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Biomedical subjects

T Maruo

Publications and source records attributed to T Maruo.

At least 109 records · Page 6Linked to original sources

Stage-limited expression of myc oncoprotein in the human ovary during follicular growth, regression and atresia.

The cytologic localization and cellular levels of myc oncoprotein in the human ovary during follicular growth, regression and atresia were examined by the avidin/biotin immunoperoxidase method with a specific antibody to myc oncoprotein. In primordial follicles, only the oocyte showed intense immunostaining for myc protein, whereas the granulosa cells were negative for the staining. In preantral follicles, both the oocyte and granulosa cells were moderately immunostained for myc protein. In antral and preovulatory follicles, there was no appreciable staining for myc protein in the granulosa or theca cells, while myc protein staining in the oocyte persisted with less intensity. It is of interest that myc protein expression in granulosa cells was apparent only during the preantral follicle stage. Corpora lutea during the early and mid luteal phase were negative for myc protein staining, whereas in regressing corpora lutea during the late luteal phase, peripheral theca lutein cells adjacent to the central core of scar tissue were immunostained for myc protein. Corpora albicans showed no staining for myc protein. In atretic follicles, granulosa cells and theca interna cells demonstrated positive staining for myc protein. Ovarian stromal cells were negative for the immunostaining throughout the menstrual cycle. This demonstrates that myc protein is expressed in a stage-limited manner in the human ovary during follicular growth and regression. The abundant expression of myc protein in the oocyte at the primordial and preantral follicle stages and in the granulosa cells at the preantral follicle stage suggests a role for myc expression in the initial growth of the oocyte as well as in the autonomous growth of granulosa cells during the preantral stage seemingly independent of gonadotropic stimulation. Furthermore, notable expression of myc protein in the granulosa cells and theca interna cells of atretic follicles and in the peripheral theca lutein cells of regressing corpora lutea implies the possible participation of myc expression in remodelling the ovarian local tissue following atresia and luteolysis in the human ovary.

Adult↗

Stage-specific expression of c-myc messenger ribonucleic acid in porcine granulosa cells early in follicular growth.

In the present study, the expression of c-myc mRNA in porcine granulosa cells harvested from varying follicle stages was analyzed using northern blot hybridization with a c-myc probe, and compared during follicular growth. Northern blot analysis revealed that porcine granulosa cell RNA obtained from small (1-2 mm) follicles contained an abundance of c-myc transcript of 2.4 kb, the size of which was identical to the c-myc transcript obtained with human early placental RNA used as the control. In contrast to small-follicle granulosa cell RNA, total RNA preparations from either medium (3-5 mm)-follicle granulosa cells or large (6-11 mm)-follicle granulosa cells exhibited no detectable transcripts with the c-myc probe. These results suggest that expression of c-myc mRNA in porcine granulosa cells is limited only at the early stage of follicular growth. The stage-specific expression of c-myc mRNA in granulosa cells early in follicular growth may play a physiological role in the autonomous growth of immature granulosa cells in early folliculogenesis, seemingly independent of pituitary gonadotropic stimulation.

Animals↗

[Treatment of paralytic strabismus].

1) Cases of strabismus combined with abnormalities in ocular movement were divided into three groups: paralytic nonconcomitant strabismus, special forms of strabismus, and paralytic concomitant strabismus. 977 cases of surgery for paralytic nonconcomitant strabismus were analyzed. 2) 109 cases of surgery for paralytic esotropia due to abducens palsy were performed. In cases of complete paralysis, a transposition of the vertical rectus muscle was indicated. In cases of incomplete paralysis, a resection of the lateral rectus muscle was indicated. On the basis of these indications, the same results could be achieved, and when a recession of the medial rectus muscle was concurrently performed the results were improved. 3) In oculomotor palsy, 138 cases of surgery for paralytic exotropia were performed. In cases of complete paralysis, a transposition of the superior oblique muscle was indicated. In cases of incomplete paralysis, a resection of the medial rectus muscle was indicated. On the basis of these indications, the same results could be achieved, and when a recession of the lateral rectus muscle was concurrently performed the results were improved. 4) 570 cases of surgery for superior oblique muscle palsy were performed. In cases of vertical deviation, a weakening operation on the inferior oblique muscle, the superior rectus muscle of the affected eye, and the inferior rectus muscle of the sound eye were indicated. In cases of torsional deviation, good results were obtained through an advancement of the anterior part of the superior oblique muscle and a resection of the superior oblique muscle. 5) Statistics concerning cure based on the standards for cure employed by the Japanese Association of Strabismus and Amblyopia, or from the point of view of cosmetic cure were: 85% for paralytic esotropia and superior oblique muscle palsy, 82% satisfactory for incomplete paralysis of the oculomotor nerve within paralytic exotropia, and 61% relatively unsatisfactory for complete paralysis of the oculomotor nerve within paralytic exotropia. 6) The results of 216 cases examined after period of four years or longer were: cases where a one-month postoperative cure or cosmetic cure was maintained over this period were 90% of superior oblique muscle palsy cases, 79% of paralytic esotropia, and 59% of paralytic exotropia. Paralytic exotropia showed poor results. The surgical methods were muscle transposition in cases of horizontal muscle surgery and surgery of the oblique muscles in cases of vertical muscle surgery. 7) Through the Turn-Amplitude Analysis of the amounts of EMG interference patterns in the extraocular muscle, neuropathy was classified as either complete or incomplete.(ABSTRACT TRUNCATED AT 400 WORDS)

Child, Preschool↗

[Insulin-like growth factor-I (IGF-I) as a local regulator of proliferation and differentiation of villous trophoblasts in early pregnancy].

In order to elucidate the role of insulin-like growth factor-I (IGF-I) in human placental growth and function, the effects of IGF-I on the proliferation and differentiation of villous trophoblasts were investigated in vitro using an organ culture system of human early placental tissues. Explants of trophoblastic tissues obtained from 4-5 week and 6-12 week placentas were cultured with or without IGF-I (1 ng/ml, 100 ng/ml), in the presence or absence of 10(-8) M triiodo-L-thyronine (T3) respectively, in a serum-free condition. The possible effect IGF-I on the proliferative activity of the cells was examined by immunocytochemical techniques with a monoclonal antibody to proliferating cell nuclear antigen (PCNA), while the possible effect of IGF-I on the differentiated function was assessed by determining the ability to secrete hCG and hPL. In the 4-5 week placentas, IGF-I and IGF-I receptor were almost exclusively localized in cytotrophoblasts and IGF-I augmented the proliferative activity of cytotrophoblasts without affecting the ability to secrete hCG and hPL. By contrast, in the 6-12 week placentas, IGF-I and IGF-I receptor were localized in both cytotrophoblasts and syncytiotrophoblasts and IGF-I stimulated the secretion of hCG and hPL following the enhancement of the proliferative activity of cytotrophoblasts. In column chromatography of the serum-free medium obtained following a 5-day culture of trophoblasts, an elution peak of immunoreactive IGF-I was found in the fractions similar to the elution of 125I-IGF-I. The eluted amount of immunoreactive IGF-I was increased by the addition of 10(-8) MT3 to the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗

Decreased expression of epidermal growth factor and its receptor in the malignant transformation of trophoblasts.

BACKGROUND: Gestational trophoblastic neoplasms comprise the neoplastic spectrum of nonmalignant hydatidiform mole, invasive hydatidiform mole, and truly malignant choriocarcinoma. Increasing evidence indicates that epidermal growth factor (EGF) acts as an enhancer of trophoblast function to produce human chorionic gonadotropin and that EGF and its receptor may provide a growth advantage to certain carcinoma cells. The current study was undertaken to evaluate a possible link between malignant transformation of trophoblast and expression of EGF and EGF receptor. METHODS: Cytologic localization and cellular levels of expression of EGF and EGF receptor in hydatidiform mole, invasive hydatidiform mole, and choriocarcinoma tissue specimens were examined by the avidin-biotin immunoperoxidase techniques with monoclonal antibodies against EGF and EGF receptor. RESULTS: EGF in hydatidiform mole and invasive mole was localized in syncytiotrophoblasts, whereas cytologic localization of EGF receptor in hydatidiform mole and invasive mole was observed in both cytotrophoblasts and syncytiotrophoblasts. By contrast, EGF and EGF receptor in choriocarcinoma were exhibited in cytotrophoblastic and syncytiotrophoblastic elements. Most (72%) hydatidiform moles immunostained intensely for EGF and EGF receptor, whereas most (78%) choriocarcinomas immunostained slightly for EGF and EGF receptor. Invasive mole occupied the middle position in the staining intensity for EGF and EGF receptor, between hydatidiform mole and choriocarcinoma, with 50% of the cases exhibiting moderate staining. CONCLUSIONS: The simultaneous expression of EGF and EGF receptor in the neoplastic trophoblasts implies that EGF may act in an autocrine-paracrine manner in trophoblastic neoplasms. Furthermore, the results obtained suggest that cytologic expression of EGF and EGF receptor in trophoblastic neoplasms decreases in the malignant transformation of trophoblast.

Cell Transformation, Neoplastic↗

Return of fertility after the removal of intrauterine devices: a comparison of inert and copper bearing devices.

The use of intrauterine device (IUD) has been suspected to be linked to involuntary infertility due to increased risk of pelvic inflammatory diseases. Nevertheless, it remains unclear whether the overall risk of infertility after discontinuing use of IUD increases with the duration of IUD use. Thus, the present study was designed to evaluate the return of fertility after discontinuing use of copper containing IUDs compared to inert IUD and to determine a possible relationship between the length of IUD use and return of fertility. Ninety women with Lippes Loop type D (LL), 88 women with Copper-T200 (TCu-200) and 83 women with Multiload Copper-250 (MLCu-250) were included in the analysis. The life table analysis and log rank-test showed that TCu-200 and MLCu-250 acceptors had a more rapid return of fertility compared to LL acceptors, although there was no significant difference in the return of fertility between TCu-200 and MLCu-250 acceptors. Compared to LL acceptors, the net cumulative probability of pregnancy after discontinuing use of IUD was 3 times higher in copper containing IUD acceptors in the first 3 months and somewhat higher in the first 4 to 11 months after removal of IUD. The length of use in copper containing IUDs (TCu-200 and MLCu-250) acceptors did not influence the return of fertility, whereas the return of fertility after removal of inert IUD (LL) was significantly higher in case of the use for shorter than 48 months compared to the use for longer than 48 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Expression of epidermal growth factor and its receptor in the human ovary during follicular growth and regression.

Immunohistochemical studies were performed using specific antibodies to epidermal growth factor (EGF) and EGF receptor to determine their presence and cellular localization in the human ovary during follicular growth and regression. There was no immunostaining for EGF or EGF receptor in primordial follicles. In the preantral follicle stage, immunostaining for EGF and EGF receptor was observed only in the oocyte. The staining intensity of the oocyte increased as the oocyte reached the preovulatory stage. In the antral follicle stage, immunostaining for EGF and EGF receptor became apparent in the granulosa and theca interna cell layers, without appreciable staining in the surrounding stromal cells. The immunostaining for EGF and EGF receptor in the granulosa cells and theca interna cells persisted in preovulatory follicles and corpus luteum, and intensified in the midluteal phase. The stromal cells surrounding the corpus luteum were negative for EGF and EGF receptor staining. In the regressing corpus luteum, immunostaining for EGF and EGF receptor was present in the peripheral lutein cells adjacent to the central core of scar tissue, but absent in the scar tissue of the central core. Corpus albicans showed no staining for EGF and EGF receptor. By contrast, the stromal cells surrounding the corpus albicans in the cortex region demonstrated intense staining for EGF and EGF receptor, while the stromal cells surrounding the corpus albicans in the medullary region were negative for immunostaining. In the case of atretic follicles, the theca interna cells showed intense staining for EGF and EGF receptor, but immunostaining in the scattered granulosa cells was negligible. This is the first study to demonstrate a remarkable change in the expression of EGF and EGF receptor in the oocyte, granulosa cells, thecal cells, and surrounding stromal cells over the course of follicular growth and regression. The results obtained support EGF participation in oocyte maturation and in follicular growth and atresia. The intense immunostaining for EGF and EGF receptor observed in the theca interna cells in atretic follicles and the stromal cells surrounding corpus albicans in the cortex region raises the possibility of EGF involvement in transformation of thecal cells into stromal cells. Furthermore, the cell type-specific simultaneous expression of EGF and EGF receptor in follicular and stromal compartments in the various stages of follicular development suggests that an autocrine mode of EGF action may exist to regulate follicular growth and regression in the human ovary.

Adult↗

Altered expression of insulin and insulin-like growth factor-I receptors in follicular and stromal compartments of polycystic ovaries.

In the ovary, insulin and insulin-like growth factor-I (IGF-I) act synergistically with FSH to augment estrogen production by granulosa cells and with LH to augment androgen production by thecal stromal cells. It is also evident that insulin resistance is common in patients with polycystic ovary syndrome (PCO). Thus, in the present study we investigated the expression of insulin and IGF-I receptors in PCO ovaries and compared them with those in normal ovaries. Ovarian tissues were obtained from four PCO patients undergoing wedge resection, and from six patients who underwent radical hysterectomy. Immunohistochemical staining for insulin and IGF-I receptors was performed by avidin/biotin immunoperoxidase techniques. In normal ovaries, the expression of insulin and IGF-I receptors in follicular compartment became apparent in the preantral follicle stage and augmented with the follicular growth, while the stromal cells, regardless of the follicle stage, possessed insulin and IGF-I receptors. In PCO ovaries associated with hyperinsulinemia, no expression of insulin receptors was detected in granulosa or thecal stromal cells, while IGF-I receptor expression increased in thecal stromal cells but decreased in granulosa cells compared to those in normal ovaries. However, in PCO ovaries from patients without hyperinsulinemia, insulin receptor expression was apparent in both granulosa and thecal stromal cells, with a similar intensity to that observed in normal ovaries, while IGF-I receptor expression was negligible in granulosa cells but sustained in thecal stromal cells. These findings suggest that decreased expression of insulin receptors in PCO ovaries associated with hyperinsulinemia may be secondary to receptor down regulation, whereas defective expression in granulosa cells along with elevated or persisted expression in thecal stromal cells of IGF-I receptors may be common in PCO ovaries and contribute to the endocrine profiles of PCO in which varying degrees of hyperandrogenism is a predominant feature.

Adult↗

Insulin receptor expression in follicular and stromal compartments of the human ovary over the course of follicular growth, regression and atresia.

The cytologic localization and cellular levels of insulin receptors in the human ovary during follicular growth, regression and atresia were examined by the avidin/biotin immunoperoxidase techniques with a monoclonal antibody to insulin receptor. In primordial follicles, only the oocyte showed a weak immunostaining for insulin receptor, whereas the stromal cells surrounding primordial follicles were moderately immunostained. The earliest stage of follicular growth at which immunostaining for insulin receptor in granulosa cells and theca interna cells became apparent was the preantral stage. With the increase in the size of the follicles, the immunostaining of the oocyte and follicular elements intensified, whereas the staining intensity of the stromal cells surrounding growing follicles was reduced compared to those surrounding primordial follicles. The immunostaining in granulosa and theca interna cells persisted in the corpus luteum, and further intensified during the midluteal phase. In the regressing corpus luteum, the immunostaining was present only in the peripheral lutein cells adjacent to the central scar tissue. The corpus albicans was negative for the immunostaining, but the surrounding stromal cells exhibited predominant staining. In atretic follicles, the theca interna cells exhibited intense staining for insulin receptor without appreciable staining in the scattered granulosa cells, whereas the surrounding stromal cells were moderately immunostained. This is the first study to demonstrate notable changes in insulin receptor expression in the oocyte, granulosa cells, theca cells, lutein cells and surrounding stromal cells during follicular growth, regression and atresia. The results obtained indicate insulin participation in oocyte maturation, follicular growth and stromal cell function. The increased expression of insulin receptors in theca interna cells of atretic follicles and in stromal cells surrounding the corpora albicans raises the intriguing possibility of insulin involvement in the transformation of theca interna cells into stromal cells. This implies that insulin may participate in remodelling ovarian local tissues following follicular atresia and luteolysis in the human ovary.

Adult↗

Human early placental trophoblasts produce an epidermal growth factor-like substance in synergy with thyroid hormone.

Previous studies have shown that human trophoblast is the site of epidermal growth factor (EGF) localization, reception and action and that thyroid hormone exerts similar effects on trophoblasts endocrine function as observed with EGF. Thus, the present study was designed to examine local production of an EGF-like substance in synergy with thyroid hormone by early placenta. Explants of normal early (7-8 weeks) placentas were cultured in a serum-free condition in the presence or absence of L-triiodothyronine (T3), with or without cycloheximide for 4 days. The conditioned media were dialyzed, lyophilized, acidified and chromatographed over a Sephadex G-75 column equilibrated with 1 mol/l acetic acid. EGF was measured by a specific RIA for human EGF. Fractionation of the serum-free conditioned media resulted in the elution of immunoreactive EGF with an apparent molecular weight of 9,000 which is larger than [125I] human EGF. The addition of T3 (10(-8) mol/l) resulted in increased secretion of immunoreactive EGF by placental explants. By contrast, the addition of cycloheximide (5 x 10(-5) mol/l) dramatically reduced the secretion of immunoreactive EGF. The similarity of the immunoreactive EGF material to authentic human EGF was supported by parallel displacement in human EGF-RIA. These results suggest that human early placental trophoblast is capable of producing an EGF-like substance and that thyroid hormone enhances the local production of the EGF-like substance. This suggests that an autocrine/paracrine control system, wherein EGF serves as the signal in regulating placental growth and function in synergy with thyroid hormone, exists in human early placenta.

Chromatography, Gel↗

[Epidermal growth factor regulates trophoblast proliferation and differentiation in an autocrine/paracrine manner].

Effects of epidermal growth factor (EGF) on the expression of trophoblast proliferation and differentiation were investigated in vitro using an organ culture system of human placental tissues. Explants of trophoblastic tissues obtained from each trimester of gestation were cultured with or without EGF (100 ng/ml) in serum-free conditions. In order to determine the possible effect of EGF on the proliferation activity of villous trophoblasts, immunostaining with monoclonal antibody Ki-67 was used. On the other hand, the possible effect of EGF on the differentiated cellular function of villous trophoblasts was assessed by determining the ability to secrete hCG and hPL. In 4-5 week placenta, EGF and EGF receptor were found to be almost exclusively localized in cytotrophoblasts and EGF enhanced the proliferation of cytotrophoblasts without affecting the ability to secrete hCG and hPL, whereas in 6-12 week placenta, EGF and EGF receptor were predominantly localized in syncytiotrophoblasts and EGF stimulated the secretion of hCG and hPL without affecting the proliferation of cytotrophoblasts. These findings suggest that EGF has dual actions which independently affect trophoblast proliferation and differentiation in the first trimester of gestation in an autocrine manner. But, in the second and third trimesters of gestation, EGF mediates the expression of placental function in a paracrine manner.

Cell Differentiation↗

[Biology of trophoblast and its endocrinological profiles].

The trophoblast of human placenta is composed of syncytiotrophoblast (S-cell) and cytotrophoblast (C-cell). C-cell displays proliferative properties, while S-cell displays little potential for proliferation. A close similarity between cytologic localization of myc product and [3H]thymidine labeling suggests that myc expression is linked to trophoblast proliferation. In situ hybridization with cDNA probes revealed that mRNA expression of hCG alpha and hCG beta are initiated before syncytial formation, whereas hPL mRNA is expressed only in fully differentiated S-cell. EGF and EGF receptor (EGF-R) in 4-5 weeks placenta were localized to C-cell, whereas EGF and EGF-R in 6-12 weeks placenta were localized to S-cell. Consistent with these findings, EGF exerted gestational age dependent dual action on early placenta: one was to stimulate trophoblast proliferation in 4-5 weeks placenta and the other was to stimulate differentiated trophoblast function in 6-12 weeks placenta. An optimal dose of thyroid hormone stimulated progesterone, estradiol, hCG and hPL production in early placental tissues. Furthermore, women with unfavorable outcome of threatened abortion had lower T4, T3, free T4 and free T3 levels, as compared to women with favorable outcome. These data imply a role for thyroid hormone in maintaining early pregnancy. On the other hand, progesterone selectively inhibited hCG (alpha, beta) mRNAs expression and decreased hCG secretion in normal placental tissues, whereas choriocarcinoma did not respond to progesterone. This suggests that inhibitory regulation of hCG synthesis in choriocarcinoma is different from normal placenta. Characterization of choriocarcinoma hCG revealed that there are striking differences in carbohydrate structures between normal hCG and choriocarcinoma hCG. Sialic acid content in choriocarcinoma hCG was extremely lower compared to that in normal hCG. The biochemical detection of the alteration in hCG sugar chains is useful for early diagnosis of choriocarcinoma.

Cell Differentiation↗

Immunohistochemical demonstration of elevated expression of epidermal growth factor receptor in the neoplastic changes of cervical squamous epithelium.

To evaluate epidermal growth factor (EGF) receptor expression in the neoplastic process of squamous cell epithelium of the uterine cervix, normal, premalignant, and malignant cervical tissues were examined for the presence of EGF receptor by the avidin-biotin immunoperoxidase techniques with a monoclonal antibody to EGF receptor. Although normal cervical epithelium did not show appreciable staining for EGF receptor, predominant staining for the receptor was observed in most dysplastic epithelia and carcinomas in situ. In invasive squamous carcinoma, there was a great difference in the immunohistochemically detected levels of EGF receptor among the histologic cell types. Large cell nonkeratinizing carcinoma and its keratinizing counterpart contained high levels of EGF receptor; small cell nonkeratinizing carcinoma lacked immunostainable EGF receptor. These results suggest that the elevated expression of EGF receptor may be involved in the initial stage of tumorigenesis of cervical squamous epithelium and that EGF receptor expression may be related to the differentiation or dedifferentiation of cervical squamous carcinoma cells.

Antibodies, Monoclonal↗

A novel change in cytologic localization of human chorionic gonadotropin and human placental lactogen in first-trimester placenta in the course of gestation.

Cytologic localization of human chorionic gonadotropin and human placental lactogen in developing human early placenta was analyzed by avidin-biotin immunoperoxidase techniques with an affinity-purified polyclonal antibody to beta-human chorionic gonadotropin carboxyl terminal peptide and a polyclonal antibody to human placental lactogen. In 4- to 5-week placentas human chorionic gonadotropin and human placental lactogen were found to be primarily localized to cytotrophoblasts, whereas in 6- to 12-week placentas these substances were exclusively localized to syncytiotrophoblast. We previously reported that a similar change in cytologic localization of epidermal growth factor and its receptor from cytotrophoblasts to syncytiotrophoblast in first-trimester placenta appeared between 5 and 6 weeks of gestation. Because epidermal growth factor was demonstrated to stimulate human chorionic gonadotropin and human placental lactogen production by early placental tissues, their simultaneous expression, as well as epidermal growth factor and its receptor in the cytotrophoblast of 4- to 5-week placenta and in the syncytiotrophoblast of 6- to 12-week placenta, implies that human chorionic gonadotropin and human placental lactogen production by first-trimester placenta may be regulated in an autocrine manner, wherein epidermal growth factor may serve as the signal. These findings suggest that in very early placenta, before 6 weeks of gestation, no sequential expression of human chorionic gonadotropin and human placental lactogen closely linked to syncytia formation may exist and that both can be expressed in the cytotrophoblast or undifferentiated stem cell of villous trophoblast in very early placenta.

Chorionic Gonadotropin↗

A role for thyroid hormone in the induction of ovulation and corpus luteum function.

We have previously demonstrated that thyroid hormone synergizes with follicle-stimulating hormone (FSH) to exert stimulatory effects on granulosa cell differentiation and function, suggesting that it plays a physiological role in amplifying FSH-mediated differentiation of granulosa cells. The adequate differentiation of these cells, followed by normal follicle development, is indispensable for ovulation and subsequent corpus luteum formation. Thus, in the present studies, the clinical implications of thyroid hormone in the induction of ovulation and corpus luteum function were investigated. Serum levels of total 3,5,3'-triiodothyronine (T3) and total thyroxine (T4) as well as free T3 and T4 were significantly lower in patients with weight loss amenorrhea compared to normal cycling women. Although no ovulation was induced by clomiphene therapy when the serum T3 levels were less than 80 ng/dl, the rate of ovulation induced by clomiphene increased in parallel with the augmentation of serum T3 levels. This suggests that an adequate circulating level of thyroid hormone is one of the factors responsible for successful induction of ovulation by clomiphene citrate. Furthermore, the short luteal phase and insufficient progesterone secretion observed in patients with subclinical hypothyroxinemia were not improved by clomiphene therapy alone, but were improved markedly by combined treatment with thyroid hormone replacement and clomiphene citrate. These data imply that concomitant clomiphene treatment with thyroid hormone replacement therapy is of a great value not only for ovulation induction, but also for the treatment of luteal-phase defect in patients with subclinical hypothyroxinemia.

Adolescent↗

Gestational age-dependent dual action of epidermal growth factor on human placenta early in gestation.

In order to better understand the role of epidermal growth factor (EGF) in the regulation of placental growth and function, effects of EGF on proliferative activity and differentiated function of trophoblast were examined. Explants from very early (4-5 week) placentas and early (6-7 week, 8-9 week, 10-12 week) placentas were respectively cultured under a serum-free condition in the absence or presence of EGF (100 micrograms/L) for the first 48 h, and the cultures were continued for subsequent 72 h without EGF. The proliferative potential and differentiated function of trophoblast were assessed by immunohistochemical Ki-67 staining and by determining the ability to secrete human CG (hCG) and human placental lactogen (hPL), respectively. Quantitative estimates of proliferative activity based on mean percentage of Ki-67 positive nuclei showed that EGF stimulated proliferative potential of cytotrophoblast in very early (4-5 week) placental explants. The EGF stimulation of trophoblast proliferation was apparent at a 12-h EGF-treated period. By contrast, early (6-12 week) placental explants did not respond to EGF with increase in trophoblast proliferation. Instead, in early placental explant culture EGF stimulated hCG and hPL secretion with a lag period of 72 h, whereas very early placental explants did not respond to EGF with increase in hCG and hPL secretion. These results suggest that EGF exerts gestational age-dependent dual action on the first-trimester placenta: one is to stimulate trophoblast proliferation in 4-5 week placenta and the other is to stimulate differentiated trophoblast function in 6-12 week placenta.

Cell Division↗

The role of maternal thyroid hormones in maintaining early pregnancy in threatened abortion.

To evaluate a possible role of thyroid hormones in maintaining early pregnancy, serum levels of thyroid hormones, TSH and thyroxine-binding globulin (TBG) in 32 patients with a clinical diagnosis of threatened abortion were compared between two groups of patients with favorable and unfavorable pregnancy outcome. Serum levels of T4, T3, free T4 and free T3 levels determined at the onset of clinical signs of threatened abortion were found to be significantly lower in patients (N = 11) who subsequently aborted compared to patients (N = 21) who did not. Serum TSH levels did not differ between the two groups. Serum TBG levels in the patients who subsequently aborted were lower compared to patients with favorable pregnancy outcome. Furthermore, serum levels of T4 and T3 at the onset of threatened abortion in patients who subsequently did not abort were significantly higher compared to levels before pregnancy, whereas little increase in serum T4 and T3 levels relative to the pregnant levels was observed at the onset of clinical signs in the patients who subsequently aborted. These data imply a possible role of thyroid hormones in maintaining early pregnancy, and suggest that maternal serum level of thyroid hormone may be one of the endocrine factors responsible for the outcome of threatened abortion.

Abortion, Threatened↗