Noriko Makimura

Calcium-regulating hormones and osteocalcin levels during pregnancy: A longitudinal study

We measured serum concentrations of calcium-regulating hormones and osteocalcin in 20 women longitudinally throughout pregnancy, 1,25-Dihydroxyvitamin D levels were high early in pregnancy and increased with advancing gestation. Parathyroid hormone and osteocalcin levels were low in early pregnancy. They declined toward the middle of pregnancy, but increased in late pregnancy. The serum osteocalcin level correlated with the parathyroid hormone level. The synthesis of osteocalcin by osteoblasts is stimulated by the action of 1,25-dihydroxyvitamin D, and serum osteocalcin levels are also related to the levels of parathyroid hormone. During early and mid pregnancy, the stimulatory effect of 1,25-dihydroxyvitamin D on the synthesis of osteocalcin may be overridden by the inhibitory effect of declining parathyroid hormone levels. The increase in osteocalcin level in late pregnancy may be a consequence of increasing levels of both parathyroid hormone and 1,25-dihydroxyvitamin D.

Cord blood levels of calcium-regulating hormones and osteocalcin in premature infants.

We measured cord blood levels of calcium-regulating hormones and osteocalcin in 34 premature infants of various gestational ages. 1,25(OH)2D levels were low in mid-gestation and increased with advancing gestation. Parathyroid hormone levels were low, and calcitonin levels were high in mid-gestation. Both of them declined with advancing gestation. Osteocalcin levels were high in mid-gestation. They increased from 22 weeks through 27 weeks of gestational age, and decreased thereafter. Circulating osteocalcin is considered as a clinical marker of bone turnover. However, cord blood osteocalcin decreased between 27 and 36 weeks of gestation during which period calcium accumulation by the fetus increases. Therefore, cord blood osteocalcin does not appear to reflect fetal bone formation.

Parathyroid-hormone-related protein in human milk and its relation to milk calcium

Parathyroid-hormone-related protein (PTHrP) is found in high concentrations in human milk. One of the possible physiological roles of PTHrP may be the regulation of calcium transport through the mammary gland. The relationship between milk PTHrP and Ca concentrations was evaluated in lactating women in the present study. Milk PTHrP has been quantified by immunoradiometric assay (IRMA) and radioimmunoassay (RIA). The IRMA detects PTHrP 1-72, and the RIA carboxyterminal region of PTHrP (C-PTHrP). Milk PTHrP 1-72 and C-PTHrP concentrations did not significantly change by breast-feeding. Milk PTHrP 1-72 changed significantly by the time of day, in contrast to C-PTHrP. Thus, PTHrP 1-72 rather than C-PTHrP may reflect an acute change in mammary PTHrP secretion. In lactating women in whom milk PTHrP and calcium concentrations were serially measured at 5-day intervals up to 26-30 days after delivery, milk PTHrP 1-72 progressively increased with duration of lactation. In contrast to PTHrP 1-72, milk C-PTHrP decreased during this period. And milk PTHrP 1-72 levels inversely correlated with C-PTHrP levels. Milk C-PTHrP but not PTHrP 1-72 levels correlated significantly with milk Ca concentrations. Although it is not certain whether the correlation between milk C-PTHrP and Ca levels is causally related, it may be that fragments of PTHrP detected as C-PTHrP are involved in the regulation of Ca transport through the mammary gland in women.

Gene Expressions of Oxytocin and Oxytocin Receptor in Cumulus Cells of Human Ovary

Oxytocin (OT) has been detected in mammalian granulosa-luteal cells during the early stages. The purpose of this study was to explore gene expressions of OT and OT receptor (OTR) in human cumulus cells. Cumulus cells enclosing a mature oocyte were obtained from 6 women undergoing clinical in vitro fertilization and embryo transfer programs. OT and OTR gene expressions were investigated by employing reverse transcription polymerase chain reaction and reverse transcription polymerase chain reaction/single-strand conformation polymorphism methods. OT gene expression in the cumulus cells was positive in 5 women and weakly positive in the remaining patient. The structure of OT mRNA in the cumulus cells was equivalent to that in human hypothalamus. OTR gene expression was also observed in the cumulus cells. This study is the first to describe the simultaneous expression of both OT and OTR genes in human cumulus cells. It is suggested that local OT plays some important roles in fertility through modification of the micro-environment around the oocyte.

Immunological and endocrinological studies on lymphocyte subpopulation and medical treatment for infertility in patients with endometriosis

We investigated the relationship between interleukin-6 (IL-6) levels and subset profiles of T lymphocyte (T-cell) and macrophage in peritoneal fluid (PF) with or without endometriosis (EM). IL-6 levels in PF with EM were significantly higher than those without EM. IL-6 producing cells with EM were analyzed in each activated mature T-cell (CD3+CD69+) and macrophage (CD14+) were 0.5 and 3.5%, respectively, whereas it was mostly negative in those without EM. Cytotoxic T-cell (CD8+CD11b-) profiles in PF with EM were also quiet different from those without EM. Cellular immunity in the peripheral blood did not change during the course of IVF-ET cycles, although plasma levels of ovarian steroid hormones significantly increased comparing with that in normal ovarian cycles. Cytotoxic T-cell type 1 (Tc1) profiles might be useful predictive values in the pregnancy outcome for infertile patients with EM.

Comparison of plasma oxytocin levels during spontaneous labor and labor induced by amniotomy, prostaglandin F2α, and prostaglandin E2

Plasma concentrations of oxytocin in nine spontaneous labors (group 1), nine amniotomy-induced labors (group 2), six prostaglandin F2 alpha-induced labors (group 3), and five prostaglandin E2-induced labors (group 4) were determined at the stages of 1 to 7 days preceding the onset of labor, onset of labor, and established labor, by means of unextracted radioimmunoassay. The levels of oxytocin in the stage preceding the onset of labor in group 1 were not significantly different from the levels of oxytocin in the corresponding stages in groups 2, 3, and 4. However, the levels of oxytocin in the stages of onset of labor and established labor in group 1 were significantly higher than those in the corresponding stages in groups 2, 3, and 4. These results suggest that oxytocin plays a leading role in the onset and progress of spontaneous labor, whereas something other than oxytocin might be involved in the labor induced by amniotomy alone or by prostaglandins.

A Novel Biological Aspect of Ovarian Oxytocin: Oxytocin Gene Expression in Cumulus/Luteal Cells and the Effect of Oxytocin on Embryogenesis in Fertilized Oocytes

Recently, several reports have demonstrated the presence of oxytocin (OT) in the corpus luteum of mammalian species. However, the biological role of ovarian OT remains obscure. This study was performed to examine OT gene expression in cumulus cells of mice and humans, and in human corpus luteum, and the role of OT in early embryogenesis. OT gene and OT mRNA were analyzed by reverse transcription-polymerase chain reaction, with single-strand-conformation polymorphism and heteroduplex procedures. OT-treated in-vitro-fertilized mouse oocytes were cultured and the rate of blastocyst development estimated. An immunohistochemical study was also carried out to detect OT on the surface of the mouse oocytes.

Comparison of low-dose dienogest with low-dose danazol for long-term treatment of adenomyosis.

INTRODUCTION: The objective of this study was to compare low-dose dienogest with low-dose danazol for the long-term treatment of adenomyosis because evidence regarding the effects of its long-term use is scarce. METHODS: We compared 20 patients receiving low-dose dienogest treatment with 22 patients receiving low-dose danazol treatment for endometriosis including adenomyosis. We evaluated the effects and complications of low-dose dienogest treatment in comparison with those of low-dose danazol treatment. In addition, the values of serum hormones, tumor markers, and lipid metabolism were compared between both groups. This study was approved by the institutional review board. RESULT: The daily dose of dienogest could be decreased from 2.0 to 1.5 or 1.0 mg. Although irregular genital bleeding was recorded as an adverse effect, it was controllable; however, the monthly cost incurred by the low-dose dienogest treatment group was higher than that by the low-dose danazol treatment group. The daily dose of danazol could be decreased from 200 to 50 or 33 mg in patients with adenomyosis, but it was difficult to determine the adequate dose for individual patients. Some patients in the low-dose danazol treatment group developed polycythemia as an adverse effect, and the administration of the drug was therefore discontinued. There was no significant difference in the values of serum hormones, tumor markers, or lipid metabolism between both groups. CONCLUSION: We suggest that both low-dose dienogest and low-dose danazol are effective and safe for long-term management of endometriosis. However, the selection of either treatment for adenomyosis depends on each patients baseline condition.

Changes in Plasma Cyclic AMP and Cyclic GMP during Spontaneous Labor and Labor Induced by Oxytocin, Prostaglandin F2α and Prostaglandin E2

To investigate the response of cyclic nucleotides to the oxytocic agents administered for induction of labor, plasma concentrations of cyclic AMP (cAMP) and cyclic GMP (cGMP) were determined by radioimmunoassay during spontaneous labor and labor induced by oxytocin (OT), prostaglandin F2 alpha (PGF2 alpha), or PGE2 (PGE2). Subjects were 7 Japanese women in each labor group. Plasma cAMP levels significantly rose at the time of crowning of the fetal head in all 4 groups. They did not increase until that time in the 3 labor groups (spontaneous, OT-induced, and PGF2 alpha-induced labor groups). In the PGE2-induced labor group, plasma cAMP levels were significantly higher at labor onset (mean +/- SEM = 16.5 +/- 1.3 pg/ml) when compared to the pretreatment values (13.7 +/- 1.0 pg/ml), and increased thereafter gradually toward the time of crowning of the head (26.3 +/- 2.0 pg/ml). Plasma cGMP levels in the OT-induced group significantly rose after the onset of labor and remained at a high level until expulsion of the fetus. Plasma cGMP levels in the other groups did not change significantly throughout labor. These results suggest that cAMP may be involved in the labor process induced by PGE2, and that cGMP may be in that induced by OT.

Influence of light irradiation an the development of mouse eggs in culture

We tnvestlgated the Influence of l lght envlronment on the development of mouse egg in virro. The 1-cell mouse eggs were irradlated by varlous laser l ights of whlch wavelengths were 632.8nm, 543nm, and 442nm in vitro. Actual llght environment by means of the microscope IIght source In IVFET ( in vitro fertlllzatlon-embryo transfer) was measured to set the I lght dose In th is experlment. Mouse eggs were cultured to observe cellular development stage. In case of 632.8nm radiation of 500kJ/m2 I n dose ( 2 0 t lmes larger than actual l lght envlronment), 97% of eggs stopped their division. In the case of 543nm and 442nm radiations no influences were observed In egg division. These results suggested that l lght environment migh t af fect o n the development of mouse egg in vitro.