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T Maruo

Publications and source records attributed to T Maruo.

At least 127 records · Page 7Linked to original sources

Increase in the expression of thyroid hormone receptors in porcine granulosa cells early in follicular maturation.

Thyroid hormone has been demonstrated to synergize with FSH to exert stimulatory effects on the differentiation of porcine granulosa cells. In order to further characterize the nature of thyroid hormone action on granulosa cells, the presence of triiodothyronine (T3) receptors in the nuclei of porcine granulosa cells was examined, and qualitatively and quantitatively compared during follicular maturation. Then, comparative abilities of granulosa cells from varying follicle stages to respond to T3 were assessed in terms of FSH-induced LH/hCG receptor formation and progesterone secretion. Furthermore, the expression of erb-A was analyzed using Northern blot hybridization of porcine granulosa cell RNA with a v-erb-A probe. Binding experiments with [125I]T3 showed that granulosa cell nuclei obtained from small follicles had a greater ability to bind [125I]T3 compared to those from large follicles. Scatchard analysis revealed the presence of nuclear T3 receptors with a single class of binding sites. There was little difference in the affinity of the T3 receptors during follicular maturation. By contrast, the number of the T3 receptors was higher in small follicle granulosa cells compared to that in large follicle granulosa cells. Thus, the increased T3 binding to small follicle granulosa cells relative to large follicle granulosa cells appears to be attributable to the increased number of the nuclear T3 receptors rather than to a change in the affinity. The magnitude of the stimulatory effects of T3 on granulosa cell functions was maximal in small follicle granulosa cells, but negligible in large follicle granulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of epidermal growth factor on the proliferation and differentiation of procine granulosa cells cultured in vitro].

Various growth factors are likely to be involved in the proliferation and differentiation of granulosa cells. Our previous studies revealed that insulin, insulin-like growth factor (IGF-I) and thyroid hormone each act as a biological amplifier of the action of FSH in the ovary. This study was undertaken to elucidate a possible direct effect of epidermal growth factor (EGF) on granulosa cell functions using the procine model. Porcine granulosa cells obtained from small, medium and large follicle, were cultured in the presence or absence of FSH and IGF-I, with or without EGF. EGF stimulated the proliferation of granulosa cells from small follicles, but did not affect the proliferation of granulosa cells from large follicles. In culture of granulosa cells obtained from large follicles. EGF inhibited the secretion of estradiol, and increased the secretion of progesterone by cultured cells. Scatchard analysis of 125I-EGF binding revealed that there is a single type of EGF receptor (EGF-R) in granulosa cells and that the number of EGF-R increases as the follicle matures. In Sephadex G-75 column chromatography of the medium following 5-day culture of porcine granulosa cells, an elution peak of immunoreactive EGF was found in the fraction similar to the elution of 125I-hEGF. These results suggested that EGF is produced by granulosa cells which contain abundant EGF-R. Thus, EGF is likely to act in an autocrine manner to stimulate the proliferation of less mature granulosa cells and to increase progesterone production by mature granulosa cells in association with an inhibitory action on estradiol production. These dual actions of EGF on granulosa cell function are of great interest.

Animals↗

[The role of signal transduction systems in the regulation of production and secretion of TA-4 by cultured cervical epidermoid carcinoma cells (CaSki)].

The CaSki cell line derived from an epidermoid carcinoma of the uterine cervix produces and releases a tumor associated-antigen, TA-4. The authors have already reported that EGF stimulated the production and secretion of TA-4 by the CaSki cells. EGF receptor is known to be one of the proteins phosphorylated by C-kinase. In order to elucidate a possible role of signal transduction systems (cAMP-A-kinase, diacyglycerol-C-kinase and Ca(2+)-calmodulin) in the regulation of TA-4 production and secretion by human cervical epidermoid carcinoma cells, the effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on TA-4 production and secretion by CaSki cells were evaluated. TA-4 in the cultured cells and media were measured with a SCC RIA-Kit. The addition of PMA or Ca2+ ionophore to the medium caused increases in the cellular levels of TA-4 and TA-4 levels in the medium in a dose-dependent manner shortly after the addition. Combined treatment with PMA and Ca2+ ionophore did not cause additive increases in TA-4 levels in the cells and medium compared to the treatment with PMA alone or Ca2+ ionophore alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

[The role of signal transduction systems in the regulation of the production and secretion of hCG (alpha, beta) by cultured human choriocarcinoma cells (BeWo)].

The BeWo cell line, derived from choriocarcinoma, produces and releases human chorionic gonadotropin (hCG) and its alpha- and beta-subunits. The authors have already reported that cAMP and EGF stimulated the production and secretion of hCG and its subunits by cultured BeWo cells. Therefore, in order to elucidate the role of signal transduction systems (cAMP-A-kinase system, DG-C-kinase system and Ca(2+)-calmodulin system) in the regulation of hCG (alpha, beta) synthesis by human choriocarcinoma cells, effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on hCG (alpha, beta) production and secretion by BeWo cells cultured in a serum-free condition were evaluated. Immunoreactive hCG alpha, hCG beta and hCG in the media and cultured cells were measured by each homologous RIA for hCG alpha, hCG beta and hCG, respectively. Addition of CT at a concentration of 100 ng/ml into the medium caused extreme increases in the cellular levels of hCG alpha, hCG beta and hCG together with remarkable increases in hCG alpha, hCG beta and hCG levels in the medium. This stimulatory effect of CT was first observed on the increase of hCG alpha levels in cultured BeWo cells and medium at 3h, then observed on the increase of hCG beta levels at 6h and was last detectable on the increase of hCG levels in the cultured cells and medium at 12h. Addition of PMA at a concentration of 100 ng/ml into the medium caused an increase in the cellular and medium levels of hCG alpha, hCG beta and hCG shortly (3h) after the exposure to PMA. Addition of A23187 at a concentration of 100 ng/ml into the medium caused a slight increase in hCG alpha levels in the medium at 6h without accompanying the increase in those cellular levels. When added together, PMA potentiated the stimulatory effect of CT on hCG alpha, hCG beta and hCG levels in the cultured BeWo cells and medium, while PMA did not potentiate the effect of A23187 in this experimental condition. These findings suggest that cAMP-A-kinase system plays a major role in the signal transduction of hCG (alpha, beta) synthesis and secretion by BeWo choriocarcinoma cells, and that DG-C-kinase system interacts synergistically with cAMP-A-kinase system in the regulation of hCG (alpha, beta) synthesis and secretion by BeWo cells. Ca(2+)-calmodulin system appears to participate in the regulation of hCG alpha secretion without affecting the synthesis of hCG (alpha, beta) in BeWo cells.

Calcimycin↗

Cytologic localization of epidermal growth factor and its receptor in developing human placenta varies over the course of pregnancy.

Cytologic localization of epidermal growth factor and its receptor in developing human placenta was analyzed by avidin-biotin immunoperoxidase techniques with a polyclonal antibody to epidermal growth factor and a monoclonal antibody to its receptor. In 4- to 5-week placenta, epidermal growth factor and its receptor were found to be almost exclusively localized to cytotrophoblasts, whereas in 6- to 12-week placentas they were predominantly localized to syncytiotrophoblasts. These findings suggest that both are initially expressed in cytotrophoblasts in very early placenta before 6 weeks' gestation and thereafter expressed in syncytiotrophoblasts in 6- to 12-week placentas. Their simultaneous expression in the cytotrophoblast of 4- to 5-week placentas and in the syncytiotrophoblast of 6- to 12-week placentas implies that epidermal growth factor may act in an autocrine manner in first-trimester placentas. By contrast, in second- and third-trimester placentas, epidermal growth factor was mainly localized to cytotrophoblasts, whereas its receptor was predominantly localized to syncytiotrophoblasts. These findings imply that epidermal growth factor may act in a paracrine fashion in second- and third-trimester placentas. The dynamic change in cytologic localization of epidermal growth factor and epidermal growth factor receptor in developing human placentas may reflect the change in a possible role of epidermal growth factor in the course of fetoplacental development.

Epidermal Growth Factor↗

Vascular reactivity in normal and abnormal gestation.

Preeclampsia is characterized by enhanced pressor responsiveness to angiotensin II. This report summarizes studies by our laboratory to investigate possible roles for calcium, sodium, membrane pumps, and the vasoactive hormones, atrial natriuretic peptide (hANP) and endothelin, in modulating the change in vascular reactivity characteristic of preeclampsia. Urinary calcium excretion, 1 alpha-25(OH)2D3 levels, and serum free calcium levels were all decreased, whereas parathyroid hormone levels and intraplatelet calcium concentrations were increased in women with preeclampsia. Erythrocyte sodium content was elevated, while red blood cell membrane Na-K-ATPase activity was decreased in patients with severe disease. Preeclamptics also had elevated levels of hANP, which failed to increase further when saline was infused or when blood pressure was increased transiently with angiotensin II administration. Finally, endothelin levels that are reduced in normal gestation, were increased in preeclampsia. While the cause of increased vascular reactivity is still unclear, there appear to be changes in the intracellular cation environment, combined with loss of compensating mechanisms, both at the membrane and humoral level, as well as enhanced concentrations of a potent vasoconstrictor in blood; all which lead to increases in vasoreactivity and blood pressure in preeclampsia.

Atrial Natriuretic Factor↗

Thyroid hormone as a biological amplifier of differentiated trophoblast function in early pregnancy.

Direct effects of T3 or T4 on the trophoblast function were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from normal early and term placentas were cultured with or without graded doses of T3 or T4 for 5 days in a serum-free condition. Addition of T3 (10(-8) mol/l) resulted in the maximum increase in daily secretion of progesterone, estradiol-17 beta as well as hCG alpha, hCG beta, hCG and hPL by cultured early placental tissues. Increases in progesterone and estradiol-17 beta secretion caused by the addition of T3 were further augmented in response to concomitant addition of pregnenolone and testosterone, respectively, suggesting that T3 (10(-8) mol/l) enhances 3 beta-hydroxysteroid dehydrogenase and aromatase activity in the placenta. These stimulatory effects of T3 (10(-8) mol/l) on the trophoblast endocrine function were also found with the use of T4 (10(-7) mol/l). Addition of higher or lower concentrations of T3 or T4 gave attenuated effects. These results suggest that the optimal concentration of thyroid hormone is needed for it to exert its maximally stimulatory action on trophoblast endocrine function. Unlike early placental tissues, cultured term placental tissues did not respond to the addition of T3 or T4 with increased endocrine activity. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of placental trophoblasts, followed by diminished expression of trophoblast endocrine function.

Chorionic Gonadotropin↗

Changes in causes of visual handicaps in Tokyo.

Newly registered visually handicapped patients at the Tokyo Metropolitan Rehabilitation Center for the Physically and Mentally Handicapped were studied in 1968 (when the facility was opened), 1978, and 1988. Examinations were carried out by the same physicians and diagnoses were made by uniform criteria. Since approximately 10% of the total population of Japan lives in Tokyo, the statistics on the causes of visual handicaps in this area deserve to be reported. The changes observed over the past twenty years are as follows: There were few changes in the percentages of high myopia, retinal degeneration and senile cataract. The percentages of corneal opacity, retinopathy of prematurity, congenital cataract and optic atrophy decreased, while those of diabetic retinopathy, glaucoma and retinal macular degeneration increased. Advances in medical treatment and the shift into an aging society in Japan are responsible for these changes observed.

Adolescent↗

[Modification of endocrine function of trophoblasts by thyroid hormone].

Direct effects of L-triiodothyronine(T3) on placental endocrine function were investigated in vitro with an organ culture system for human placental tissues. Explants of trophoblastic tissues obtained from early and term placentas were cultured with or without graded doses of T3 in a serum-free condition. The addition of an optimal concentration of T3(10(-3) M T3) stimulated daily secretion of progesterone and estradiol from cultured early placental tissues by acting at the level of 3 beta-hydroxysteroid dehydrogenase and aromatase enzyme activity, together with the enhancement of hCG(alpha, beta) and hPL secretion. The addition of higher or lower concentrations of T3 gave attenuated effects and the addition of an excessive concentration of T3(10(-3) M T3) resulted in remarkable inhibition of progesterone and estradiol secretion by cultured early placental tissues. These results suggest that the optimal concentration of thyroid hormone acts as a biological amplifier of endocrine function of cultured trophoblasts obtained from early placentas. Unlike the early placental tissues, cultured term placental tissues did not respond to the addition of graded doses of T3 with increased endocrine function. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of the trophoblast, followed by diminished endocrine function of early placental trophoblasts.

Chorionic Gonadotropin↗

Long-term results after strabismus surgery.

The results of surgery after 4 years' or more postoperative follow-up have been evaluated in a total of 1031 cases (575 esotropia, 456 exotropia). There is a difference in the angle of strabismus 1 month after surgery and 4 years after surgery. Based on these findings, the results of strabismus surgery must be evaluated after a sufficient amount of time has passed. The angle of strabismus to be aimed at, to provide best binocular vision and patient satisfaction, should be in the range of -2 +7 degree for esotropia and +2 -10 degree for exotropia, regardless of the patient's age at surgery.

Age Factors↗

Penetration of fleroxacin into maxillary sinus mucosa and palatine tonsil.

Ten patients undergoing tonsillectomy or operation on the maxillary-antrum were given 200 mg fleroxacin orally 1-2 h before surgery. The concentration of fleroxacin in maxillary sinus mucosa (mean 2.61 mg/kg) was similar to that in serum samples collected simultaneously (mean 2.46 mg/l); and similar results were obtained with tonsillar tissue (mean 3.27 mg/kg; simultaneous serum samples, mean 2.84 mg/l).

Anti-Infective Agents↗

Comparison of the facilitative roles of insulin and insulin-like growth factor I in the functional differentiation of granulosa cells: in vitro studies with the porcine model.

The facilitative effects of insulin and IGF-I were compared in vitro with regard to induction of differentiated functions of porcine granulosa cells. The monolayers were maintained under serum-free conditions in the absence or presence of porcine FSH (20 micrograms/l), with or without graded doses of insulin or IGF-I. Concurrent treatment with IGF-I and FSH produced morphological differentiation and augmented LH/hCG receptor binding together with an enhancement in progesterone and estradiol secretion relative to treatment with FSH alone. IGF-I alone was incapable of exhibiting these effects. Insulin synergized with FSH to facilitate the granulosa cell functions except estradiol secretion. Maximal effective dose of IGF-I was 100 micrograms/l which is within the physiological concentration in vivo, whereas that of insulin was 1.0 mg/l, which is 1000-fold higher than the physiological level. Although the maximal effective doses of IGF-I and insulin produced a comparable increment in progesterone secretion and LH/hCG receptor induction, combined treatment with IGF-I and insulin did not prove additive. [125I]IGF-I binding revealed that specific IGF-I receptors with two classes of binding sites are present on porcine granulosa cells. No distinct differences were detected between IGF-I receptors of granulosa cells from small, medium and large follicles. Insulin was approximately 100-fold less active than IGF-I in competing for [125I]IGF-I binding. These findings suggest that porcine granulosa cells possess specific IGF-I binding sites which may mediate the cytodifferentiative actions of insulin-like peptides. Since IGF-I is more potent than insulin in amplifying the actions of FSH and maximally exerts the cytodifferentiative effects at the physiological concentration, it is likely that IGF-I plays the more important role in granulosa cell differentiation in synergy with FSH.

Animals↗

[Immunohistochemical studies on epidermal growth factor receptor and the myc oncogene product in squamous cell carcinoma of the uterine cervix].

Recent studies have demonstrated that the amount of epidermal growth factor receptor (EGF-R) is increased in squamous cell carcinoma cells and that the amino acid sequence of EGF-R shows great homology with the v-erb B transforming protein. In this study, we examined the tissue localization of EGF-R and myc oncogene product in normal squamous epithelium, dysplasia, carcinoma in situ, invasive squamous cell carcinoma of the uterine cervix and in metastatic lymph nodes by means of the avidin/biotin immunoperoxidase technique. Normal squamous epithelium was negative for EGF-R and myc product. The lesions of dysplasia and carcinoma in situ had a positive staining for EGF-R, but were still negative for myc product. There were differences in the staining intensity of EGF-R and myc product among the types of invasive carcinoma. Staining for EGF-R and myc product was negative in small cell non-keratinizing carcinoma, whereas strong staining for both EGF-R and myc product was observed in large cell non-keratinizing and keratinizing carcinoma. The intensity of positive staining for EGF-R and myc product declined in the lesions of cancer pearl. Metastatic lymph nodes were remarkably stained for EGF-R and myc product, while non-metastatic lymph nodes were negative for EGF-R and myc product. Our observations suggest that the amplified expression of EGF-R and myc product may accompany the malignant transformation of squamous epithelium of the uterine cervix, together with the metastasis.

Carcinoma, Squamous Cell↗

[Effect of thyroid hormone on steroidogenic enzyme induction in porcine granulosa cells cultured in vitro].

In order to elucidate the mechanism of thyroid hormone action on the ovary, direct effects of L-thyroxine (T4) or L-triiodothyronine (T3) on steroidogenic enzyme induction were investigated in vitro using a monolayer culture system of porcine granulosa cells obtained from small follicles. The cells were cultured in the absence or presence of porcine FSH (20ng/ml) for 6 days, with or without T4 or T3, under sparsely (4%) serum supplemented condition. The mechanism of thyroid hormone action on the granulosa cells was studied by testing the capability of thyroid hormone to enhance the steroidogenesis in response to exogenously provided substrates. Concomitant treatment with FSH (20ng/ml) and T4 (10(-7) M) caused a further increased production of progesterone in response to the addition of pregnenolone compared to that in the absence of pregnenolone. The same treatment with FSH and T4 also caused a further increased production of estrone in response to the addition of androstenedione. Concomitant treatment with 10(-9) MT3 demonstrated similar stimulatory effects on the steroidogenesis in cultured granulosa cells. T4 or T3 alone without FSH was incapable of exhibiting these stimulatory effects. Furthermore, aromatase activity in cultured granulosa cells assessed by the release of tritiated water from [1 beta-3H, 4-14C] androstenedione was significantly higher in the cells treated concomitantly with FSH (20ng/ml) and T4 (10(-7) M) than that in the cells treated with FSH alone. These results suggest that thyroid hormone synergizes with FSH and increases FSH-mediated induction of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and aromatase activity in immature granulosa cells. Since the effective dose of T4 and T3 observed in our studies is in the physiological range of circulating total levels of T4 and T3, it can be concluded that the synergism between FSH and thyroid hormone is of physiological importance to the full expression of FSH actions in the functional differentiation of immature granulosa cells.

3-Hydroxysteroid Dehydrogenases↗

Immunohistochemical localization of epidermal growth factor receptor and myc oncogene product in human placenta: implication for trophoblast proliferation and differentiation.

Cytologic localization of epidermal growth factor receptor and myc oncogene protein product in developing human placenta was analyzed by avidin/biotin immunoperoxidase techniques with a monoclonal antibody to epidermal growth factor receptor and an affinity purified polyclonal antibody to myc protein product. Epidermal growth factor receptor was found to be almost exclusively localized to syncytiotrophoblast, paralleling the immunohistochemical localization of human chorionic gonadotropin. Since epidermal growth factor has been shown to stimulate human chorionic gonadotropin and human placental lactogen production by cultured early placental tissue, the present finding that epidermal growth factor receptor was localized to mitotically inactive syncytiotrophoblast suggests a role for epidermal growth factor receptor in the induction of differentiated function of trophoblast rather than trophoblast proliferation. By contrast, myc protein product was found to be predominantly localized to cytotrophoblastic cells, paralleling the autoradiographic distribution of replicating cytotrophoblast identified by tritiated thymidine labeling of placental explant. A close similarity between the cytologic localization of myc protein product and tritiated thymidine labeling of placental explant suggests that myc protein expression is linked to trophoblast proliferation. Furthermore, immunohistochemical cellular levels of both epidermal growth factor receptor and myc protein product were most pronounced in early placenta and declined in term placenta. Thus myc protein product and epidermal growth factor receptor seem to play a crucial role in the induction of trophoblast proliferation and differentiation, respectively, during the development of human placenta.

ErbB Receptors↗