Katsuyoshi Seki

Increased Serum Ca 125 Levels During the First Trimester of Pregnancy

An immunoradiometric assay for an ovarian tumor associated antigen (CA 125) has recently been developed. the CA 125 assay was reported to be fairly sensitive for ovarian cancer. However, elevated CA 125 levels were reportedly observed in 1% of healthy controls, 6% of patients with miscellaneous diseases and 29% of patients with non‐gynecological cancer. Therefore, the specificity of the CA 125 assay must be evaluated before its wide clinical application. Furthermore, data on the CA 125 levels in pregnant women have not heretofore been reported. in the present study, CA 125 levels were determined in sera randomly obtained from normal, pregnant women at various weeks of pregnancy and in sera serially collected from women who achieved pregnancy after ovulation induction. When compared with the normal, non‐pregnant state, CA 125 levels in pregnant women were significantly higher during the first trimester, but not during the second and third trimesters. Although CA 125 levels in women during the first trimester of pregnancy were significantly lower than those in patients with ovarian cancer, there was a considerable overlap between them. CA 125 levels were undetectable before pregnancy in all of the 8 patients who achieved pregnancy after ovulation induction. They rose during the first trimester of pregnancy in 7 of the 8 patients, and they decreased thereafter to undetectable levels by the end of the first trimester. the increased CA 125 level in the early pregnancy provides an important information for the clinical application of the CA 125 assay. Pregnancy should be ruled out when increased CA 125 levels are found in women during the childbearing years.

Leiomyosarcoma of the Uterus: Ultrasonography and Serum Lactate Dehydrogenase Level

Between January 1, 1979, and September 30, 1990, a total of 1,886 patients in the National Defense Medical College Hospital, a self-referred population, had a hysterectomy because of signs and symptoms presumably resulting from uterine myomas. After hysterectomy with presumed benign disease, a histologic diagnosis of leiomyosarcoma was made in 7 patients (0.37%). Preoperative diagnosis of leiomyosarcoma was not made in any of the 7 patients. However, serum lactate dehydrogenase levels were abnormally elevated in 3 of them, and degenerative changes were found within the tumor by ultrasonography in 5 of them. Furthermore, increased lactate dehydrogenase levels and degenerative changes within the tumor were found in 3 of the patients whose tumors had 10 or more mitoses per 10 high-power fields. The prognosis for the leiomyosarcomas with increased mitotic rates is very poor. Therefore, a degenerative change within the uterine mass and an increased lactate dehydrogenase level, when present, should suggest the diagnosis of leiomyosarcoma.

Parathyroid Hormone-Related Protein during Pregnancy and the Perinatal Period

To evaluate whether parathyroid hormone-related protein (PTHrP) plays any role in calcium metabolism during pregnancy and the perinatal period, we measured parathyroid hormone (PTH), immunoreactive PTHrP and calcium in maternal serum of women during pregnancy and puerperium, and in maternal and cord serum at delivery. Serum PTH levels in pregnant women were lower than those in nonpregnant women (p < 0.01). However, serum PTHrP levels were similar in the two groups of women. Cord serum total and ionic calcium levels were higher, and cord serum PTH levels were lower compared to maternal values (p < 0.01). Cord serum PTHrP levels were higher than maternal values, and umbilical arterial levels were higher than umbilical venous levels (p < 0.01). Higher levels of PTHrP in umbilical arterial blood than in umbilical venous blood suggest that the main source of cord blood PTHrP may be the fetus. PTHrP is reported to stimulate placental calcium transfer from mother to fetus in animals. The elevated cord blood PTHrP level in association with the decreased PTH level suggests that stimulation of placental calcium transfer by PTHrP may also be operative in humans.

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.

Levels of Glucose and Insulin during Twenty-Four Hours in Hyperprolactinemic Women with Pituitary Microadenoma

Excursions of plasma glucose and insulin throughout the 24-hour metabolic clock were evaluated in hyperprolactinemic women with pituitary microadenoma. The glucose response to food intake and 24-hour excursion of plasma glucose were not altered in hyperprolactinemic women compared to normal women. Premeal and 24-hour insulin levels were significantly increased in hyperprolactinemic women, though fasting insulin levels were not. Postprandial insulin increments appeared to be more sustained in these patients compared to normal women, though the difference was not statistically significant. And therefore the increased 24-hour concentration of insulin in hyperprolactinemic women appears to be due to the sustained insulin response to meals and increased premeal insulin levels. A slight resistance to insulin was observed in hyperprolactinemic women. That the 24-hour excursion of plasma glucose is not altered in hyperprolactinemic women in the face of decreased sensitivity to insulin may be accounted for by the increased insulin secretion.

Serum relaxin and steroid hormones in spontaneous abortions

To assess the capacity of the corpus luteum to secrete steroid hormones and relaxin during spontaneous abortion, human chorionic gonadotropin (hCG), progesterone, 17α‐hydroxyprogesterone (17‐OHP) and relaxin concentrations were determined in serum samples obtained from 16 spontaneously aborting first‐trimester patients and 5 asymptomatic, apparently normal women who subsequently aborted. hCG and P were subnormal in more than half of aborting patients, and 17‐OHP in half of them. However, relaxin was normal in most of them. No patient with subnormal relaxin levels had hCG values in the normal range. Such a relationship was not found between hCG and 17‐OHP values. Hence, decreases in placental activity seem to precede a decrease in luteal ability to secrete relaxin but not to secrete stereoid hormones. Some aborting patients with subnormal 17‐OHP levels had normal relaxin values. All but 1 woman who aborted subsequently had subnormal 17‐OHP values at a time when relaxin levels were normal. Therefore, in some aborting patients, the ability of the corpus luteum to secrete steroid hormones is impaired at a time when its capacity to secrete relaxin is preserved.

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.

Measurement of urinary free β-human chorionic gonadotropin by immunoradiometric assay

An immunoradiometric assay for free beta-human chorionic gonadotropin (F beta hCG) is now available. Measurement of serum F beta hCG has been shown to be valuable for the diagnosis of trophoblastic disease and for screening Downs syndrome pregnancies. Urine specimens may be preferable to blood samples since collection of urine specimens usually are less inconvenient to patients than venipuncture. We have evaluated whether the immunoradiometric assay can be applicable to urine samples. The assay was sensitive and precise. When urine samples were diluted 4-fold or more, the diluted samples gave quantitative values, and recovery of beta hCG added to urine samples was satisfactory. Creatinine corrected urinary F beta hCG levels correlated with serum F beta hCG levels. Thus, the immunoradiometric assay was considered to be applicable to urine samples. Serum F beta hCG to hCG ratio has been reported to be important to distinguish among normal pregnancies, hydatidiform mole and choriocarcinoma. However, urinary F beta hCG to hCG ratio did not significantly correlate with serum F beta hCG to hCG ratio. And therefore, the clinical value of urinary F beta hCG to hCG ratio should be further investigated.

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.

Variability of Cortisol and Adrenocorticotropic Hormone Responses to Metoclopramide during the Menstrual Cycle

Responses of cortisol and adrenocorticotropic hormone (ACTH) to metoclopramide (MCP) were examined in normal women throughout the menstrual cycle. The administration of MCP increased circulating levels of cortisol and ACTH in normal women during the mid-luteal but not during the early and late follicular phases. MCP may stimulate ACTH release through an antidopaminergic mechanism, and endogenous dopaminergic tone is likely to be increased during the luteal phase compared to the follicular phase. Consequently, the positive responses of cortisol and ACTH to MCP observed in the subjects during the mid-luteal phase may be related to the increased dopaminergic tone.