neuropeptide-y and Hyperandrogenism

To evaluate the effect of rosiglitazone on insulin resistance and hyperandrogenism in polycystic ovary syndrome (PCOS).. Rosiglitazone was given 4 mg daily to 30 patients with PCOS for 12 weeks. Before and after treatment, body mass index (BMI), plasma glucose, insulin, levels insulin resistance index (HOMA IR), blood lipid spectrum, leptin, neuropeptide Y, and sex hormone concentrations and ovulation rate were determined and compared.. After 12 weeks of treatment, basal insulin level decreased from (18 +/- 8) to (12 +/- 7) mIU/L (P < 0.01), HOMA IR decreased from 4.3 +/- 1.2 to 2.6 +/- 0.7 (P < 0.01). Luteinizing hormone, free testosterone and androstenedione levels decreased [(15.4 +/- 4.4) versus (7.9 +/- 2.1) U/L, (12.5 +/- 1.9) versus (8.9 +/- 1.4) pmol/L, (9.8 +/- 1.7) versus (7.4 +/- 1.2) nmol/L respectively, P < 0.01]; Dehydroepiandrosterone sulfate level also decreased [(8.7 +/- 3.5) versus (6.9 +/- 2.1) micromol/L, P < 0.05]; Sex hormone binding globulin level increased [(39 +/- 3) versus (58 +/- 5) nmol/L, P < 0.01]. Plasma leptin level was decreased [(18 +/- 4) versus (13 +/- 3) microg/L, P < 0.01]. Ovulation rate increased to 50%.. Rosiglitazone might decrease plasma leptin level and improve insulin sensitivity, which led to alleviation of hyperandrogenism and resumption of ovulation and menses in patients with PCOS.

Topics: Administration, Oral; Adult; Androstenedione; Blood Glucose; Body Weight; Female; Follicle Stimulating Hormone; Humans; Hyperandrogenism; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Lipids; Luteinizing Hormone; Menstruation; Neuropeptide Y; Ovulation; Polycystic Ovary Syndrome; Rosiglitazone; Testosterone; Thiazoles; Thiazolidinediones; Treatment Outcome

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder characterized by high androgen levels. The aim of this study was to evaluate the effects of hyperandrogenism on the hypothalamus and subsequently on the food intake and obesity in females.. A dihydroxy testosterone (DHT)-induced rat model was established to recapitulate the hyperandrogenism features of PCOS patients. Body weight and food intake of the rats were recorded. The food intake of DHT-induced rats was restricted by pair feeding to exclude possible effects of weight gain on the hypothalamus. The expression levels of relevant proteins and mRNAs in the hypothalamus and primary hypothalamic neurons exposed to DHT were analyzed by Western blotting and RT-PCR, respectively. The leptin levels in the serum and cerebrospinal fluid (CSF) were measured, and leptin was injected via the intracerebroventricular (ICV) route to test the leptin sensitivity of the hypothalamus.. The excessive prepuberty androgen levels in the DHT-induced rats markedly elevated food intake prior to weight gain. Consistent with this, the expression of neuropeptide Y and agouti-related peptide mRNAs was upregulated, which occurred prior to obesity and even with restricted food intake. In addition, the hypothalamic sensitivity to insulin and leptin was also impaired in the DHT-induced rats before obesity and with restricted food intake. DHT significantly reduced the leptin levels in the CSF, and ICV injection of leptin inhibited the DHT-induced increase in food intake.. Androgen excess increased food intake in rats and promoted obesity by downregulating insulin and leptin signaling in the hypothalamus, most likely by suppressing leptin levels in the CSF.

Topics: Androgens; Animals; Body Weight; Eating; Female; Humans; Hyperandrogenism; Hypothalamus; Insulin; Leptin; Neuropeptide Y; Obesity; Polycystic Ovary Syndrome; Rats; RNA, Messenger; Signal Transduction; Testosterone; Weight Gain

Five to ten percent of women of reproductive age suffer from polycystic ovary syndrome (PCOS). Leptin, NPY, galanin, cholecystokinin (CCK) are involved in the regulation of eating behavior. PPARγ are receptors that are probably involved in hyperandrogenism. This study was designed to assess associations between the Pro12Ala PPARγ2 gene polymorphism and satiety factors in PCOS. Fifty-four PCOS women and 51 healthy women were studied. Leptin, NPY, galanin, CCK levels, and genetic studies to detect Pro12Ala PPARγ2 gene polymorphism were assessed. The leptin levels in the PCOS women carrying Pro12Ala genotype were higher than in those with Pro12Pro and Ala12Ala. The PCOS women had higher leptin and NPY levels and lower galanin levels. Obese PCOS patients had lower CCK levels.. In the PCOS women, a single Ala allele may have a protective role as far as hyperleptinemia is concerned. The PCOS women may reveal a disrupted central leptin/NPY feedback loop with some shifts in food intake.

Topics: Adult; Body Mass Index; Cholecystokinin; Female; Galanin; Genotype; Humans; Hyperandrogenism; Insulin Resistance; Leptin; Neuropeptide Y; Obesity; Polycystic Ovary Syndrome; Polymorphism, Genetic; PPAR gamma; Satiation