The Common Follicle-Stimulating Hormone Receptor (FSHR) Promoter Polymorphism FSHR -29G > A Affects Androgen Production in Normal Human Small Antral Follicles.

Follicle-stimulating hormone receptors (FSHRs) are almost exclusively expressed on granulosa cells, and FSH action is probably most clearly reflected in intrafollicular hormone milieu of antral follicles. Little is known about the possible effects of the common single nucleotide polymorphism (SNP) FSHR -29G > A (rs1394205) on hormonal conditions in humsan small antral follicles (hSAFs) obtained from women in the natural menstrual cycle. This study investigated the follicle fluid (FF) concentrations of anti-Müllerian hormone, estradiol, progesterone, androstenedione, and testosterone in hSAF in relation to the different genotypes of FSHR -29G > A. FF from 362 follicles was collected in 95 women undergoing fertility preservation, who did not suffer from a disease that directly affected ovarian function. The testosterone levels of the minor A/A genotype were significantly increased compared to the A/G and the G/G genotype. Furthermore, significantly reduced androstenedione levels were observed for the G/G genotype, as compared to the A/G genotype, while the other hormones did not show statistical significant differences. In conclusion, the androgen levels of hSAF were significantly elevated in the minor SNP genotype in the FSHR promoter polymorphism FSHR -29G > A.

Influence of concomitant heparin administration on pregnancy-associated plasma protein-A levels in acute coronary syndrome with ST segment elevation.

INTRODUCTION: The time course of pregnancy-associated plasma protein-A (PAPP-A) levels was studied at admission, immediately after percutaneous coronary intervention (PCI) and 1, 2, 4, 6, 12, 24 and 48 h after PCI in acute coronary syndrome with ST segment elevation (ACS-STE) to determine the impact of PCI, concomitant clinical complications and heparin administration. MATERIAL AND METHODS: Pregnancy-associated plasma protein-A serum levels, examined by the Kryptor(TM) system, were studied in 30 heparinized PCI ACS-STE patients, in 10 elective PCIs and 12 coronary angiographies with heparin, and in 5 patients with normal coronary angiogram without heparin. RESULTS: Heparin caused a high PAPP-A increase in ACS-STE patients, in all patients with heparin without ACS and angiographic signs of significant atherosclerosis. This increase was directly associated with heparin dosage and activated clotting time (ACT) (r = 0.71, p = 0.0001) and inversely with the interval between heparin applications and time of serum sampling. It was followed by a rapid decrease within 1 to 2 h and return to normal levels in 10 to 12 h. In ACS-STE patients the decrease was significantly slower than in heparinized elective PCI and angiography patients. The PAPP-A increase was not significantly dependent on the length of PCI. Persistent increase after 24 h was associated in 4/7 patients with concomitant clinical complications. CONCLUSIONS: The diagnostic validity of PAPP-A can be verified only within the 1(st) h after clinical onset of ACS before heparin administration, the prognostic value in heparinized patients not earlier than 12 h after the last heparin application, if ACT is normal and serious clinical concomitant complications are eliminated.

Renal effects of HMG-CoA reductase inhibition in a rat model of chronic inhibition of nitric oxide synthesis.

BACKGROUND/AIMS: In addition to their lipid-lowering effects, HMG-CoA reductase inhibitors (statins) induce a variety of pleiotropic actions that have been recently studied in the area of cardiovascular and renal protection. In the present studies we sought to determine whether statins retain beneficial effects in the experimental model of NO deficiency achieved by chronic administration of a pressor dose of L-arginine analogue N-nitro-L-arginine-methyl ester (L-NAME). METHODS: To address this issue, blood pressure (BP), renal function (GFR), and albuminuria were determined in rats treated for 4 weeks with L-NAME, L-NAME + atorvastatin (ATO), and in untreated controls. In addition, renal cortical protein expression of caveolin 1 (CAV1), vascular endothelial growth factor (VEGF), and activity of RhoA were also determined. RESULTS: L-NAME administration resulted in sustained elevation of BP, decreased GFR, and in higher albuminuria as compared to control animals. Co-administration of ATO with L-NAME normalized albuminuria and prevented decreases in GFR in L-NAME rats without having an impact on pressor effects of L-NAME. CAV1 protein expression was similar in all groups of rats. In contrast, VEGF expression and RhoA activity was increased in L-NAME-treated animals, and normalized with co-administration of ATO. CONCLUSION: Treatment with ATO exerts early nephroprotective effects in the NO-deficient model of hypertension. These effects could be mediated by amelioration of VEGF expression and reduction of RhoA activity.