Increased lipid peroxidation in adult GH-deficient patients: effects of short-term GH administration.

OBJECTIVE: Adult GH deficiency (GHD) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality. Oxidative stress appears to play an important role in early atherogenesis. Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium. Its concentrations are increased in GHD, but the association between this abnormality and oxidative stress is still unclear, due to the discordant results yielded by the few available studies. DESIGN AND METHODS: In 13 GHD patients, plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH (rhGH) and compared with those of 13 age- and sex-matched controls. In the same subjects, the so-called "lag-time", an index of anti-oxidant activity and thus of plasma oxidative balance, was also measured using a fluorescence kinetics method. RESULTS: Before treatment, peroxide levels were significantly higher in patients than in controls (374.0+/-31.52 vs 268.0+/-8.51 U.C., p<0.01), whereas the lag-time was significantly lower (113.0+/-10.70 vs 168.0+/-7.80 min, p<0.01). RhGH administration to patients resulted both in a significant decrease in lipid peroxide levels (from 374.0+/-31.52 to 336.0+/-33.17 U.C., p<0.01) and a significant prolongation of lag-time (from 113.0+/-10.70 to 144.0+/-15.00 min, p<0.01). After treatment, both parameters were no longer significantly different in patients and controls. Lag-time and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients. After replacement therapy, however, lag-time was positively (r2= 0.62, p<0.01), and peroxide levels negatively (r2=0.41, p<0.05), correlated with IGF-I levels. CONCLUSIONS: These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former. This abnormality, likely contributing to the increased atherogenic risk of GHD patients, is corrected by short-term GH administration at a dose able to increase, although not to fully normalize, IGF-I levels.

Tissue- and site-specific gene expression of type 2 17beta-hydroxysteroid dehydrogenase: in situ hybridization and specificenzymatic activity studies in human placental endothelial cells of the arterial system.

Progesterone and estradiol are the most potent human sex steroid hormones of placental origin and are essential to the maintenance of pregnancy, the timing of parturition, the maturation of many fetal organs, and the preparation of the maternal reproductive system. Naturally, regulatory mechanisms must be in place to coordinate the synthesis and inactivation of these two hormones. We have previously shown that the highest levels of type 1 and type 2 17beta-hydroxysteroid dehydrogenase (17betaHSD) messenger ribonucleic acids (mRNAs) occur in the placenta, particularly in the villi. However, in contrast to type 1 17betaHSD mRNA, type 2 17betaHSD mRNA was not detectable in cell cultures of human cytotrophoblasts or syncytiotrophoblasts. Using in situ hybridization, we unequivocally identified endothelial cells as the only cell type expressing the type 2 17betaHSD gene in fetal villi. Moreover, type 2 17betaHSD mRNA was specifically detected in the endothelial cells of the arterial system, and at higher levels in the villi compared with endothelial cells of the cord arteries when the two tissue sections were cohybridized. In fact, both mRNA levels and enzymatic activity are at their highest levels in arterial endothelial cells. In conclusion, the endothelial cells of the villous arterioles are the primary site of type 2 17betaHSD gene expression. This suggests a regulatory role for these cells in the control of progestin, androgen, and estrogen levels during pregnancy, thus opening a whole new way of viewing regionalization and localization of steroidogenesis in the human villi.

Parental factors influencing patterns of prenatal care utilization.

OBJECTIVES: The objectives of this study are to examine the influence of paternal and maternal education and marital status on the initiation and adequate use of prenatal care services. METHODS: Data were obtained from the 1990-1991 Minnesota Live Birth file. Single live births to white resident mothers who were 21 years of age or older were selected for investigation. After these selections 102,798 cases were analyzed. RESULTS: Logistic regression was used to examine the association of parental characteristics on the following three measures of poor prenatal care use: (1) receiving no prenatal care; (2) initiating care later than the first trimester; and (3) given a first trimester start of care, receiving less than the recommended number of prenatal care visits. Within each maternal education stratum, an increased risk of delayed initiation and less efficient use of prenatal care were observed for lower paternal educational attainment. Unmarried women, regardless of educational level, exhibited more than a tenfold risk of receiving no prenatal care, and unmarried women of low educational attainment exhibited the highest risk of delayed care. CONCLUSIONS: A persistent positive effect of increasing paternal education on the level of adequacy of prenatal care utilization within all maternal marital status and educational attainment groups poses further challenges to our understanding of the factors that influence prenatal care use.

Gestational development of human placental 17 beta-hydroxysteroid oxidoreductase types 1 and 2.

Human placenta is a rich source of 17 beta-hydroxysteroid oxidoreductase (17-HOR) type 1, a cytosolic enzyme highly specific for 17 beta-oestradiol, and type 2, a microsomal form reactive with both oestradiol and testosterone. Although a number of studies have established that 17-HOR activity is present in placenta as early as weeks 4-5 of gestation, more specific data on the pattern of development of these two enzyme forms are lacking. In this study, samples of villous tissue from weeks 7-20 of gestation were fractionated into cytosol and microsomes and 17-HOR activity assayed under conditions which differentiate between the two enzyme types. Type 1 activity with oestradiol of cytosol and microsomal type 2 activity with oestradiol and testosterone increased from week 7 to week 20. Activities at 17-20 weeks approximated those at 38-40 weeks. The high, cytosolic oestradiol/T activity ratio (160 +/- 20), characteristic of 17-HOR type 1, was constant between weeks 7 and 20, as was the low microsomal ratio (3.4 +/- 0.4) characteristic of the type 2 activity. There was a relationship between cytosolic type 1 activity and microsomal type 2 activity between weeks 7 and 20 (r = 0.59, P = 0.0055). These results indicate both activities increase coincident with the luteal-placental shift and that their temporal patterns of development are related between weeks 7 and 20 of gestation.

Prenatal care utilization in Minnesota. Patterns of concern, areas for improvement.

We conducted an analysis of prenatal care utilization among Minnesota resident mothers for the years 1990 to 1991 to determine why this state ranks poorly in prenatal care use while its infant mortality rate is one of the lowest in the nation. We found that 6% of women began care in the first trimester yet did not receive an adequate number of visits. These women were more likely to deliver preterm, low birthweight infants than women who started care later. Fifteen percent of women had records missing important data, and these women also had higher rates of poor pregnancy outcomes. Our findings have implications for maternal outreach and follow-up efforts and suggest potential benefits from private and public health collaborations. In addition, efforts to improve the quality of data reporting should begin immediately.