Prenatal Hyperandrogenization Induces Metabolic and Endocrine Alterations Which Depend on the Levels of Testosterone Exposure

Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in rats. The aim of the present study was to establish if the levels of prenatal testosterone may determine the extent of metabolic and endocrine alterations during the adult life. Pregnant Sprague Dawley rats were prenatally injected with either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to day 19 day of gestation. Female offspring from T2 and T5 displayed different phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism, ovarian cysts and ovulatory cycles whereas those from T5 displayed hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed increased circulating glucose levels after the intraperitoneal glucose tolerance test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats and directly correlated with body weight at prepubertal age. However, the decrease in the body weight at prepubertal age was compensated during adult life. Although both groups showed enhanced ovarian steroidogenesis, it appears that the molecular mechanisms involved were different. The higher dose of testosterone enhanced the expression of both the protein that regulates cholesterol availability (the steroidogenic acute regulatory protein (StAR)) and the protein expression of the transcriptional factor: peroxisome proliferator-activated receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti-oxidant response that prevented a possible pro-oxidant status. The higher dose of testosterone induced a pro-inflammatory state in ovarian tissue mediated by increased levels of prostaglandin E (PG) and the protein expression of cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our data show that the levels of testosterone prenatally injected modulate the uterine environment and that this, in turn, would be responsible for the endocrine and metabolic abnormalities and the phenotype of PCOS during the adult life

Effect of percutaneous balloon valvuloplasty on pulmonary hypertension in mitral stenosis.

Percutaneous mitral balloon valvuloplasty (PMBV) has been useful in decreasing mitral valve obstruction in mitral stenosis; however, the long-term effects of valvuloplasty on pulmonary artery pressure have not been extensively studied. Thirty-three patients underwent PMBV in our institution between January 1988 and December 1991. There were significant reductions in peak (19 +/- 1 to 12 +/- 1 mm Hg) and mean (10 +/- 0.7 to 6 +/- 0.4 mm Hg) mitral valve gradients estimated by Doppler techniques immediately after PMBV. The mitral valve area, as assessed by the pressure half-time method, increased from 1.06 +/- 0.05 to 1.98 +/- 0.08 cm2 (p \u3c 0.001) after the procedure and remained significantly greater (1.68 +/- 0.11 cm2) at 17 +/- 2 months. Right ventricular systolic pressure (RVSP) was estimated in patients with tricuspid regurgitation (TR) using the modified Bernoulli equation. There was a good correlation between Doppler and catheterization for RVSP (r = 0.83 pre valvuloplasty; r = 0.87 post valvuloplasty). Right ventricular systolic pressure by Doppler was 56 +/- 4 mm Hg before valvuloplasty and 48 +/- 4 mm Hg immediately afterwards (p \u3c 0.001). Nine patients had TR on follow-up Doppler studies with an estimated RVSP of 53 +/- 9 mm Hg (p = NS compared with pre- and post-valvuloplasty values). Six of these nine patients had moderate or severe mitral regurgitation (MR), compared with one patient without TR at follow-up (p \u3c 0.05). There appears to be a good correlation between the RVSP determined by Doppler and measured at catheterization.(ABSTRACT TRUNCATED AT 250 WORDS

Study of association of IRS-1 and IRS-2 genes polymorphisms with clinical and metabolic features in women with polycystic ovary syndrome. Is there an impact?

Objective.Insulin receptor substrate (IRS) proteins are critical to signal transduction in insulin target tissues. The present study was undertaken to determine whether IRS-1 Gly972Arg and IRS-2 Gly1057Asp influence hormonal and metabolic characteristics in Greek patients with polycystic ovary syndrome (PCOS) and controls. Material and methods.One hundred and eighty-three women with PCOS and 88 healthy volunteers were enrolled. Venous blood samples were obtained for genetic study and hormonal profile, glucose, and insulin assays, on days 3 to 7 from cycling patients. DNA was extracted by whole blood samples for genotyping and detection of IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms. Results.Fifty-six women with PCOS (30.60), whereas 12 women in the control group (13.64) carried the IRS-1 polymorphism (p0.0026). No statistically significant differences in genotypes or allele frequencies for IRS-2 polymorphism were observed between controls and PCOS women. No significant differences in any clinical or hormonal measures between subjects on the basis of genotype were observed, except the increased levels of fasting glucose that exhibit the carriers of the Asp allele of the IRS-2 polymorphism. Conclusions.Only the IRS-1 polymorphism is associated with increased susceptibility to PCOS in a Greek population. These loci should not be considered as major contributors to the hormonal and metabolic phenotype of PCOS. © 2010 Informa UK Ltd

Peroxisome proliferator-activated receptor-γ and -δ Polymorphisms in women with polycystic ovary syndrome

The aim of the study was to examine the frequency and relationship of peroxisome proliferator-activated receptor (PPAR)-γ and PPAR-δ gene polymorphisms to polycystic ovary syndrome (PCOS) characteristics. We conducted a case-control study protocol, which included 183 PCOS women and 148 healthy volunteers. Genetic, clinical, hormonal, and metabolic characteristics of PCOS patients and controls were estimated and compared. Genotype and allele frequencies did not differ significantly. The Pro12Ala polymorphism in exon 2 of the PPAR-γ gene was found in low frequency. Regarding the polymorphism in exon 6, the T-allele carrier PCOS women had significantly lower total testosterone levels. Regarding the +294TC polymorphism in the exon 4 of the PPAR-δ gene, the C-allele carrier PCOS women had significantly higher fasting glucose levels. In conclusion, the PPAR-γ gene polymorphisms do not appear to affect the risk for PCOS, except for the reduced testosterone levels. The +294TC polymorphism in the exon 4 of the PPAR-δ gene seems to cause an increase in fasting glucose levels. © 2010 New York Academy of Sciences