and in vivo. Thus, CRY significantly mitigated the changes in body weight, ovary weight, hormone levels and inflammatory factor levels observed in rats with PCOS. Thus, CRY protects against PCOS‑induced damage of ovarian tissue, possibly through a regulatory pathway involving HMGB1, TLR4 and NF‑κB.

Topics: Animals; Body Weight; Cell Proliferation; Cell Survival; Disease Models, Animal; Female; Gene Expression Regulation; HMGB1 Protein; NF-kappa B; Organ Size; Phenanthrenes; Polycystic Ovary Syndrome; Rats; Signal Transduction; Toll-Like Receptor 4

To investigate the effects of cryptotanshinone (CRY), an active component of Chinese medicine, on ovarian androgen production, insulin resistance (IR), and glucose metabolism in mice.. Animal model and in vitro tissue model.. University-affiliated laboratory.. Mice.. Ovarian IR was induced by dexamethasone (DEX) in vivo. Animals were randomized to receive CRY treatment for 3 days or not. Ovulation rates, serum steroid levels, and glucose uptake in ovaries were quantified, and proteins in the phosphatidylinositol 3-hydroxy kinase pathway were measured. In vitro ovarian IR was also induced by DEX for 3 days. Ovarian steroid hormone secretion and glucose uptake were measured, and the hormone-synthesizing enzymes were determined by semiquantitative reverse transcription-polymerase chain reaction.. Ovarian glucose uptake, in vivo ovulation rate, serum and culture medium steroid level, and molecular expression of phosphatidylinositol 3-hydroxy kinase and steroidogenic enzymes.. Dexamethasone significantly increased ovulation rates in vivo and increased T and E2 production and decreased ovarian glucose uptake in vivo and in vitro. Cryptotanshinone significantly reduced ovulation rates in vivo and decreased T and estrogen production in vitro. Cryptotanshinone attenuated the inhibition of DEX on AKT2 and suppressed the up-regulation of CYP11 and CYP17 expression by DEX.. Cryptotanshinone reversed DEX-induced androgen excess and ovarian IR in mice through activation of insulin signaling and the regulation of glucose transporters and hormone-synthesizing enzymes. This suggests a potential role for CRY in treating the ovulatory dysfunction associated with PCOS.

Topics: Animals; Blood Glucose; Dexamethasone; Disease Models, Animal; Estradiol; Female; Gene Expression Regulation, Enzymologic; Glucose Metabolism Disorders; Glucose Transport Proteins, Facilitative; Insulin; Insulin Resistance; Mice; Ovary; Ovulation; Phenanthrenes; Phosphatidylinositol 3-Kinase; Polycystic Ovary Syndrome; Proto-Oncogene Proteins c-akt; Signal Transduction; Steroid 17-alpha-Hydroxylase; Testosterone; Tissue Culture Techniques

This trial explores 1) prenatally androgenized (PNA) rats as a model of polycystic ovary syndrome (PCOS) and 2) reproductive and metabolic effects of cryptotanshinone in PNA ovaries. On days 16-18 of pregnancy, 10 rats were injected with testosterone propionate (PNA mothers) and 10 with sesame oil (control mothers). At age 3 mo, 12 female offspring from each group were randomly assigned to receive saline and 12 cryptotanshinone treatment during 2 wk. Before treatment, compared with the 24 controls, the 24 PNA rats had 1) disrupted estrous cycles, 2) higher 17-hydroxyprogesterone (P = 0.030), androstenedione (P = 0.016), testosterone and insulin (P values = 0.000), and glucose (P = 0.047) levels, and 3) higher areas under the curve (AUC) for glucose (AUC-Glu, P = 0.025) and homeostatic model assessment for insulin resistance (HOMA-IR, P = 0.008). After treatment, compared with vehicle-treated PNA rats, cryptotanshinone-treated PNA rats had 1) improved estrous cycles (P = 0.045), 2) reduced 17-hydroxyprogesterone (P = 0.041), androstenedione (P = 0.038), testosterone (P = 0.003), glucose (P = 0.036), and insulin (P = 0.041) levels, and 3) lower AUC-Glu (P = 0.045) and HOMA-IR (P = 0.024). Western blot showed that cryptotanshinone reversed the altered protein expressions of insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase p85α, glucose transporter-4, ERK-1, and 17α-hydroxylase within PNA ovaries. We conclude that PNA model rats exhibit reproductive and metabolic phenotypes of human PCOS and that regulation of key molecules in insulin signaling and androgen synthesis within PNA ovaries may explain cryptotanshinone's therapeutic effects.

Topics: 17-alpha-Hydroxyprogesterone; Androgens; Androstenedione; Animals; Drugs, Chinese Herbal; Female; Glucose; Insulin; Insulin Resistance; Models, Animal; Ovary; Phenanthrenes; Polycystic Ovary Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Reproduction; Signal Transduction; Testosterone

To study the effects of cryptotanshinone on androgen synthesis for the prenatally androgenized male rats.. On days 16-18 of pregnancy, rats were injected s. c. with testosterone propionas continuously for 3 days; male offspring were studied as subject. Serum concentrations of testosterone (T), 17a-hydroxy progesterone (17-OHP), blood glucose, and insulin were measured by radioimmunoassay. Then, the rats were treated with cryptotanshinone by gavage for 14 days, and the levels of serum T, 17-OHP and insulin were detected and the 17a-hydroxylase protein expression in interstitial cell was measured using the method of immunohistochemistry.. There was no difference between the male groups who were prenatally androgenized in serum levels of T, but the 17-OHP, fasting insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) elevated significantly (P < 0.05). Cryptotanshinone could lower the levels of 17-OHP (P < 0.05) but had no effect on 17a-hydroxylase.. Prenatally androgenized male rats exhibit elevated 17-OHP and diminished insulin sensitivity. Cryptotanshinone could decrease 17-OHP, but has no effect on insulin, indicating it may reduce androgen synthesis.

Topics: Androgens; Animals; Disease Models, Animal; Female; Humans; Male; Maternal Exposure; Phenanthrenes; Polycystic Ovary Syndrome; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Rats; Rats, Wistar