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S Handwerger

Publications and source records attributed to S Handwerger.

At least 55 records · Page 3Linked to original sources

Human uterine decidual macrophages express renin.

Human uterine decidual tissue contains many cell types, including stromal cells, fibroblasts, and macrophages. Earlier studies have shown that decidualized uterine stromal cells express renin, primarily in the form of prorenin. However, the possibility that decidual macrophages, which comprise about 30% of the cells in term decidua, also express renin has not been investigated. To determine whether macrophages express renin, macrophages were isolated from enzymatically dispersed term decidual cells using immunomagnetic beads coupled to antibodies to human leukocyte antigen (HLA)-DR, an antigen present on macrophages, but not other decidual cells. The isolated cells were 92.1% CD14 positive and contained the messenger ribonucleic acids (mRNA) for the interleukin-2 type alpha receptor, but not for PRL, a specific marker of decidualized stromal cells. Immunocytochemical studies of the macrophage-enriched fraction demonstrated that the macrophages contained renin, and reverse transcription-polymerase chain reaction analysis with primers specific for renin indicated that the fraction also contained renin mRNA. Renin was detected in the conditioned medium of cultures of the macrophage-enriched preparations, greater than 90% of which was in the form of prorenin. As anticipated, renin and renin mRNA were also detected in the HLA-DR negative cells, more than 80% of which stained with specific antiserum to PRL. Peripheral mononuclear cells also expressed renin mRNA, as determined by reverse transcription-polymerase chain reaction analysis. These results demonstrate that human decidual macrophages express renin and indicate that renin is expressed by several cell types in decidual tissue.

Antibodies↗

Ontogeny of the expression and regulation of interleukin-6 (IL-6) and IL-1 mRNAs by human trophoblast cells during differentiation in vitro.

During human placental differentiation, mononuclear cytotrophoblast cells fuse and differentiate into syncytiotrophoblast cells. Although syncytiotrophoblast cells have been shown to express interleukin-1 alpha (IL-1 alpha), IL-1 beta and IL-6, the pattern of expression of these cytokines during placental differentiation is unknown. We have examined the expression of IL-1 alpha, IL-1 beta and IL-6 mRNA during differentiation of cytotrophoblast cells in culture. IL-1 alpha, IL-1 beta and IL-6 mRNA levels were determined by semiquantitative reverse transcription-PCR analysis using glyceraldehyde phosphate dehydrogenase as an internal control. All three cytokine mRNA levels decreased markedly during trophoblast differentiation. After 6 days in culture, when almost all the cytotrophoblast cells had fused and differentiated into syncytiotrophoblast cells, the amounts of IL-1 alpha, IL-1 beta and IL-6 mRNA were decreased by 87.1, 72.1 and 60.9% respectively. Exogenous IL-6 had differential effects on cytokine mRNA expression. When added to placental cultures during the first 6 days of culture, IL-6 markedly inhibited IL-6, IL-1 alpha and IL-1 beta mRNA expression. However, when added to the cells during days 6-9 of culture, when most of the cells were syncytiotrophoblast cells, IL-6 stimulated IL-1 alpha and IL-1 beta mRNA expression. The results of these studies indicate that IL-1 alpha, IL-1 beta and IL-6 mRNA expression decreases markedly during cytotrophoblast differentiation in vitro and that the regulation of trophoblast cytokine mRNA levels changes during differentiation.

Base Sequence↗

Expression of retinoic acid receptor subtypes and cellular retinoic acid binding protein-II mRNAs during differentiation of human trophoblast cells.

An in vitro model of trophoblast cell differentiation has been used to examine the developmental expression of retinoid receptor mRNAs during the differentiation of human placental cytotrophoblast cells to syncytiotrophoblast cells. The levels of RAR alpha, RAR beta, RXR alpha mRNA increased by 12, 7, and 3 fold, respectively, during trophoblast differentiation, while the levels of RAR gamma mRNA remained relatively constant; and the increase in retinoid receptor mRNA expression preceded the increase in the expression of placental lactogen (hPL), a specific marker of syncytiotrophoblast cells. CRABP-II mRNA levels were lower in cytotrophoblast cells than in syncytiotrophoblast cells. Mobility shift assays demonstrated the appearance of a specific band that bound to a labeled DNA probe containing a retinoic acid responsive element (RARE) that was most intense from nuclear extracts from syncytiotrophoblast cells. These results suggest possible roles for these receptors in the regulation of trophoblast differentiation and hPL gene expression.

Base Sequence↗

Binding studies of vancomycin to the cytoplasmic peptidoglycan precursors by affinity capillary electrophoresis.

The ability of vancomycin to bind three cytoplasmic peptidoglycan precursors in bacterial species was studied using affinity capillary electrophoresis (ACE). The ACE binding assay was established with the normal precursor, UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala, from Staphylococcus aureus 209P under conditions where vancomycin served as substrate ligand included in the buffer system. This precursor was found to bind to vancomycin with a binding constant of 1.6 x 10(-5) M-1 (or a dissociation constant of 62.5 microM) obtained from Scatchard plots. No migration shifting was observed under the same conditions for the other two precursors from Leuconostoc mesenteroides VR1 and Lactobacillus casei 7469, suggesting structural modifications at the stem peptide terminus. The reduction of their affinity to vancomycin is consistent with proposed structures, UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-(L-Ala)-D-Ala-D-lactate and UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate, from L. mesenteroides VR1 and L. casei 7469, respectively, based on mass spectrometry. This rapid technique provides additional evidence in the understanding of one mechanism of bacterial resistance.

Amino Acid Sequence↗

Lipopolysaccharides inhibit prolactin and renin release from human decidual cells.

Human decidual tissue consists of a heterogeneous population of cells, including stromal cells, lymphocytes, and macrophages. Lipopolysaccharides (LPS), which bind to specific cell surface receptors on macrophages, have been shown to increase prostaglandin production by the decidua and amnion. To determine whether LPS may also affect decidual hormone production, we have examined the effects of LPS on the synthesis and release of prolactin and renin. Dispersed cells from term decidual tissue exposed to LPS L2880 (Escherichia coli, 1 microgram/ml) released significantly less prolactin and renin than control cells after 24 h of exposure. Maximal inhibition of prolactin (31.6%) and renin (62.5%) release was noted at 72 and 96 h of exposure, respectively (p < or = 0.0002 in each instance). The inhibition of prolactin and renin release was dose-dependent, with half-maximal inhibition at a dose of approximately 10 ng/ml. LPS caused a decrease in prolactin synthesis as well as release. In addition, LPS inhibited the stimulation of prolactin release in response to insulin, a known secretagogue of prolactin release. After 24, 48, and 72 h of exposure, the magnitude of the stimulation of prolactin release by cells exposed to insulin (100 ng/ml) in the presence of LPS (1 microgram/ml) was 84.5, 57.5, and 35.2% less, respectively, than that of cells exposed to insulin alone (p = 0.0001 in each instance). LPS L6011 (Salmonella endotoxin) also inhibited prolactin and renin release. LPS had no effect on overall protein or DNA synthesis and did not cause release of alkaline phosphatase and lactate dehydrogenase.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival↗

Alterations in peptidoglycan precursors and vancomycin susceptibility in Tn917 insertion mutants of Enterococcus faecalis 221.

Derivatives of the highly vancomycin-resistant Enterococcus faecalis strain 221 (MIC, 1,024 micrograms/ml) harboring Tn917 insertions in vanR, vanH, and vanA were compared with the parent strain and the susceptible plasmid-free strain JH2-2 (MIC, 2 micrograms/ml). Cytoplasmic pools of UDP-N-acetyl-muramyl-peptide precursors of strain 221 contained the depsipeptide-terminating precursor as well as elevated levels of both the tripeptide and tetrapeptide precursors. Insertional inactivation of vanR resulted in the loss of carboxypeptidase activity, full susceptibility to vancomycin, and precursor pools similar to those of JH2-2. For the vanA insertional mutant the MBC of vancomycin was fourfold higher than that for JH2-2, and the mutant had increased levels of tripeptide and tetrapeptide precursors compared with those for JH2-2. The vanH insertional mutant showed elevated levels of these precursors, as well as a small amount of depsipeptide, and both the MIC and the MBC of vancomycin were increased compared with those for JH2-2. These findings suggest that DD-carboxypeptidase activity, under the control of vanR, results in increased pools of both tripeptide and tetrapeptide precursors, which may contribute to survival in the presence of vancomycin.

Amino Acid Sequence↗

Vancomycin-resistant Leuconostoc mesenteroides and Lactobacillus casei synthesize cytoplasmic peptidoglycan precursors that terminate in lactate.

The emergence of acquired high-level resistance among Enterococcus species has renewed interest in mechanisms of resistance to glycopeptide antibiotics in gram-positive bacteria. In Enterococcus faecalis and Enterococcus faecium, resistance is encoded by the van gene cluster and is due to the production of a peptidoglycan precursor terminating in D-alanyl-D-lactate, to which vancomycin does not bind. Most Leuconostoc and many Lactobacillus species are intrinsically resistant to high levels of glycopeptide antibiotics, but the mechanism of resistance has not been elucidated. To determine whether the mechanisms of resistance are similar in intrinsically resistant bacteria, cytoplasmic peptidoglycan precursors were isolated from Leuconostoc mesenteroides and Lactobacillus casei and analyzed by mass spectrometry, revealing structures consistent with UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-(L-Ala)-D-Ala-D-lactate and UDP-N-acetylmuramyl-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate, respectively.

Amino Acid Sequence↗

Endothelin-1 modulates renin and prolactin release from human decidua by different mechanisms.

Endothelin (ET)-1 stimulates the synthesis and release of renin and inhibits the expression of prolactin (PRL) from term human decidual cells. To examine the mechanisms by which ET-1 exerts its differential effects on renin and PRL expression, we have studied total renin and PRL release from term human decidual cells in response to pharmacological agents that affect calcium- and protein kinase C-dependent mechanisms. Calcium ionophore A-23187 stimulated basal renin release and potentiated ET-1-stimulated renin release but had no effect on basal or ET-inhibited PRL release. The calcium channel blocker nifedipine inhibited ET-1-stimulated renin release but had no effect on PRL release. The protein kinase C agonist phorbol 12-myristate 13-acetate (PMA) stimulated basal renin release and potentiated the effect of ET-1 on renin release. However, PMA inhibited basal PRL release and also enhanced the inhibitory effect of ET-1. The PKC inhibitor staurosporine increased basal PRL release and completely reversed the inhibitory effect of ET on PRL release. These results indicate that the effects of ET-1 on both decidual renin and PRL release are dependent on the activation of protein kinase C. However, the effect of ET-1 on renin release appears to be dependent on extracellular calcium, whereas the effect on PRL is not influenced by extracellular calcium.

Alkaloids↗

Prostaglandin E2 enhances human endometrial stromal cell differentiation.

Endometrial stromal differentiation (decidualization) is essential for implantation of the developing blastocyst. Because prostaglandins (PGs) are synthesized in the endometrium, and PG-binding sites have been demonstrated in the proliferative endometrial stromal cell (the precursor of the decidual cell), experiments were performed to determine whether PGs are involved in the process of decidualization. Human endometrial stromal cells were cultured for 18 days in Dulbeco's Modified Eagle's Medium-2% fetal bovine serum with 1 microM medroxyprogesterone acetate (MPA) and 10 nM estradiol, with and without PGE2 or PGF2 alpha. Expression of PRL was used as a marker of decidualization. In the presence of estradiol and MPA alone (control), PRL was detected beginning on day 9 and gradually increased through day 18. In contrast, PRL was detected on day 3 in the PGE2-treated cells, and the magnitude of stimulation in these cells on days 9-12 was 1300-1400% of that in control cells. Furthermore, the PRL mRNA content of the PGE2-treated cells on day 12 was 4.6-fold greater than that in the control cells. The effect of PGE2 on PRL production was dose dependent, with a minimal effective dose of 10(-10) M. PGE2 in the absence of steroids had a minimal effect on PRL production. In contrast to PGE2, PGF2 alpha treatment had no effect on PRL expression in steroid-treated cells. These results indicate that there are synergistic effects among PGE2, estradiol, and MPA, resulting in acceleration of endometrial stromal cell differentiation and enhanced PRL expression.

Carrier Proteins↗

Tumor necrosis factor-alpha inhibits the synthesis and release of human decidual prolactin.

Bone marrow-derived cells are major cellular components of human decidua, with macrophages comprising about 30% of the cells in term tissue. Because cytokines released by bone marrow-derived cells are known to affect hormone release in many tissues, we examined whether cytokines affect the release of PRL from human decidual cells. Exposure of primary decidual cell cultures from term pregnancies to tumor necrosis factor-alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), IL-1 beta, transforming growth factor-beta (TGF beta), and IL-8 caused dose-dependent inhibition of PRL release. Initial inhibition by each of the cytokines was noted after 24 h of exposure, and maximal inhibition of 33-60% occurred after 3 or 4 days. The maximal inhibitions by TNF alpha, IL-1 alpha, IL-1 beta, TGF beta, and IL-8 were 60%, 55%, 46%, 36%, and 33%, respectively, and the half-maximal effective doses of TNF alpha, IL-1 alpha, IL-1 beta, and TGF beta were 70, 2.8, 0.6, and 40 pM, respectively. The cytokine-induced decrease in decidual PRL release was accompanied by a decrease in PRL synthesis. In contrast to the other cytokines, IL-6 had no effect on basal PRL release. TNF alpha, IL-1 alpha, IL-1 beta, and IL-8 also inhibited stimulation of the synthesis and release of PRL and PRL mRNA levels in response to insulin. The effect of the cytokines was not due to inhibition of cell proliferation, because the DNA content of the cells was not affected by cytokine treatment. These results strongly suggest that cytokines released by decidual macrophages and other bone marrow-derived cells may have a paracrine role in the regulation of decidual PRL expression.

Cells, Cultured↗

Human cytotrophoblast cells cultured in maternal serum progress to a differentiated syncytial phenotype expressing both human chorionic gonadotropin and human placental lactogen.

Under appropriate conditions, protease-dispersed cytotrophoblast cells from human term placenta fuse and differentiate into syncytiotrophoblast cells that express hCG. Although human placental lactogen (hPL) is also expressed by the syncytiotrophoblast in vivo, little hPL is expressed by trophoblast cells differentiated in vitro using standard tissue culture medium or keratinocyte growth medium supplemented with fetal bovine serum. In this report, we demonstrate that cytotrophoblast cells fuse and differentiate to a phenotype that expresses large amounts of both hCG and hPL when cultured in medium containing maternal serum. When protease-dispersed cytotrophoblast cells were plated in RPMI-1640 supplemented with 10% second trimester (16-22 week) maternal serum (STMS medium), extensive cell fusion was observed by day 3 in culture. Cell fusion appeared to be essentially complete by day 6, coinciding with the peak of hCG expression and the initiation of hPL expression. The peak of hCG expression occurred between days 4-7 of an experiment; the range for maximal release of hCG was 0.1-3.7 micrograms/24 h.well when cells were plated at a density of 10(6)/well. In contrast, the peak of hPL expression occurred between days 7-11 of an experiment, and the range of maximal hPL release was 0.9-3.5 micrograms/24 h.well. Northern blot analysis indicated that the level of hPL messenger RNA (mRNA) paralleled the release of hormone. However, whereas the hCG beta-subunit mRNA paralleled the release of hCG, the hCG alpha-subunit mRNA did not, suggesting that the two genes are independently regulated. Cells cultured in nonpregnant (male or female) serum-supplemented medium also differentiated to the syncytiotrophoblast phenotype following a temporal pattern almost identical to that observed for cells cultured in STMS. However, the quantity of hormone released was at least 2-fold greater with STMS. Compared to RPMI-1640 or keratinocyte growth medium supplemented with 10% fetal bovine serum, STMS induced equal or greater expression of hCG and substantially greater expression of hPL at the level of both mRNA and protein. The extent of cell fusion, the level of hormone expression, and the regulated patterns of hormone expression suggest that cytotrophoblast cells cultured in maternal serum progress to an advanced stage of trophoblast differentiation.

Blood↗

Interleukin-6 stimulates placental lactogen expression by human trophoblast cells.

Interleukin-6 (IL-6) stimulates the release of hCG from syncytiotrophoblast cells, but the effects of IL-6 and other cytokines on the release of placental lactogen (hPL) are unknown. To determine the effect of IL-6 on hPL release, we exposed an enriched fraction of trophoblast cells (prepared by the isopycnic centrifugation of enzymatically dispersed term placenta) continuously to IL-6 (500 U/ml) for up to 6 days. The amounts of hPL released by the IL-6-exposed cells during days 3 and 6 were 177.6 +/- 2.4% and 267.5 +/- 12.6% that of control cells, respectively (P < 0.0001 in each instance). In addition, the hPL messenger RNA (mRNA) contents of the IL-6-exposed cells after 3 and 6 days of exposure were 2.2- and 4.7-fold that of control cells. The stimulatory effect of IL-6 on hPL release and hPL mRNA levels was dose dependent, with a minimal effective dose of 50 U/ml. IL-1 beta, which is known to stimulate IL-6 production by human trophoblast cells, also stimulated dose-dependent increases in hPL release and hPL mRNA levels. IL-6 (500 U/ml) had no effect on trophoblast differentiation, but stimulated a 20-fold increase in hPL promoter activity in BeWo choriocarcinoma cells transfected transiently with a plasmid containing 2.3 kilobases of the hPL promoter coupled to the chloramphenicol acetyltransferase gene. In addition, BeWo cells exposed to IL-6 (500 U/ml) for 3 and 6 days contained 2.4- and 3.2-fold more hPL mRNA levels than control cells. Because placental macrophages and syncytiotrophoblast cells release IL-6, these results strongly suggest an autocrine/paracrine role for IL-6 in the regulation of hPL release. The increase in hPL release appears to be due at least in part to an increase in hPL gene expression.

Cell Differentiation↗

Regulation of human placental lactogen expression by 1,25-dihydroxyvitamin D3.

The human placenta synthesizes 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and expresses the vitamin D receptor (VDR), but the roles of 1,25-(OH)2D3 and the VDR in placental physiology are poorly understood. In this study, we have demonstrated that 1,25-(OH)2D3 stimulates the synthesis and release of human placental lactogen (hPL), one of the major secretory products of syncytiotrophoblast cells. Enzymatically dispersed trophoblast cells from term placentas exposed continuously to 1,25-(OH)2D3 (0.1, 6, and 37 microM) for 5 days released significantly more hPL than control cells after the third day of exposure. On days 4 and 5, the amounts of hPL released by cells exposed to 1,25-(OH)2D3 were 2.54- and 4.14-fold that of control cells (P < 0.001 in each instance). The stimulation by 1,25-(OH)2D3 was dose dependent and was accompanied by stimulation of hPL messenger RNA levels. Transient transfection studies of BeWo choriocarcinoma cells transfected with hPL promoter constructs coupled to the chloramphenicol acetyltransferase reporter gene indicated that the stimulation of hPL expression is due at least in part to stimulation of hPL gene expression. Deletion analysis studies of the hPL promoter indicated that a region between -500 to -1200 basepairs is necessary for 1,25-(OH)2D3 responsiveness. Analysis of this region shows a consensus vitamin D response element (VDRE) DNA-binding site of a direct repeat motif separated by three bases. Ligation of this placental VDRE site into a heterologous chloramphenicol acetyltransferase vector caused 1,25-(OH)2D3 responsiveness. Moreover, mobility shift assays demonstrated binding of VDR to placental VDRE. These results indicate that 1,25-(OH)2D3 stimulates the synthesis and release of hPL by a mechanism involving hPL gene transcription and support a role for vitamin D and the VDR in placental function.

Base Sequence↗

Nosocomial outbreak due to Enterococcus faecium highly resistant to vancomycin, penicillin, and gentamicin.

In October 1990, Enterococcus faecium that was highly resistant to glycopeptides, penicillins, and aminoglycosides was isolated from the peritoneal dialysis fluid from a patient in an intensive care unit. Over the following 6 months, multiresistant E. faecium organisms were isolated from cultures of blood, urine, or surgical wound specimens from eight additional patients. Surveillance cultures of groin and/or rectal swabs were positive for eight of 37 patients and four of 62 employees at risk. Restriction endonuclease digestion of chromosomal DNA from outbreak isolates was consistent with dissemination of a single strain throughout the intensive care unit. Strict infection control interventions contained the outbreak after several weeks. Review of patient charts suggested that renal insufficiency, length of hospital stay, duration of antibiotic treatment, and prior treatment with vancomycin were risks for infection due to multiresistant E. faecium. The emergence of multiple-drug-resistant enterococci presents serious infection control and therapeutic dilemmas.

Aged↗

Endothelin inhibits basal and stimulated release of prolactin by human decidual cells.

Recent studies have shown that the basal release of PRL from anterior pituitary cells is inhibited by endothelin-1 (ET-1) and ET-3. To determine whether ET also regulates the synthesis and release of PRL by decidual cells, we examined the effects of ET on the synthesis and release of PRL from an enriched fraction of human decidual cells prepared by isopycnic centrifugation of enzymatically dispersed term decidual tissue. Exposure of decidual cells to ET-1 (10(-7) M) for 96 h caused a progressive decrease in basal PRL synthesis and release beginning 24 h after exposure with half-maximal inhibition occurring at an ET-1 concentration of 5 x 10(-9) M. Between 72-96 h of culture, ET-1-exposed cells synthesized 37.2 +/- 2.7% (SEM) and released 32.3 +/- 1.3% less PRL than control cells (P < 0.01). ET-1-exposed cells incubated with [35S]methionine between 72-96 h also released less [35S] PRL than control cells. Sarafotoxin S6C, an ETB receptor agonist, also inhibited basal PRL release, whereas BQ-123, an ETA receptor antagonist, had no effect on basal or on ET-1-mediated inhibition of PRL release. ET-1 also markedly inhibited the stimulation of PRL synthesis and release in response to insulin and insulin-like growth factor-1 (IGF-1). Cells exposed to insulin (100 ng/ml) and IGF-1 (50 ng/ml) alone released 61.2 +/- 3.6% and 40.0 +/- 3.8% more PRL, respectively, than control cells between 72-96 h of exposure. However, cells exposed simultaneously to insulin and ET-1 (10(-7) M) released only 17.1 +/- 3.5% more PRL than control cells during the same time period, and cells exposed simultaneously to IGF-1 and ET-1 released only 4.1 +/- 1.8% more PRL than controls during the same time interval (P vs. insulin or IGF-1 alone < 0.001 in each instance). Both basal and insulin- and IGF-1-stimulated PRL release were also inhibited by the ET isotypes ET-2 and ET-3, and by the ET-1 precursor, big ET. Since macrophages and decidual cells synthesize ET, and decidual tissue contains specific receptors for ET, the inhibitory action of ET on basal and stimulated PRL release may result from an autocrine and/or paracrine effect and appears to be mediated through the ETB receptor.

Cells, Cultured↗

Insulin-like growth factor-I (IGF-I) enhanced proteolysis of IGF-binding protein-4 in conditioned medium from primary cultures of human decidua: independence from IGF receptor binding.

Previous studies demonstrated that human decidual cells release insulin-like growth factor-binding protein (IGFBP)-1, IGFBP-2, and a 24-kilodalton (kDa) IGFBP in culture. The accumulation of 24-kDa IGFBP, as assessed by ligand blot analysis, decreased when the cells were exposed to IGF-I, but the mechanism was not explored. In the present study, we observed that the IGF-I-mediated decrease in IGFBP-4 accumulation could be explained by increased IGFBP-4 proteolysis. Analysis by IGFBP-4 immunoblotting demonstrated a decline in 24-kDa IGFBP-4 accompanied by a marked increase in a 17- to 18.5-kDa IGFBP-4 fragment(s). In addition, when medium from IGF-I-treated cells was incubated with rat IGFBP-4, the decrease in IGFBP-4 was inhibited by chelators of divalent cations and inhibitors of serine proteases. IGF-I enhancement of IGFBP-4 proteolysis occurs independent of the type I IGF receptor. [Leu24,1-62]IGF-I, an analog with reduced receptor affinity, mimicked the effect of native IGF-I in cell culture. Additionally, alpha-IR3, a monoclonal antibody to the type I IGF receptor, did not block the effect of IGF-I. When IGF-I was incubated with medium from control cells, there was a marked decrease in 24-kDa IGFBP-4 levels and a concomitant increase in levels of a 17- to 18.5-kDa fragment(s), suggesting that IGFBP-4 complexed with IGF-I is more susceptible to proteolysis than IGFBP-4 alone. Together, these findings suggest a novel mechanism for regulation of IGF-I action in the decidua.

Carrier Proteins↗