Satoshi Nakago

Effects of progesterone on growth factor expression in human uterine leiomyoma

It is now evident that the use of levonorgestrel-releasing intrauterine system (LNg-IUS) is effective for long-term management of menorrhagic women with uterine myomas because of a striking reduction in menorrhagia. This prompted us to characterize the effects of progesterone (P4) on the growth and apoptosis of uterine leiomyoma cells. On the other hand, we have recently noted that epidermal growth factor (EGF) and IGF-I play a crucial role in prompting uterine leiomyoma growth through stimulating the proliferative potential and inhibiting apoptosis of cultured human leiomyoma cells. In the present review, attention was paid to evaluate the effects of P4 on the expression of growth factors (EGF, IGF-I) and apoptosis-related factors (TNFalpha, Bcl-2 protein) in cultured uterine leiomyoma cells. Treatment with P4 augmented EGF and Bcl-2 protein expression, but inhibited IGF-I and TNFalpha expression in cultured leiomyoma cells. It is known that TNFalpha induces apoptosis in a variety of cell types and Bcl-2 protein is an apoptosis-inhibiting gene product. Thus, the results obtained suggest that P4 has dual actions on uterine leiomyoma growth: one is to stimulate leiomyoma cell growth and survival through up-regulating EGF and Bcl-2 protein expression as well as down-regulating TNFalpha expression in those cells, and the other is to inhibit leiomyoma cell growth through down-regulating IGF-I expression in those cells. This may explain why the size of uterine myomas during use of LNg-IUS increases in some but decreases in other instances. This may also explain why the size of uterine myomas during pregnancy does not increase despite the overwhelming increase in circulating concentrations of sex steroid hormones.

Dysfibrinogenemia during pregnancy treated successfully with fibrinogen

There are three types of congenital abnormalities associated with fibrinogen: afibrinogenemia, hypofibrinogenemia and dysfibrinogenemia. Of these, dysfibrinogenemia is usually clinically silent or is associated with mild to moderate bleeding tendency or defective wound healing. The obstetric complications of dysfibrinogenemia include first-trimester abortion, hemorrhage and placental abruption during pregnancy, and thrombophlebitis (1). We report a case of a dysfibrinogenemic patient with a history of recurrent fetal loss due to placental abruption, which was successfully treated with fibrinogen prophylaxis.

Effects of Combined Estriol/Pravastatin Therapy on Intima-Media Thickness of Common Carotid Artery in Hyperlipidemic Postmenopausal Women

Background: Several studies show that 17β-estradiol (E2) has protective effects on atherosclerosis in the arterial wall in postmenopausal women. Little information is, however, available regarding the effect of estriol (E3) on atherosclerosis. This study was conducted to investigate the effects of E3 alone and combined E3/pravastatin therapy on intima-media thickness (IMT) of common carotid artery in postmenopausal women. Methods: Thirty-three postmenopausal women were allocated to four groups: daily treatment with E3 (2 mg) alone (E3 group, n = 10), pravastatin (10 mg) alone (pravastatin group, n = 6), combined treatment with E3 (2 mg) and pravastatin (10 mg; E3/pravastatin group, n = 7) and untreated control group (n = 10). All women attended the Kobe University Hospital once a year for routine gynecological and ultrasonographic examinations for the evaluation of atherosclerosis. Results: A significant decrease in IMT was noted in the E3/pravastatin group compared with that in the untreated control group (p < 0.05), whereas there was no significant difference in the reduction rate of IMT in the pravastatin group, E3 group and untreated control group. Conclusions: The combined E3/pravastatin therapy appeared to retard the progression of atherosclerosis in postmenopausal women.

Effects of estriol on cell viability and 1,25-dihydroxyvitamin D3 receptor mRNA expression in cultured human osteoblast-like cells.

It is clinically evident that administration of estriol (E3) increases the bone mass density of the lumbar vertebrae in postmenopausal women, and that combined treatment with estrogen and 1,25-dihydroxyvitamin D3(VD3) increases femoral neck bone mass density compared with treatment with estrogen alone in postmenopausal osteoporotic women. However, the molecular mechanism whereby treatment with E3affects osteoblast cell function is still unknown. This study was conducted first to examine the comparative effects of E3and VD3on the cell viability of cultured human osteoblast-like cells (HOS) and second to determine whether E3affects VD3receptor mRNA expression in HOS. The cell viability and VD3receptor mRNA expression of cultured HOS were assessed by MTT assay and semiquantitative reverse transcriptase—polymerase chain reaction with Southern blot analysis, respectively. The treatment with E3increased the cell viability of cultured HOS compared with untreated control cultures. The increase in cell viability caused by the treatment with E3was further augmented by the combined treatment with VD3. The addition of either E3(3.52u2009×u200910−8u200amol/l) or E3(3.52u2009×u200910−7u200amol/l) to cultured HOS for 24u200ah resulted in a fourfold and eightfold increase, respectively, in VD3receptor mRNA expression in HOS, compared with that in untreated control cultures. These results suggest that E3may up-regulate the cell viability of osteoblast cells, and that the concomitant treatment with E3and VD3further augments the cell viability being associated with an E3-induced increase in VD3receptor mRNA expression in those cells.

栄養代謝状態とラット母獣血中Insulin-like Growth Factor-1 (IGF-1) の動態に関する基礎的検討

The effects of nutrition on serum insulin-like growth factor-1 (IGF-1) concentrations during pregnancy of rats were investigated by using rat cultured hepatocytes in vitro, and by the assessment of nitrogen balance in vivo. IGF-1 concentration was measured by radioimmunoassay, and nitrogen balance was calculated by Pregl-Dumas method. The results were as follows: (1) Cultured rat hepatocytes produced IGF-1 in medium and it was significantly stimulated by the addition of various concentrations of glucose (1.1-4.4 mM) and/or several amino acid concentrations in a dose-related manner. (2) Serum IGF-1 concentrations, which indicated 368.6 +/- 143.8 ng/ml in a non-pregnant fed state, markedly decreased in a fasted state, reaching the levels of 143.8 +/- 30.4 ng/ml after 72 hours fasting. Nitrogen balance in these fasted rats also decreased according to the fasted period. (3) In early pregnancy (Day 0-12), serum IGF-1 concentrations were indistinguishable from those of non-pregnant fed rats. It gradually declined after the 13th day of pregnancy and reached the minimum levels of 77.0 +/- 12.1 ng/ml on the 21st day. On the other hand, mean nitrogen balance which was calculated from the difference of nitrogen retention in the maternal body and that in the fetal body, also decreased after 13 days of pregnancy and reached the levels of 14.9 g/day on the 21st day of pregnancy. These results suggested that IGF-1 concentrations in rat serum and conditioned medium might be regulated by nutritional factors, i.e., glucose and/or several amino acids. The curious profiles of IGF-1 concentrations observed in pregnant rats might be due in part to the effects of nutritional changes between the maternal and fetal body, especially, the changes of protein metabolism represented by the nitrogen balance.