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Biomedical subjects

H Kurachi

Publications and source records attributed to H Kurachi.

At least 109 records · Page 6Linked to original sources

Decrease in epidermal growth factor receptor and its messenger ribonucleic acid levels in intrauterine growth-retarded and diabetes mellitus-complicated pregnancies.

We measured the amounts of epidermal growth factor receptor (EGFR) in plasma membranes from human placentas at term delivery in three groups: appropriate for gestational age (AGA), intrauterine growth-retarded (IUGR), and diabetes mellitus-complicated (DM) pregnancies. At the same time, EGFR mRNA levels were examined in three groups by dot and Northern blot analyses. Binding studies were performed using 125I-labeled human EGF as a ligand, and two classes (high and low) of binding sites were found in all specimens. Although dissociation constants (Kd) were not significantly different among three groups, the number of binding sites was significantly decreased in IUGR and DM placentas compared to that in the AGA group. Total cellular RNA was isolated from a part of the placentas used for binding studies using the guanidinium CsCl method, denatured, and dot blotted onto nitrocellulose filter. Poly(A)+ RNA was selected from the total RNA, electrophoresed in 1% agarose gel, and transferred onto nitrocellulose filters. Then, hybridization with 32P-labeled pE7 (a cDNA of EGFR), autoradiography, and densitometry were performed. The amounts of mRNA hybridized with pE7 were reduced in IUGR and DM placentas compared to that in the AGA group. The molecular sizes of EGFR mRNA were 10 and 5.6 kilobases in all three groups. These results suggest possible physiological actions of EGF on adequate feto-placental growth and development in human pregnancy.

Diabetes Mellitus↗

Changes of bioactive luteinizing hormone after laparoscopic ovarian cautery in patients with polycystic ovarian syndrome.

The serum levels of bioactive luteinizing hormone (LH), immunoreactive LH, follicle-stimulating hormone, androstenedione (A), and testosterone (T) were determined in nine anovulatory women with polycystic ovarian syndrome (PCOS) before and after laparoscopic ovarian cautery. Eight ovulated spontaneously and three conceived after treatment. Before treatment, the mean (+/- SEM) levels of bioactive LH, immunoreactive LH, A, and T were 51.4 +/- 8.6 mIU/mL, 36.0 +/- 4.5 mIU/mL, 1.98 +/- 0.35 ng/mL, and 1.18 +/- 0.13 ng/mL, respectively, which were significantly higher than those of five control women (19.2 +/- 1.6 mIU/mL, 21.4 +/- 1.2 mIU/mL, 0.54 +/- 0.03 ng/mL, 0.28 +/- 0.03 ng/mL). After treatment, the mean levels of these hormones had significantly decreased. Decreases in the levels of these hormones by laparoscopic ovarian cautery in women with PCOS may result in both restoration of the ovulatory cycle and achievement of pregnancy.

Adult↗

Electrocautery in polycystic ovary syndrome.

The serum levels of bioactive luteinizing hormone (LH), immunoreactive LH, follicle-stimulating hormone (FSH), and testosterone were determined in eleven anovulatory women with polycystic ovary syndrome (PCOS) before and after laparoscopic ovarian cautery. Before treatment, the mean +/- SEM levels of bioactive and immunoreactive LH and testosterone were 53.1 +/- 7.9 mIU/ml, 35.2 +/- 3.9 mIU/ml, and 1.14 +/- 0.13 ng/ml, respectively, which were significantly higher than those of five control women (19.2 +/- 1.6 mIU/ml, 21.4 +/- 1.2 mIU/ml, 0.28 +/- 0.03 ng/ml). After treatment, the mean levels of these hormones decreased significantly, ten women ovulated spontaneously and four conceived. The present results suggests that decreases in the levels of these hormones by laparoscopic ovarian cautery in women with PCOS may result in both restoration of the ovulatory cycle and the achievement of pregnancy.

Adult↗

Suppression of serum immunoreactive human epidermal growth factor by acute increase in prolactin in women.

Epidermal growth factor (EGF) is known to stimulate proliferation of various mammalian cells and secretion of prolactin (PRL) from rat anterior pituitary tumor cells. The effect of an acute increase in serum PRL induced by thyrotropin releasing hormone (TRH) or metoclopramide (MCP) on the serum immunoreactive EGF concentration was examined in nine hyperprolactinemic patients and eight normoprolactinemic women. The basal level of serum EGF in normoprolactinemic subjects was 472.8 +/- 51.1 pg/ml (Mean +/- SEM), which was not significantly different from that in hyperprolactinemic patients (487.8 +/- 22.5 pg/ml). The serum EGF concentration was decreased to 40-50% of the basal level after the abrupt increase in serum PRL induced by the injection of TRH or MCP in normoprolactinemic subjects, but no significant change in serum EGF occurred in hyperprolactinemic patients after MCP injection, in spite of a significant increase in PRL. These results suggest that an acute increase of serum PRL in normoprolactinemic women, but not in hyperprolactinemic patients, suppresses serum EGF.

Adenoma↗

Second pregnancy with spontaneous ovulation following clomiphene- or gonadotropin-induced pregnancy.

For investigation of the rates of spontaneous pregnancy following termination of pregnancy induced by treatment with clomiphene or human menopausal gonadotropin-human chorionic gonadotropin (hMG-hCG) and of spontaneous abortion in the second pregnancy, 119 women (58 with an anovulatory cycle and 141 with amenorrhea) who desired another pregnancy were studied. The rate of spontaneous pregnancy following pregnancy induced by clomiphene was 46.6%, which was significantly (p less than 0.001) higher than that following pregnancy induced by hMG (14.9%). The mean (+/- SEM) period between the termination of the first induced-ovulation pregnancy and the second spontaneous pregnancy was 16.6 +/- 1.4 months. The spontaneous abortion rates in the second pregnancies after pregnancies induced by clomiphene and hMG were 7.5% and 9.8%, respectively, which were significantly (p less than 0.001, p less than 0.05) lower than those in the first pregnancy (25.7%, 33.0%). There was no difference between the spontaneous abortion rates following a first pregnancy which terminated in abortion and those following a pregnancy which ended in birth. These data suggest that a first pregnancy in anovulatory women may restore the ovulatory cycle and have a beneficial effect on the rates of spontaneous abortion in the second pregnancy.

Clomiphene↗

Changes in epidermal growth factor receptor and its messenger ribonucleic acid levels in human placenta and isolated trophoblast cells during pregnancy.

We measured the amounts of epidermal growth factor receptor (EGFR) in plasma membrane fractions purified from early, middle, and term placentas and from isolated trophoblast cells, and the amounts of EGFR mRNA were measured in whole placentas. Binding studies were performed using [125I] human EGF as ligand; two classes (high and low) of binding sites were found in placental and trophoblast cell plasma membranes. Although dissociation constants (Kd) were not significantly different in placental plasma membranes from the three stages of pregnancy, the number of binding sites increased significantly during pregnancy. The mean numbers of binding sites were 0.72 +/- 0.18 (+/- SE), 1.02 +/- 0.10, and 1.89 +/- 0.21 pmol/mg protein (high affinity sites) in plasma membrane fractions from early, middle, and term whole placentas, respectively. A similar significant increase was found when the membranes were prepared from isolated trophoblast cells. At the same time, total cellular RNA was isolated, denatured, and blotted onto nitrocellulose membranes. Then, hybridization with 32P-labeled pE 7, a cDNA of EGFR, or 32P-labeled v-erb-B oncogene, autoradiography, and densitometry were performed. The EGFR mRNA increased proportionally to the changes in EGFR during pregnancy. These results indicate that EGF-binding sites and EGFR production increase in human placentas throughout the gestational period.

Blotting, Northern↗

Study of the growth factors for the mammary gland: epidermal growth factor and mesenchyme-derived growth factor.

The physiological importance of EGF in the development of the mouse mammary gland during pregnancy and in spontaneous mammary tumorigenesis has been documented by a series of experimental results presented herein. In our study, we have taken a variety of experimental approaches including radioimmunoassay of EGF in the submandibular gland and plasma, mammary gland organ/cell culture, EGF receptor assay, sialoadenectomy and treatment with EGF and EGF antibodies to assess the role of EGF in the mammary gland. In particular, studies employing sialoadenectomy and EGF replacement have provided valuable information concerning the function of EGF in the body. These studies are possible in the mouse system because the submandibular gland serves as a major source of circulating EGF and also because purified mouse EGF is available commercially. Our work on the biological, endocrinological, and physiological aspects of EGF in normal and neoplastic growth of the mammary gland should be useful for the study of the regulation of mammary gland growth at the molecular level as well as for clinical investigations of mammary tumors. Finally, our findings of a mammary growth factor in embryonic mesenchymal cultures suggest the possible involvement of paracrine growth factor(s) in mammary cell growth. Further progress in this area is needed for better understanding of the complex process of mammary gland growth and development.

Animals↗

A physiological role of epidermal growth factor in male reproductive function.

Epidermal growth factor (EGF) stimulates the proliferation of various mammalian cells in culture, but its physiological role is not well defined. In mature male mice, large amounts of EGF are produced in the submandibular gland; it is present in the circulation at approximately 5 nanograms of EGF per milliliter of plasma. Sialoadenectomy (removal of the submandibular glands) decreased the amount of circulating EGF to an undetectable level but did not affect the circulating levels of testosterone or follicle-stimulating hormone. The number of mature sperm in the epididymis decreased by as much as 55 percent; the number of spermatids in the testis decreased by 40 to 50 percent; and the number of spermatocytes increased by about 20 percent. Administration of EGF to sialoadenectomized mice restored both the sperm content of the epididymis and the number of spermatids in the testis to normal. Thus, EGF may play a role in male reproductive function by stimulating the meiotic phase of spermatogenesis.

Animals↗

Regulation of the level of epidermal growth factor by oestrogen in the submandibular gland of female mice.

The concentration of epidermal growth factor (EGF) in the submandibular gland of immature female mice (less than 6 weeks old) was low, ranging from 0.07 to 0.17 pmol (0.4 to 1.0 ng)/mg wet wt, but increasing to 7.61 pmol/mg wet wt by 8 weeks of age. It remained relatively constant up to 24 weeks of age, but thereafter the glandular EGF concentration increased again during the post-reproductive period to reach 62.9 pmol/mg wet wt. In contrast, the glandular EGF content in male mice increased greatly during the first 17 weeks of age to about 310 pmol/mg wet wt, and thereafter remained relatively constant up to 48 weeks of age. Ovariectomy of mature virgin mice markedly increased the glandular concentration of EGF to about 74.4 pmol/mg wet wt 4 weeks after the operation. This increase was suppressed by oestradiol-17 beta administered to ovariectomized mice at a dose of 1 microgram/mouse per day but not by 1 mg progesterone. Histological studies indicated that granular convoluted tubular cells that produced EGF in the submandibular gland were much less abundant in 12-week-old female and in oestrogen-treated ovariectomized mature mice than in 40-week-old female and ovariectomized mature mice. We conclude that oestrogen suppresses the concentration of EGF in the submandibular gland of female mice.

Aging↗

Evidence for the involvement of the submandibular gland epidermal growth factor in mouse mammary tumorigenesis.

The submandibular gland is a rich source of epidermal growth factor (EGF) in mice. The concentration of EGF in the gland of virgin female mice of C3H/HeN strain increased as much as 9-fold from the age of 30 to 52 weeks. During this period, the incidence of mammary tumor in virgin females increased markedly to a maximal level of 62.5% (n = 48) at 52 weeks of age. Removal of the submandibular gland (sialoadenectomy) of virgin mice 14-22 weeks old reduced the tumor incidence to 12.8% (n = 39) at the age of 52 weeks and also increased the latency period of mammary tumor development as much as 14 weeks when compared to that of normal mice. Long-term treatment of sialoadenectomized virgin mice with EGF (5 micrograms per mouse every other day) increased the tumor incidence to 33.3%. Moreover, sialoadenectomy of mammary tumor-bearing animals caused a rapid and sustained cessation of tumor growth, but EGF administration (5 micrograms per mouse per day) quickly restored the rate of tumor growth to a normal level. These results indicate that submandibular gland EGF plays a crucial role in mouse mammary tumorigenesis.

Adenocarcinoma↗

Changes in epidermal growth factor concentrations of submandibular gland, plasma and urine of normal and sialoadenectomized female mice during various reproductive stages.

The concentrations of epidermal growth factor (EGF) were measured by radioimmunoassay in the submandibular gland, plasma and urine of adult female C3H/HeN mice whilst virgin and during pregnancy, lactation and after lactation. During gestation there was a significant increase in the submandibular EGF concentration which was five to seven times higher than that found in virgin mice. The level of EGF in the gland remained high during the period of lactation and even several weeks after lactation. Plasma EGF levels were also increased during the periods of pregnancy, lactation and after lactation when compared with those of virgin mice. These increases were, however, apparent only between 24.00 and 08.00 h, because of circadian variations in circulating EGF. The level of plasma EGF was significantly (P less than 0.05) higher during the 24.00-08.00 h period than during the 12.00-20.00 h period in all stages examined. Concentrations of EGF in the urine of virgin, pregnant, lactating and primiparous mice remained relatively constant, and the levels were much higher than those in the plasma. Similar studies using sialoadenectomized pregnant and lactating mice indicated that the plasma levels of EGF were below the level of sensitivity of the assay (less than 16.5 pmol/l (less than 0.1 ng/ml] even during the 24.00-08.00 h period, whereas urinary EGF remained at high levels which were similar to those of normal pregnant and lactating mice. These results suggest that submandibular EGF contributes to the increase in plasma EGF which occurs after gestation, but is not the major source of the urinary EGF.

Animals↗

Specific antibodies to porcine zona pellucida detected by quantitative radioimmunoassay in both fertile and infertile women.

The specific radioimmunoassay system was developed for the titration of the antibodies to porcine zona pellucida (ZP) in human sera by using 125I-labeled purified porcine ZP as antigen, which is known to have cross-reactivity with human ZP. The antibodies in human sera were detected in 3 of 11 (27%) women with unexplained infertility, in 16 of 48 (33%) amenorrheic patients, in 4 of 12 (33%) fertile women, and in 3 of 10 (30%) men. Moreover, antibody titers in infertile women were no higher than those in fertile women and in men. These results seem to suggest that the antibodies in human sera that cross-react with porcine ZP may not be an important factor in causing infertility in women.

Animals↗

Restoration of the ovarian response to gonadotropins in patients after molar abortion.

The recovery of the ovarian response to gonadotropin stimulation after molar abortion was investigated in relation to the serum human chorionic gonadotropin (hCG) level. Thirteen women with an aborted mole were given 225 IU of human menopausal gonadotropin (hMG) per day for 3 consecutive days, and their serum levels of estradiol (E2) were determined by radioimmunoassay on days 1, 3, 5, and 7 after hMG administration. Women with serum hCG levels of less than 200 mIU/ml exhibited a normal increase in serum E2 levels in response to hMG, whereas women with serum hCG levels of 2000 mIU/ml or more did not show any change after hMG administration. These findings suggest that a serum level of hCG in excess of 2000 mIU/ml prevents normal ovarian E2 responsiveness to exogenous gonadotropin stimulation.

Abortion, Spontaneous↗