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Biomedical subjects

S Tojo

Publications and source records attributed to S Tojo.

At least 109 records · Page 6Linked to original sources
PubMed1982

[Studies on the secretion of human placental lactogen from human trophoblastic tissues (author's transl)].

In order to study the secretory mechanism of human placental lactogen (hPL:hCS) from trophoblastic tissues, tissue culture and new placental perifusion systems were developed and used to clarify the effect of various substances on the secretion of hPL. These substances were (1), metal ions([Ca2+], [K+], [mg2+], [Na+]); (2) growth hormone and prolactin releasing or inhibiting factors (arginine, TRH, somatostatin, dopamine); (3) LH-RH, dibutyryl cyclic-AMP which stimulates hCG secretion; (4) prostaglandins F2 alpha and E2, bradykinin; (5) EGF and insulin which have the receptors in the placenta; (6) glucose. It was found that most of the substances examined had no effect on the secretion of hPL, except dopamine and glucose. The effect of dopamine in the tissue culture system is dose-dependent. At high concentrations dopamine slightly inhibited hPL secretion(5mM: 38.6 +/- 15.0 and 10mM; 35.7 +/- 19.0 micrograms/g wet tissue) compared with the control (63.2 +/- 29.8 microgram/g wet tissue). However, these effects may be due to the deviation of pH in the medium from the direct addition of dopamine hydrochloride. At a low concentration(1mM) it was observed to have a rather stimulatory effect (125.7 +/- 18.0 micrograms/g wet tissue, p less than 0.05), but in the perifusion system, this effect could not be observed. The addition of glucose in the perifusion system gave a slightly higher hPL secretion than that of the control. Perhaps this resulted from increased cell activity rather than a stimulatory effect. an incorporation experiment of [3H] leucine was also carried out to study the biosynthesis of hPL. Newly synthesized ([3H]-labelled) hPL was secreted into the medium within two hours. Furthermore, a labelled larger molecular weight substance together with the tritiated hPL was also observed on a Sephadex G-100 gel chromatography. These labelled substances were immunoprecipitable using an anti-hPL serum, indicating that the substances contain the same immunological determinants. This result indicates that the larger molecular substance may represent the biosynthetic precursor or the aggregate of hPL. These data indicate that the secretion of hPL has a unique mechanism, different from GH and PRL, and may be self regulated.

Arginine↗
PubMed1982

[The response of free alpha-subunit of glycoprotein hormones to LH-RH administration (author's transl)].

The responses of immunoreactive free alpha-subunit of glycoprotein hormones to LH-RH administration were studied in normal men and women, and in patients with hypergonadotropic hypogonadism, hypogonadotropic hypogonadism, trophoblastic disease and isolated ectopic alpha-subunit producing tumor. In patients with hypergonadotropic hypergonadism, basal levels of serum alpha-subunit were elevated and the responses to LH-RH were also excessive compared to those of normal men and women. Conversely, in hypogonadotropic hypogonadism, basal levels of alpha-subunit were significantly low and its response to LH-RH was barely detectable. The response of alpha-subunit to constant intravenous infusion of LH-RH (1 microgram/kg/h) was studied in 4 normal men. Both LH and alpha-subunit revealed biphasic patterns of elevation. Its releasing pattern suggests the possibility that two pools of gonadotropin are involved in the production and secretion of alpha-subunit. In patients with trophoblastic disease secreting low levels of hCG (18 mIU/ml), the responses of alpha-subunit as well as pituitary gonadotropin to LH-RH were normal. However, in cases of high concentrations of hCG (1000 mIU/ml), the responses of alpha-subunit and gonadotropin were suppressed. After the administration of LH-RH to a patient with an isolated ectopic alpha-subunit producing tumor, the serum concentration of pituitary gonadotropin increased within the normal range, although that of alpha-subunit did not show a significant change. These results suggest that the production of alpha-subunit by tumors may be autonomous in contrast with a regulatory production in the pituitary.

Adult↗
PubMed1982

[Studies on the regulatory mechanism of ovarian hCG receptors and placental luteotropin in rats (author's transl)].

The influences of exogenous hCG on rat (pseudopregnant and pregnant) ovarian hCG receptors and the presence of hCG-like material in the rat placenta were investigated. Ovarian hCG receptors in immature rats induced by PMS-hCG priming maintained a binding activity for about 20 days after hCG injection. The administration of hCG to pseudopregnant rats caused time and dose related changes in ovarian 125I-hCG binding percentage and the concentration of serum progesterone. The injection of hCG produced a slight decrease in the binding percentage and was followed by a marked decrease. The measurement of ovarian tissue hCG concentration by radioimmunoassay suggested that the initial loss of binding percentage was associated with the occupancy of receptors by the exogenous hCG, but the major loss of binding percentage might not be attributed to the receptor occupancy. The active process might be involved in the mechanism of receptor loss. The progesterone concentration in sera had a tendency to increase after the injection of 25IU hCG, while it decreased after the injection of 125IU hCG. The 125I-hCG binding percentage to ovaries and the serum concentration of progesterone reached their maximal values from mid to late pregnancy and declined as parturition approached. After the injection of hCG into pregnant rats, the binding percentage rapidly decreased and the serum concentration of progesterone increased. Thereafter the binding percentage recovered on the 4th day after the injection of hCG. On that day, though the concentration of hCG in ovarian tissue was barely detectable, the binding percentage was significantly low compared to the control level. The rat placenta (8th to 21st day of pregnancy) contained hCG-like activities, but they could not be detected in peripheral blood. In the treatment of hCG-antibody in pregnant rats, the binding percentage did not change but the serum concentration of progesterone showed a tendency to decrease to the control level. These studies show that hCG receptors exist as free sites in pregnant and pseudopregnant rat ovaries and may be regulated by down regulation after the treatment of large amounts of exogenous hCG. We found that hCG-like material in rat placenta determined by radioimmunoassay might serve as a luteotropin during pregnancy.

Animals↗
PubMed1982

Abortifacient effect and uterine cervix-dilating action of 16, 16-dimethyl trans delta 2 PGE1 methyl ester (ONO 802) in the form of a vaginal suppository (a randomized, double-blind, controlled study in the second trimester of pregnancy).

A newly synthesized 16, 16-dimethyl trans delta 2 PGE1 methyl ester (ONO 802) was clinically applied in the form of a vaginal suppository for therapeutic abortion of second trimester pregnancies. Its effects were studied in a double-blind test comparing it with an inactive placebo suppository. The study was conducted at 12 Japanese university hospitals. The number of patients was 125 in total, i.e. 63 receiving ONO 802 vaginal suppository (containing 1.0 mg ONO 802) and 62 receiving inactive placebo suppository. ONO 802 was more effective than placebo with a success rate of 87% (complete (71%) and incomplete (16%) abortions). The onset of uterine contractions was observed in 154.3+/-18.1 min. and the onset of uterine bleeding in 323.6+/-41.0 min. The expulsion of the fetus and placenta was observed in 955.4+/-97.0 and 961.6+/-97.0 min., respectively. The cervix dilating effect of ONO 802 was observed in 63.5% of the patients at 3 hours after the start of administration. Nausea, vomiting, abdominal cramps, diarrhea and pyrexia were noticed. However, all these side effects were transient and mild, requiring no treatment. No abnormality was observed in the puerperal course, duration of uterine bleeding or onset of subsequent menstruation following the therapeutic abortion. Therefore, the present study demonstrated that ONO 802 vaginal suppository was an effective and valuable drug for therapeutic abortion of second trimester pregnancies.

Abortifacient Agents↗
PubMed1982

Ovarian morphologic features and endocrine profile in amenorrheic patients.

Ovarian morphologic features and endocrine profile were investigated in 20 patients with primary amenorrhea and 41 patients with secondary amenorrhea. In light of macroscopic and microscopic findings, it was possible to distribute the anovulatory ovaries into the following six main types: (1) polycystic; (2) sclerotic; (3) normotrophied; (4) hypoplastic; (5) atrophic, and (6) streak. Anovulatory ovaries with or without follicles in an early developmental stage, such as the streak or hypoplastic type, were found in patients with primary amenorrhea. In contrast, ovaries with follicles in a late developmental stage, such as the polycystic, sclerotic and normotophied type, were seen in patients with secondary amenorrhea. A close correlation between ovarian morphologic features and hormonal parameters, such as serum FSH and LH levels, and the 24-hour urinary excretion of total estrogens was proved. From the present results, visualization of the ovaries and histologic examination of tissue obtained by biopsy might be an accepted part of the investigation of patients with primary and secondary amenorrhea, particularly those also complaining of infertility. It is no longer justified to postpone investigation until the infertile patients have proved their infertility over several years of a barren, marriage, and ovarian stimulation should be considered at an early stage.

Adult↗
PubMed1982

The characterization of alpha-subunit of glycoprotein hormone produced by undifferentiated carcinoma.

The glycoprotein hormone alpha-subunit was extracted and purified from the urine of a patient with undifferentiated carcinoma producing isolated alpha-subunit. Its final specific immunoactivity was 0.92 (mg alpha-subunit/mg protein). The alpha-subunit exhibited virtually identical immunoantigenicity to hCG-alpha antiserum with standard hCG-alpha. The molecular weight of the alpha-subunit determined by gel chromatography on Sephadex G-100 was greater than that of standard hCG-alpha dissociated by urea in vitro. By SDS disc electrophoresis, however, the alpha-subunit moved faster than hCG-alpha separated by mercaptoethanol reduction. The amino acid composition of the alpha-subunit was quite similar to that of standard hCG-alpha. In the isoelectric focusing, the major components of the alpha-subunit from undifferentiated carcinoma and the alpha-subunit from urine of normal pregnant women (third trimester) were distributed over the range from pH 3.5 to 6.0, while standard hCG-alpha was distributed in the fractions ranging from pH 6.0 to 8.0. The result of a combination study in vitro indicated that both alpha-subunits from undifferentiated carcinoma and from urine of normal pregnant women did not actively combine with hCG-beta. These results suggest that the alpha-subunit secreted by undifferentiated carcinoma is virtually identical with standard hCG-alpha as the protein moiety but differs in regard to carbohydrate moiety, and also suggest that the excess of alpha-subunit, which is not associated with beta-subunit, may have undergone some intracellular modification, and consequently, the electric charge of the freely secreted alpha-subunit changes and it no longer has the ability to combine with the beta-subunit.

Adult↗
PubMed1982

Multiple inhibitory effects of a luteinizing hormone-releasing hormone agonist on hCG-dependent steroidogenesis and on FSH-dependent responses in ovarian cells in vivo and in vitro.

[125I] labelled [D-Leu6, des-Gly-NH10(2)] LH-RH ethylamide (LH-RHa), when injected into immature female rats, bound specifically not only to the pituitary but also to the ovaries. LH-RHa inhibited hCG-stimulated progesterone production and ovarian weight augmentation in hypophysectomized immature female rats in vivo. FSH-induced ovarian hCG receptors and ovarian weight gain in diethylstilbestrol (DES)-treated hypophysectomized immature female rats were also suppressed by LH-RHa. Progesterone production by rat luteal cells in vitro was inhibited by LH-RHa. LH-RHa did not change the affinity or population of LH/hCG receptor in porcine granulosa cells in short term incubation. However, LH-RHa inhibited induction of LH/hCG receptor stimulated by FSH and insulin in long term culture of porcine granulosa cells. LH-RHa delayed hCG-stimulated cyclic AMP accumulation in porcine granulosa cells. These findings suggest that LH-RHa inhibits hCG-stimulated cyclic AMP accumulation and subsequent progesterone production as well as FSH-stimulated LH/hCG receptor induction by acting directly on ovarian cells.

Animals↗
PubMed1982

Scanning electron microscopic studies on stigmas in rat ovaries.

Ultrastructural observations on stigmas in rat ovarian follicles have been performed by scanning electron microscopy. Stigmas were classified into two types under a dissecting microscope; extensively bulging vesicles (bleb-type stigmas) and small, flat avascular areas (flat-type stigmas). The bleb-type stigma had lost its surface epithelial cells extensively, and the flattened and densely arranged fibroblasts without fibrous structures were exposed. These fibroblasts had short, serrate, cytoplasmic projections where multivesicular structure-like granules were seen. By contrast, on the flat-type stigma a small region of exposed stroma was covered with fibrous structures. Removal of the fibrous structures by the HCl-collagenase method revealed that the exposed stroma consisted of stellate fibroblasts surrounding a small opening through which a few granulosa cells were about to discharge. When the cumulus mass was protruding, it was surrounded by the fibrous structures. These findings indicate that both the stellate fibroblast formation and the presence of fibrous structures are needed for the release of ova through the stigma.

Animals↗
PubMed1982

[Discordance of competitive and non-competitive pregnancy tests for human chorionic gonadotropin, as related to alpha subunit producing tumor (author's transl)].

Ectopic production of isolated alpha subunit of glycoprotein hormones(s) in 32-year-old woman with metastatic lung tumor was first detected by a discordance in the immunological pregnancy tests for native human chorionic gonadotropin (hCG). Quantitative discrepancy of titrations among different types of pregnancy test kit, that i, competitive (hemagglutination or latex agglutination inhibition) and non-competitive (hemagglutination or latex agglutination) reactions, was also confirmed by the experimental study using highly purified ectopic alpha-subunit from the patient's urine. Thus, the discrepancy among the two types of assay systems was due by crossreaction of high concentrations (20,000 ng/ml) of ectopically secreted alpha-subunit of glycoprotein hormone(s). We report herein the typical behavior of immunological assay systems for native hCG in determining immunoreactive free hCG-alpha and stress the diagnostic value of the discordance observed in these assay systems.

Adult↗
PubMed1982

[Gonadotropin and plasma cyclic nucleotides].

Plasma cyclic nucleotides in some physiological conditions were measured in normal women and the changes of cyclic AMP were studied after the loading of gonadotropins in normal and castrated women. We demonstrated a circadian rhythm of cyclic AMP and its variation during menstrual cycle in normal women and also demonstrated its significant increase in pregnant women. But there was no significant variation of plasma cyclic GMP levels in those physiological conditions. Plasma cyclic AMP was increased by the simultaneous administration of HMG and HCG in both normal and castrated women. However, individual administration of HMG or HCG demonstrated that it was HCG that caused that increase in plasma cyclic AMP even in castrated women. To examine the extragonadal effects of HCG, cortisol, triiodothyronine (T3), thyroxine (T4) in the plasma were measured after the loading of HCG. The plasma cortisol level was influenced by HCG in neither normal nor castrated women. HCG did not cause any change of T3 or T4 in normal women; however it caused a marked increase in T3 with a small decrease in T4 in castrated women.

Chorionic Gonadotropin↗
PubMed1982

[Insulin Receptor in human placenta and its function].

Characteristic of insulin receptor in human placental villi with relation to glucose uptake and glycogenesis was studied in vitro. The specific binding of 125I-insulin to placental villi membranes was measured significantly higher in early placenta than in term placenta, while Scatchard plots analysis showed curvilinear, which indicated the binding affinity was approximately the same between them. However the binding capacity was higher in early placenta than in term placenta. The addition of insulin to placental villi in vitro showed increased glucose uptake, glycogen content and glycogen synthetase I form activity both in early and term placental villi. The glucose uptake, glycogen content and glycogen synthetase (total and I form) activity were higher in early placental villi than in term placental villi, but there was no significant difference in glycogen phosphorylase (total and active form). Collectively, the data suggest the presence of insulin receptor in placental villi varying its concentration with gestational age, where insulin plays a role in adjusting glucose uptake and glycogenesis.

Chorionic Villi↗
PubMed1982

[Failure of positive feedback in hypothalamo-pituitary-system in aged women and its recovery with estrogen treatment].

The positive feedback function of the hypothalamo-pituitary system in aging women was investigated by means of intravenous injection of conjugated estrogens. Marked LH surge was observed in both sexually mature young (20-35 y.o.) and premenopausal (35-49 y.o.) women after the intravenous injection of 20mg of conjugated estrogens. However, merely a small LH surge was observed in postmenopausal climacteric (50-55 y.o.) women, and no LH surge in aged (over 56 y.o.) women. In the patients with hypergonadotropic hypogonadism who are in the same age as sexually mature women, no LH surge was induced by conjugated estrogens. But positive feedback test done after oral administration of conjugated estrogens (1.25 mg/day) for 14 days showed positive reaction in both the aged women and the patients with hypergonadotropic hypogonadism in whom no LH surge had been observed before estrogen priming. The present results suggest that the dysfunction of positive feedback in aged women is mainly due to the decreased levels of estrogen produced by the ovaries but not the primary organic or functional changes of the hypothalamus or the pituitary.

Adult↗