beta-HCG/LH receptor (beta-HCG/LH-R) expression in eutopic endometrium and endometriotic implants: evidence for beta-HCG sensitivity of endometriosis.

BACKGROUND: Luteinizing hormone (LH) and human chorionic gonadotropin (HCG) target their receptor in gonadal and nongonadal cells to stimulate steroidogenesis and cell growth. The aim of the present study was to investigate the expression of HCG/LH-R in endometriosis to elucidate a possible impact of LH and HCG on this disease. MATERIALS AND METHODS: Analysis of HCG/LH-R protein expression in 23 paired samples of ectopic and eutopic tissue of cycling women with endometriosis and in endometrial samples from 22 healthy controls was conducted via immunofluorescence. HCG and HCG/LH-R gene expression in endometriotic lesions was confirmed by reverse-transcriptase polymerase chain reaction. RESULTS: In endometriotic implants, epithelial HCG/LH-R was found in 12/23 samples. No significant differences in HCG/LH-R levels were observed when compared with glands of uterine endometrium from the same patients or healthy controls. Messenger RNA transcripts for HCG were detected in all 12 samples, whereas HCG/LH-R mRNAs were observed in 10 of the 12 endometriotic lesions investigated. CONCLUSIONS: Although HCG/LH-R was not found to be selectively upregulated in endometriosis, the mere presence of HCG/LH-R in endometriotic tissue may suggest sensitivity of endometriosis to HCG and LH that target HCG/LH-R.

Plasminogen activator inhibitor 1 gene polymorphism and gestational diabetes mellitus.

OBJECTIVE: Plasminogen activator inhibitor 1 is thought to play a role in the pathogenesis of obesity and insulin resistance. Therefore, we examined a single nucleotide exchange in this gene in women with gestational diabetes mellitus. METHODS: A total of 887 unselected women were prospectively screened for gestational diabetes mellitus by oral glucose testing between the 24th and 28th weeks of gestation. Eighty white women of this collective, 40 patients with a pathological oral glucose tolerance test and 40 normal control subjects, were randomly selected. DNA samples were isolated from the sera and analyzed for the functional -675 4G/5G promotor polymorphisms of the plasminogen activator inhibitor 1 gene. RESULTS: Women with gestational diabetes mellitus were significantly older and had a significantly higher body mass index (BMI) than those who did not have gestational diabetes mellitus. Women with normal glucose tolerance were significantly more often homozygous for the 5G allele (P = .01), independently of maternal age or BMI. Low fasting glucose values in the oral glucose tolerance test were significantly related to homozygosity for 5G (P = .02). CONCLUSION: Homozygosity for the 5G allele of the plasminogen activator inhibitor 1 gene is associated with normal glucose tolerance in pregnant women. These findings further support a possible role of plasminogen activator inhibitor in the development of gestational diabetes mellitus. LEVEL OF EVIDENCE: II-2.

Peroxisome proliferator-activated receptor gamma coactivator-1alpha gene variations are not associated with gestational diabetes mellitus.

OBJECTIVE: Epidemiologic, pathophysiologic, and genetic data suggest a close link between gestational diabetes mellitus (GDM) and type 2 diabetes. Previous studies yielded controversial results on the impact of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1) gene variations on the development of type 2 diabetes mellitus. Therefore, we examined two common single nucleotide polymorphisms (SNP) of this gene in women with GDM. METHODS: We assessed a total of 875 women by oral glucose tolerance testing (OGTT). Two hundred women of this population, 100 patients with an abnormal OGTT and 100 normal controls, were randomly selected. DNA samples isolated from the blood of the control and study groups were analyzed with respect to the SNP Gly482Ser and Thr394Thr of the PGC-1 gene using polymerase chain reaction (PCR) amplification and restriction analysis. Furthermore, a potential interaction between the Gly482Ser and the Thr394Thr variant on the risk of GDM was investigated. RESULTS: Women with GDM were significantly older (32.2 +/-5.5 years vs 29.7 +/- 6.1 years; P = .005), had higher body mass indices (BMI; 28.0 +/- 7.1 kg/m2 vs 25.0 +/- 5.7 kg/m2; P = .002) and displayed higher hemoglobin A1c (HbA1c) values (5.6 +/- 0.9 vs 4.9 +/- 0.5; P <.001). There was no significant difference between the allele distribution of the two polymorphisms in women with and without GDM. No significant associations between the two polymorphisms and BMI or OGTT values were observed. When the different haplotype combinations of the two loci were analyzed for the risk of GDM, no significant association could be found. CONCLUSION: Based on our data, the Gly482Ser and the Thr394Thr polymorphisms of the PGC-1 gene are not associated with the development of GDM.