Biomedical subjects

H Kurachi

Publications and source records attributed to H Kurachi.

At least 73 records · Page 4Linked to original sources

PubMed1995

Changes in epidermal growth factor receptor and the levels of its ligands during menstrual cycle in human endometrium.

We examined menstrual cycle-dependent changes in the expression of human endometrial epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and epidermal growth factor receptor (EGFR) and their mRNA using immunoblot analysis, 125I-EGF binding, and competitive reverse transcription and polymerase chain reaction (RT-PCR). We also studied their localization in the endometrial tissue by immunohistochemistry. Endometrial samples were obtained at three stages of menstruation: the early follicular stage, which exhibits low serum estradiol (E2) and progesterone (P) levels; the late follicular stage, which exhibits high E2 and low P levels; and the luteal stage, which exhibits high E2 and P levels. Immunohistochemical examination showed that EGF, TGF alpha, and EGFR were localized to the endometrial epithelium. Immunoblot analysis revealed that endometrial EGF, TGF alpha, and EGFR levels were significantly (p < 0.01) increased at the late follicular and luteal stages compared to the early follicular stage. 125I-EGF-specific binding levels at the late follicular and luteal stages were significantly (p < 0.01) higher than at the early follicular stage, consistent with the results of immunoblot analysis. Competitive RT-PCR revealed that EGF, TGF alpha, and EGFR mRNA levels were significantly (p < 0.01) higher at the late follicular and luteal stages than at the early follicular stage. Changes in EGF, TGF alpha, and EGFR mRNA levels were consistent with changes in protein levels. These findings suggest that synthesis and expression of human endometrial EGF, TGF alpha, and EGFR vary with the stage of the menstrual cycle and that their expression in the human endometrium is associated with the increase in the serum E2 but not with the increase in P levels.

Binding, Competitive↗

PubMed1995

Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer.

The aim of this study was to investigate whether mouse placenta produces mature mouse GHRF (mGHRF) and whether cytokines regulate placental mGHRF production. Using Sephadex G-50 gel filtration chromatography and reverse phase HPLC, we identified immunoreactive mGHRF in acid-ethanol extract of placental tissues, which had chromatographic characteristics identical to those of hypothalamic mature mGHRF peptide. The major peak of immunoreactive GHRF in the medium from cultured placental cells was resolved by HPLC at a fraction identical to hypothalamic mature mGHRF. Interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin-M, which all use gp130 as a signal transducer, significantly inhibited mGHRF secretion by cultured placental cells. However, IL-1 alpha and tumor necrosis factor-alpha had no effect on mGHRF secretion. Antibodies to IL-6 or IL-6 receptor completely blocked the inhibitory effect of IL-6 on mGHRF secretion. Anti-LIF, and oncostatin-M inhibited the expression of mGHRF messenger RNA. These results suggest that mouse placenta produces and releases the mature mGHRF, which is indistinguishable by chromatographic criteria from that produced by the hypothalamus, and that signals through gp130 lead to the inhibition of mGHRF production and release in the mouse placenta.

Animals↗

PubMed1995

Estrogen induces epidermal growth factor (EGF) receptor and its ligands in human fallopian tube: involvement of EGF but not transforming growth factor-alpha in estrogen-induced tubal cell growth in vitro.

We studied the estrogen-dependent expression of epidermal growth factor (EGF), transforming growth factor (TGF) alpha, and EGF receptor gene transcripts in human fallopian tubes in vivo and in vitro. Competitive polymerase chain reaction (PCR) was performed on the fallopian tube RNA samples from the postmenopausal women with or without estrogen replacement. Amounts of EGF, TGF alpha, and EGF receptors gene transcripts in the estrogen-treated group (n = 3) were significantly (P < 0.01) more than those in the untreated group (n = 3). Competitive PCR also showed that EGF, TGF alpha, and EGF receptor gene transcripts level in tubal cells were increased by estrogen in vitro: messenger RNA levels of these factors were significantly (P < 0.01, n = 3) increased in cells incubated with 10(-8) M estrogen compared with those in cells without estrogen treatment. We studied whether EGF and/or TGF alpha is involved in the estrogen-induced tubal cell growth in vitro. Estrogen enhanced the [3H]-thymidine incorporation into the cell in dose- and time-dependent manners in culture: estrogen treatment for more than 12 h significantly (P < 0.05) enhanced the [3H]-thymidine incorporation into the cell at 10(-8) M. The estrogen-induced cell growth was observed in association with the increase in EGF, TGF alpha, and EGF receptor messenger RNA levels by estrogen. If the EGF and/or TGF alpha is involved in the cell growth, then the estrogen-induced cell growth should be suppressed by blocking the action of EGF and/or TGF alpha. Therefore, we examined the effects of neutralizing monoclonal antibodies against EGF, TGF alpha, and EGF receptors. Anti-EGF antibody significantly reduced the estrogen-induced increase in [3H]-thymidine incorporation, whereas anti-TGF alpha antibody failed to show the effect. Anti-EGF receptor antibody showed a significant suppressive effect on the estrogen-induced increase in [3H]-thymidine incorporation. Moreover, the growth inhibitory effect by 1 microgram/ml anti-EGF was restored by 10(-8) M EGF but not by TGF alpha even at 10(-6) M. All these data suggest that estrogen induces EGF and TGF alpha/EGF receptors in the human fallopian tube and that EGF but not TGF alpha may be involved in the estrogen-induced human tubal cell growth in vitro.

Antibodies, Monoclonal↗

PubMed1995

Expression of messenger ribonucleic acid for epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha), and EGF receptor in human amnion cells: possible role of TGF alpha in prostaglandin E2 synthesis and cell proliferation.

The amnion plays important structural and functional roles in the maintenance of pregnancy and the initiation of parturition. Recently, we reported that epidermal growth factor (EGF) activates prostaglandin (PG) production and cell growth in cultured amnion cells. In this study, we showed the expression of EGF, transforming growth factor-alpha (TGF alpha), and EGF receptor protein and messenger ribonucleic acid in amnion cells, using an immunofluorescence technique and the reverse transcription-polymerase chain reaction. Next, we studied the effect of TGF alpha on intracellular Ca2+ mobilization and PGE2 production in amnion cells. TGF alpha induced an increase in the intracellular Ca2+ concentration in amnion cells, and this increase was significantly reduced when the cells were incubated with cobalt chloride (a Ca2+ channel blocker; 2.5 mmol/L) or EGTA (a Ca2+ chelator; 5 mmol/L). TGF alpha enhanced PGE2 production, and this increase was significantly inhibited when the cells were incubated with indomethacin (a cyclooxygenase inhibitor; 10 mumol/L), cobalt chloride (2.5 mmol/L), or EGTA (5 mmol/L). We also investigated the effect of TGF alpha on the growth of cultured human amnion cells by using flow cytometric analysis of the DNA content. TGF alpha induced DNA synthesis by human amnion cells, and indomethacin inhibited the TGF alpha-induced DNA synthesis. These results suggest that 1) EGF/TGF alpha are expressed and produced in amnion cells; 2) these endogenous factors may regulate the proliferation of amnion cells in an autocrine or paracrine manner; and 3) these growth factors may exert their effects via intracellular Ca2+ mobilization and PGE2 production.

Amnion↗

PubMed1995

Increase in human placental glucose transporter-1 during pregnancy.

Glucose transporter-1 (GLUT1) has been found in high abundance in human placentas. The purpose of this study was to analyze the changes in the level of GLUT1 during pregnancy. We have analyzed the gestational changes in human placental GLUT1 by [3H]cytochalasin B binding assay, immunoblot analysis and Northern blot analysis. Levels of [3H]cytochalasin B binding to placental membrane in pregnancy at 7-10, 18-20 and 38-40 weeks were 4.2 +/- 0.47, 5.2 +/- 0.46 and 7.2 +/- 0.40 (mean +/- SEM, N = 4) mumol/kg protein, respectively. Amounts of 49-kD and 60-kD proteins detected in immunoblot analysis increased during pregnancy in parallel with [3H]cytochalasin B binding to placental membrane. The GLUT1 mRNA levels also increased during pregnancy. Immunohistochemical examination showed that GLUT1 was localized in the plasma membranes of trophoblast cells. These findings showed that the GLUT1 level increased during pregnancy in human placentas and suggest that GLUT1 may play an important role in fetal development.

Blotting, Northern↗

PubMed1995

Involvement of epidermal growth factor in inducing adiposity of age female mice.

Aged mice exhibit an increase in their body weight (BW), which is associated with fat deposit increase. Epidermal growth factor (EGF) concentration in the submandibular gland also increases with aging. We examined the effects of elevated EGF on the adiposity of aged female mice. Studies were started in two groups of animals consisting of sham-operated (n = 10) and sialoadenectomized (n = 10, Sx; surgical removal of the submandibular glands) mice at 8 weeks of age. Body weight gain and food intake were measured throughout 78 weeks of age in these two groups. Body weight was significantly less in the Sx group throughout 78 weeks, while food intake was not changed by Sx after 12 weeks of age. To examine further if EGF plays a role in the induction of adiposity in aged female mice, sham-operated animals were given 100 microliters anti-EGF rabbit antiserum (anti-EGF group, n = 5) or normal rabbit serum (control group, n = 5) every 3 days, and Sx animals were given 5 micrograms/day EGF (Sx+EGF group, n = 5) or saline (Sx group, n = 5) from 78 weeks of age for 3 weeks. At 81 weeks of age, all animals of these four groups were killed, and carcass fat deposition and fat cell sizes were measured. Although the relative weights (weight ratio to BW) of the liver and kidney were not changed by Sx and anti-EGF treatment, the relative weights of mesenteric and subcutaneous fat tissues and adipocyte weights were significantly decreased in Sx and anti-EGF groups compared with the control group. Moreover, both acyl-CoA synthetase (ACS) and lipoprotein lipase (LPL) mRNA levels were significantly decreased by Sx or anti-EGF administration in mesenteric and subcutaneous fat tissues. On the other hand, EGF administration to Sx animals had no effect on BW, fat tissues and adipocyte weights, and ACS and LPL mRNA levels. The results, however, were consistent with the fact that adipose tissue EGF receptors were down regulated in Sx mice. These findings suggest that EGF may play a role in the induction of adiposity in aged female mice.

Adipose Tissue↗

PubMed1995

Menstrual cycle specific expression of epidermal growth factor receptors in human fallopian tube epithelium.

We studied the expression of epidermal growth factor (EGF) receptor protein and messenger RNA (mRNA) in human fallopian tubes at three stages of the menstrual cycle: early follicular (n = 3), late follicular (n = 3) and luteal (n = 3). Immunohistochemical studies in the ampullary portion of the tubes showed that specific staining was localized to the epithelium and the vascular endothelium. Staining of the epithelium was intense at the late follicular and luteal stages, while it was weak at the early follicular stage. 125I-EGF binding study in the tubal plasma membranes revealed a class of high-affinity EGF receptors. Although dissociation constants were similar between the stages, numbers of binding sites at the late follicular and luteal stages were significantly (P < 0.01) greater than those at the early follicular stage. Western blotting showed that tubal plasma membranes contain M(r) 170,000 EGF receptor protein. The amounts were significantly (P < 0.01, n = 3) greater at the late follicular and luteal stages than those at the early follicular stage. Reverse transcription and polymerase chain reaction (RT-PCR) revealed that EGF receptor mRNA was expressed in all the 9 RNA samples (n = 3 for each stage) from the tubal ampullary portion. The amounts were significantly (P < 0.01, n = 3) greater at the late follicular and luteal stages than those at the early follicular stage (by a competitive PCR). Increase in the amounts of EGF receptor protein and mRNA occurred in association with an increase in serum oestradiol but not progesterone levels. Next we examined whether EGF receptor and its ligands (EGF and transforming growth factor alpha) are directly induced by oestrogen. We found that specific staining for EGF receptor and its ligands in the tubal epithelium was detected (by immunohistochemistry) in postmenopausal women with oestrogen replacement (n = 3), but not in subjects without oestrogen replacement (n = 3). These results suggested that EGF receptors in the human tubal epithelium are expressed in relation to specific stages of the menstrual cycle and that the expression may be induced by oestrogen.

Base Sequence↗

PubMed1995

A case of nonmetastatic trophoblastic disease followed by magnetic resonance imaging.

The consecutive findings of the magnetic resonance (MR) imaging in a patient with nonmetastatic trophoblastic disease are reported. On MR image, there are noted two kinds of MR findings which suggest the existence of trophoblastic disease; one was a typical hypervascular mass of heterogeneous signal intensity within myometrium, and the other was the increase in myometrial and parametrial flow void. The former finding appeared only for a short period while the disease was highly active. The latter finding well paralleled the serum human chorionic gonadotropin (hCG) level, and the remarkable flow void, indicating dilatated blood vessels, disappeared with the complete remission of the disease. These findings suggest that MR imaging may be useful for diagnosing and following gestational trophoblastic disease.

Adult↗

PubMed1995

Cervical invasion of endometrial carcinoma--evaluation by parasagittal MR imaging.

Twenty-seven consecutive patients were examined by T2-(1,800/70 ms) and postcontrast T1-weighted (600/15) spin echo (SE) or dynamic (200/15) SE MR imaging to determine the usefulness of parasagittal MR imaging in assessing cervical invasion of endometrial carcinoma. The images were obtained in a direction parallel to the longitudinal axis of the uterus (parasagittal). The cervical epithelium, being hyperintense on the late phase dynamic and postcontrast T1-weighted SE images, had disappeared partially or totally in all 4 patients with cervical invasion. The enhanced cervical epithelium was completely seen in one patient with the tumor protruding into the cervical canal in a polyp-like form without cervical epithelial invasion. The same was also seen in the 22 patients with the tumor remaining in the corpus cavity. The enhanced parasagittal MR images facilitated the evaluation of the extent of the endometrial carcinoma.

Adenocarcinoma↗

PubMed1994

Decidua is a possible source of serum mouse soluble interleukin-6 receptor (msIL-6R): gestational profile of serum msIL-6R concentration.

The serum concentration of msIL-6R of 10 weeks old virgin ICR mouse assessed by a RIA was 45.6 +/- 6.6 ng/ml. The serum msIL-6R concentration of the pregnant mouse mated at 10 weeks of age was 41.2 +/- 3.0 ng/ml on day 7 of pregnancy. The serum concentration gradually increased during gestation and reached peak on day 17 of pregnancy (149.1 +/- 13.7 ng/ml). On the third day of the puerperium, the serum msIL-6R concentration of the mother from which the pups had been removed on the day of delivery was decreased to the level of that on day 7 of pregnancy. IL-6R mRNA level in the decidua significantly increased during mid and late gestational stages. msIL-6R was detected in the medium of cultured decidual cells (8.03 +/- 0.28 ng/ml), but not placental cells. Western analysis for msIL-6R using the conditioned medium of the cultured decidual cells resulted in a single band at approximately 45 K. To find out a biological role of msIL-6R during gestation, placental cells were incubated with mIL-6 and msIL-6R, and mPL-I concentration in the medium was assessed by RIA. 2.5 nM mIL-6 did not affect the secretion of mPL-I in placental cells; however, addition of msIL-6R resulted in a significant stimulation of mPL-I secretion. These results suggest that serum msIL-6R, which is likely to be secreted from decidua, may play an important role during gestation.

Analysis of Variance↗

PubMed1994

Implantation and growth of epidermal growth factor (EGF) receptor expressing human ovarian cancer xenografts in nude mice is dependent on EGF.

BACKGROUND: The importance of epidermal growth factor (EGF) receptor-dependent growth has not been clarified for in vivo growth of primary human ovarian cancers. METHODS: Seventeen primary human ovarian cancer tissue samples were examined for the presence of EGF receptors by a 125I-EGF-binding study. Three groups of mice were inoculated with EGF receptor expressing and not-expressing cancer tissues. The groups were as follows: control group, Sx group (mice that underwent sialoadenectomy; EGF depleted mice), and Sx+EGF (EGF-replaced) group. The ability of the inoculated tissues to implant and grow then was studied. RESULTS: Of the 17 primary ovarian cancers, 12 expressed EGF receptors and 5 did not. Eight of 12 EGF-receptor expressing cancer tissues implanted and formed growing tumors in control animals. None implanted in the Sx animals. Epidermal growth factor receptor-expressing cancers implanted in Sx animals that received EGF administration. Two of five EGF receptor-negative ovarian cancers implanted and grew in both control and Sx animals. CONCLUSION: Growth of EGF receptor-expressing primary human ovarian cancers may be dependent on EGF in vivo.

Animals↗

PubMed1994

Tumor necrosis factor-alpha (TNF-alpha) inhibits expression of mouse placental lactogen-II through TNF-alpha type-I but not type-II receptor.

The aim of this study was to determine whether TNF-alpha inhibits mPL-II secretion through TNF-RI or TNF-RII, and to investigate the gestational profile of TNF-RI and TNF-RII gene expression. The mouse trophoblast cells from day 12 pregnancy were cultured with or without agonistic polyclonal antibodies directed against the individual TNF-alpha receptors, and mPL-II secretion in the medium was assessed by RIA. Anti-TNF-RI antibody significantly inhibited the mPL-II secretion in a dose- and time-dependent manner, but anti-TNF-RII antibody did not. Moreover, the TNF-RII antibody did not influence the inhibitory effect of the TNF-RI antibody on mPL-II secretion. TNF-RI antibody inhibited the mPL-II gene expression by Northern blot analysis. Amount of the gene expression of TNF-RI in the second half of pregnancy was higher than those in the first half of pregnancy both in vitro and in vivo, although the gene expression of TNF-RII was not detectable by Northern blot analysis using poly(A)+RNA. These results suggest that TNF-RI is a main receptor for TNF-alpha in mouse placenta and that TNF-alpha may have an important role in regulating mPL-II secretion after midpregnancy.

Animals↗

PubMed1994

The hypothalamic-pituitary-ovarian axis in patients with endometriosis is suppressed by leuprolide acetate but not by danazol.

OBJECTIVE: To investigate the effects of leuprolide acetate (LA), a GnRH agonist (GnRH-a), and of danazol on the hypothalamic-pituitary-ovarian axis in patients with endometriosis. DESIGN: Ten patients were divided into LA and danazol treatment groups. MEASURES: Serum levels of E2, immunoreactive and bioactive LH, pulsatility of LH, and gonadotropins release by GnRH. Changes in serum E2 levels by hMG administration during LA treatment. RESULTS: Serum E2 level decreased to near castrated levels during the LA treatment, while it remained unchanged during the danazol treatment. Leuprolide acetate administration resulted in a significant suppression of the serum level of bioactive LH, of the pulsatility of LH release, of the pituitary response to GnRH injection, and of the elevation in the serum E2 level by hMG administration, but danazol treatment did not show these suppressive effects. CONCLUSION: Our results suggest that the hormonal actions of LA and danazol on endometriosis are different from each other, especially in the suppression of serum E2 level.

Adult↗

PubMed1994

Roles of prostaglandins and intracellular free calcium mobilisation in epidermal growth factor-induced proliferation of human amnion cells.

OBJECTIVE: To investigate the mechanisms which regulate the growth of human amnion cells. DESIGN: A prospective descriptive study. SUBJECTS: Women undergoing caesarean section at term before the onset of labour. INTERVENTIONS: Amnion cells were cultured in monolayer. MAIN OUTCOME MEASURES: Cell cycle analysis, intracellular calcium levels, prostaglandin (PG) production rates. RESULTS: Epidermal growth factor (EGF) stimulated intracellular Ca2+ mobilisation and PGE2 production in cultured amnion cells. The addition of a Ca2+ channel blocker (cobalt) or a Ca2+ chelator (EGTA) into the culture medium inhibited intracellular Ca2+ mobilisation and PGE2 production induced by EGF. The analysis of cell cycles showed that EGF induced the initiation of DNA synthesis and that the addition of cobalt or EGTA into the culture medium inhibited EGF-induced DNA synthesis. The addition of a cyclo-oxygenase inhibitor (indomethacin) inhibited PGE2 production and DNA synthesis induced by EGF without the effect on intracellular Ca2+ mobilisation. Moreover, the inhibitory effect of indomethacin on EGF-induced DNA synthesis was attenuated by the addition of exogenous PGE2 or PGF2 alpha. CONCLUSIONS: These data suggest that EGF induces an increase in intracellular Ca2+ levels and the rate of prostaglandin production which leads to proliferation of human amnion cells.

Amnion↗

PubMed1994

Expression of epidermal growth factor and transforming growth factor-alpha in fallopian tube epithelium and their role in embryogenesis.

We studied the expression of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha in human fallopian tube epithelium at various menstrual stages. Immunohistochemical staining using anti-EGF and anti-TGF-alpha antibodies showed a specific staining in ampullary tube epithelium at late follicular and luteal stages but the staining was very weak at the early follicular stage. Quantitative reverse transcription and polymerase chain reaction (RT-PCR) using beta-actin mRNA as an internal standard revealed the menstrual-stage-specific expression of EGF and TGF-alpha gene transcripts: amounts of EGF and TGF-alpha mRNA relative to those of beta-actin were significantly higher at late follicular and luteal stages than at the early follicular stage. To clarify the biological role of these growth factors, mouse 2-cell embryos were cocultured with human fallopian tube epithelial cells with or without blocking the action of these growth factors. Cocultures significantly promoted blastocyst formation, but this promotive effect of the tubal epithelial cells was completely abolished by the addition of anti-EGF and/or anti-TGF-alpha monoclonal neutralizing antibodies to the coculture system. These results demonstrated that EGF and TGF-alpha were synthesized and expressed in fallopian tube epithelium at specific menstrual stages, and may be involved in early embryonic development.

Animals↗

PubMed1994

Epidermal growth factor promotes adipogenesis of 3T3-L1 cell in vitro.

We have reported the importance of epidermal growth factor (EGF) for the induction of obesity in mice. In this study, we studied the effects of EGF on the induction of lipogenic enzymes and on the accumulation of triglyceride in a differentiated mouse adipocyte cell in vitro. Mouse 3T3-L1 preadipocytic cells differentiated into mature adipocytes after the differentiation procedure by insulin, dexamethasone, and methyl-isobutyl-xanthine. 125I-EGF binding studies in the differentiated 3T3-L1 cells showed specific 125I-EGF bindings, and they expressed gene transcripts for EGF receptors by reverse transcription and polymerase chain reaction at all differentiative stages examined. Although EGF showed inhibitory effects on the triglyceride accumulation when administered to the preadipocytic 3T3-L1 cells, EGF enhanced the adipogenesis in the differentiated cells in dose- and time-dependent manners. Administration of EGF at 0.1-1 nM from 4 days after the differentiation procedure for 10 days, significantly enhanced the acyl-Co A synthetase and lipoprotein lipase messenger RNA levels, both of which are rate-limiting enzymes to synthesize triglyceride in adipocytes. Moreover, 0.1-1 nM EGF increased the amounts of triglyceride accumulated in the cells, in proportion to the acyl-Co A synthetase and lipoprotein lipase messenger RNA levels. EGF rather failed the adipogenesis at 10 nM. Time course studies revealed that 1 nM EGF significantly increased the intracellular triglyceride levels from 4 through 16 days administration. These results suggest that EGF shows biphasic effects on adipocytes: although EGF inhibits preadipocytes differentiation into mature adipocytes, it promotes adipogenesis in the differentiated adipocytes.

3T3 Cells↗

PubMed1994

Identification of estrogen receptor in human adipose tissue and adipocytes.

Estrogen has various effects on adipose tissue. Although the presence of estrogen receptor (ER) has been demonstrated in rat adipose tissue and adipocytes, ER has not been identified in human adipose tissue. In this study, we demonstrated the existence of ER protein and ER messenger RNA (mRNA) in human sc adipose tissue and adipocytes. The cytosol fraction of human adipose tissue was partially purified by ammonium sulfate precipitation, and the presence of ER protein was analyzed by [3H]estradiol (E2) binding assay and Western blot analysis. [3H]E2 binding assay showed a low specific binding due to high nonspecific binding, and the dissociation constant (Kd) and maximal binding sites could not be obtained by Scatchard analysis. Western blots, however, showed the presence of ER protein in both the partially purified cytosol and nuclear fractions of human adipose tissue. The mol wt of ER in both fractions was approximately 66,000. Furthermore, Northern blot analysis of total RNA samples isolated from human adipose tissue showed the expression of ER mRNA at 6.2 kilobase in size. ER mRNA was also identified in isolated human adipocytes by the reverse transcription and polymerase chain reaction. These results indicated that both ER protein and ER mRNA are expressed in human adipocytes, suggesting that the effect of estrogen on human adipose tissues might involve a direct action.

Adipocytes↗

PubMed1994

Involvement of autocrine mechanism of transforming growth factor-beta in the functional differentiation of pregnant mouse mammary gland.

We studied the presence and possible role of the autocrine mechanism of transforming growth factor-beta (TGF-beta) in pregnant mouse mammary gland. Northern blot analysis revealed the expression of the TGF-beta 1 gene transcript at 2.5 kb in mammary epithelial cells isolated from virgin and mid-pregnant mice. The TGF-beta activity was higher in the conditioned medium from mid-pregnant mouse mammary explants than that from virgin explants by a bioassay system using mink lung epithelial cells. A binding study using [125I]TGF-beta 1 as a ligand showed that pregnant mouse mammary epithelial cells possessed a single class of high-affinity TGF-beta 1 binding sites (Kd = 28.0 pmol/l, 1.2 x 10(4) sites per cell). These results suggested the presence of a TGF-beta autocrine mechanism in pregnant mouse mammary epithelial cells. Next, we examined the effect of TGF-beta 1 on the functional differentiation of pregnant mouse mammary gland. Transforming growth factor-beta 1 inhibited alpha-lactalbumin production in cultured mammary explants from mid-pregnant mice in a dose-dependent manner without inhibiting DNA synthesis. All these results suggest that TGF-beta may play a role in regulating the functional differentiation of mouse mammary glands during pregnancy.

Animals↗