Katherine H. Moore

Comparison of the lipoprotein, carbohydrate, and hemostatic effects of phasic oral contraceptives containing desogestrel or levonorgestrel

Desogestrel (DSG) is a less-androgenic progestogen than levonorgestrel (LNG). This difference in androgenicity may be responsible for observed differences in metabolic effects between oral contraceptive (OC) formulations containing almost equivalent estrogen doses but with either DSG or LNG as a progestogen. To test the hypothesis, a prospective 9-month randomized comparison of plasma lipids, glucose, insulin, hemostasis, and sex hormone binding globulin (SHBG) was conducted in 66 healthy women using phasic formulations of OCs containing either DSG (DSG-OC) or LNG (LNG-OC). The study results showed that SHBG increased 3-fold with DSG-OC and 2-fold with LNG-OC. DSG-OC increased HDL-C, HDL(2)-C and HDL(3)-C; LDL-C decreased transiently. LNG-OC decreased HDL(2)-C and increased HDL(3)-C; HDL-C was unchanged and LDL-C decreased transiently. Both formulations increased VLDL-C and triglycerides, more with DSG-OC, but apolipoprotein B levels increased equally. Apo A-I and A-II increased more with DSG-OC than with LNG-OC. Neither formulation altered Lp(a) or fasting glucose and insulin levels. Postprandially, both formulations decreased glucose and increased insulin responses, but to an equivalent degree. Both OCs slightly enhanced procoagulant and profibrinolytic parameters to the same extent except for internally compensating decreases in Factor V and protein S with DSG-OC. In summary, at almost equivalent estrogen doses, a phasic OC containing DSG compared with LNG has a less androgenic effect on lipoproteins and SHBG, similar effects on hemostatic parameters with lower protein S and factor V activity and equivalent effects on carbohydrate metabolism. The lipoprotein, SHBG, and protein S and factor V differences are likely due to the lesser androgenicity of DSG allowing for a greater expression of the dose of estrogen.

Sex hormone binding globulin mRNA in human breast cancer: Detection in cell lines and tumor samples

Sex hormone binding globulin (SHBG) is a high affinity binding protein for estrogens and androgens. SHBG has been found in breast tissue and cell lines through immunostaining. The goal of this series of experiments was to determine whether mRNA for SHBG is expressed in breast cancer cell lines and tumor tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect SHBG and beta-2 microglobulin (control for tissue extractions). Three breast cancer cell lines, ZR-75-1, MCF-7, and MDA-MB-231 and 56 breast tissue samples were collected and analysed for SHBG mRNA expression. mRNA was successfully extracted from 30 of these breast tissue samples. SHBG mRNA was detected in ZR-75-1, MCF-7 and MDA-MB-231 cells, and in 11 of the breast tissue samples. Two PCR products were routinely amplified from the breast cancer cell line RNA, one at approximately 500 bp and another at approximately 300 bp. The DNA sequence of the 300 bp PCR produce was consistent with alternate splicing of the SHBG mRNA, where exon 7 is deleted, and is accompanied by a point deletion at the beginning of exon 8. SHBG protein production from the three breast cancer cell lines was detected by immunoprecipitation using an affinity purified SHBG antibody. SHBG mRNA was found in 11 of 30 samples of breast tissue. Some samples expressed only the 500 bp or the 300 bp PCR product, whereas others expressed both PCR products. The presence of SHBG mRNA in these samples was not associated with either the presence or absence of steroid receptors. SHBG mRNA is thus expressed in breast cancer cell lines, and in some breast tissue samples.

Fetoplacental vascular tone during fetal circuit acidosis and acidosis with hypoxia in the ex vivo perfused human placental cotyledon

OBJECTIVES Our purpose was to determine the effects of acidosis and acidosis-hypoxia on fetoplacental perfusion pressure and its response to angiotensin II. STUDY DESIGN Perfused cotyledons from 14 placentas were studied with either an acidotic fetal circuit perfusate (n = 7) or an acidotic-hypoxic fetal circuit perfusate (n = 7). Each cotyledons fetal vasculature was initially perfused under standard conditions and bolus injected with 1 x 10(-10) moles of angiotensin II. Fetoplacental perfusate was then replaced with either an acidotic medium (pH 6.90 to 7.00 and Po2 516 to 613 mm Hg) or an acidotic-hypoxic medium (pH 6.90 to 7.00 and Po2 20 to 25 mm Hg) followed by an angiotensin II injection. The vasculature was subsequently recovered with standard perfusate and again injected with angiotensin II. Perfusion pressures within each group were compared by one-way analysis of variance, and results were expressed as mean pressure +/- SEM. RESULTS Resting fetoplacental perfusion pressure did not change when the fetal circuit perfusate was made acidotic (28 +/- 1 mm Hg vs 25 +/- 2 mm Hg) or acidotic-hypoxic (26 +/- 2 mm Hg vs 25 +/- 2 mm Hg). The maximal fetoplacental perfusion pressure achieved in response to angiotensin II did not differ with an acidotic perfusate (41 +/- 2 mm Hg vs 38 +/- 1 mm Hg) or with an acidotic-hypoxic perfusate (39 +/- 2 mm Hg vs 36 +/- 2 mm Hg). CONCLUSIONS In the perfused placental cotyledon fetoplacental perfusion pressure and pressor response to angiotensin II are not affected by fetal circuit acidosis or acidosis-hypoxia. This suggests that neither fetal acidosis nor fetal acidosis combined with hypoxia has a direct effect on fetoplacental vascular tone.

Gastrin-releasing peptide: a potential growth factor expressed in human neuroblastoma tumors

Abstract PURPOSE: Gastrin-releasing peptide (GRP) is a 27–amino acid neuropeptide that has been identified in the cytoplasm of many neuroendocrine tumors. Gastrin releasing peptide has been labeled as an autocrine growth factor in small cell lung carcinomas. Recent work has also shown this to be true in the growth of neuroblastoma cells in vitro. The purpose of this study was to demonstrate GRP and its receptor (GRP-R) in resected human neuroblastomas and to correlate the presence or absence with other known predictors of poor prognosis. Methods To demonstrate the presence of GRP and GRP-R mRNA, total RNA was extracted from human neuroblastoma cells. A reverse transcription-polymerase chain reaction (RT-PCR) was then performed using specific primers. The products of the RT-PCR were then confirmed to be GRP and GRP-R cDNA by Southern blot analysis. The RT-PCR products were then sequenced, and these sequences were compared with the know sequences of GRP and GRP-R DNA. Results N = 19. GRP and GRP-R mRNA were present in all neuroblastoma specimens. Although no correlation with other known predictors of poor prognosis existed, transcripts of four different sizes (400, 450, 500, and 950 bp) were seen in the GRP-R transcripts. The sequences of the 950 bp–sized transcript reverse transcription PCR products were identical to the known GRP-R. Conclusions We conclude that gastrin releasing peptide and gastrin releasing peptide receptor mRNA are present in all human neuroblastomas. Although qualitatively it appears to lack prognostic significance, its ubiquitous nature in the tumor suggests it may be a useful target on which to base future treatment modalities.

Adrenomedullin concentrations in umbilical cord plasma of uncomplicated term pregnancies

OBJECTIVE The studys objective was to determine whether there is a difference in the plasma concentration of adrenomedullin, a hypotensive peptide, between arterial and venous umbilical cord blood of uncomplicated gestations with vaginal delivery. STUDY DESIGN Arterial and venous umbilical cord blood was obtained immediately after vaginal delivery of 44 term infants with uncomplicated antepartum and intrapartum courses. Radioimmunoassay was performed to assess adrenomedullin concentrations in the plasma. The paired t test was used to compare arterial and venous concentrations. Significance was set at P < .05. RESULTS Mean +/- SE adrenomedullin concentrations were 178.7 +/- 4.7 pg/mL and 190.6 +/- 6.3 pg/mL for arterial and venous cord plasma, respectively. The difference between the 2 concentrations was not significant (11.8 pg/mL, P = .09). CONCLUSION Arterial and venous umbilical plasma concentrations of adrenomedullin do not differ significantly in uncomplicated gestations terminating with uncomplicated vaginal deliveries. This suggests that in the normal state there is neither net production nor net clearance of adrenomedullin in the placenta.