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L J Murphy

Publications and source records attributed to L J Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1994

Insulin and glucocorticoids regulate IGFBP-1 expression via a common promoter region.

Hepatic expression of insulin-like growth factor binding protein-1 is regulated by insulin and glucocorticoids. To study underlying mechanisms, rat hepatocytes in primary culture were transfected with deletion mutants and heterologous promoter constructs, identifying a 41 bp region of the rat insulin-like growth factor binding protein-1 promoter which is sufficient to mediate regulation by both insulin and glucocorticoids. Half maximal suppression of promoter activity by insulin occurred at a physiologic concentration, 5 x 10(-10) M, and regulation by insulin was dominant in that insulin suppressed promoter activity at all dexamethasone concentrations. Transfection of rat hepatocytes in primary culture should be a useful approach for exploring the regulation of gene expression by insulin.

Animals↗
PubMed1994

Kainic acid induced alterations in antibody recognition of connexin43 and loss of astrocytic gap junctions in rat brain.

Intracerebral administration of kainic acid (KA) in rats was previously shown to abolish immunohistochemical labelling for the astrocytic gap junction protein connexin43 (Cx43) at sites depleted of neurons (Vukelic et al: Neurosci Lett 130:120-124, 1991). This response of Cx43 has now been further investigated with a number of different sequence-specific anti-Cx43 antibodies. At lesion sites in the thalamus, striatum, and hippocampus examined immunohistochemically with an antibody against amino acids (aa's) 346-363 in the Cx43 sequence, the antibody used in the earlier study, Cx43-immunoreactivity was increased 5 h after KA injections, absent by 24 h and for up to 2 weeks post-injection, and began to return to less than normal levels by 2 to 3 weeks post-injection. Analyses of KA lesion sites with antibodies against other sequences of Cx43 (amino acids 283-298, 253-270, 241-260, 113-123, and 49-61) revealed not only the presence but in some cases an increased density of Cx43 immunoreactivity after a survival time of 1 week. Immunolabelling patterns at these sites consisted of relatively large, coarse profiles rather the fine punctate labelling typically seen in sections of normal brain. In homogenates of KA-injected striatum analyzed by Western blots, Cx43 was detected at near normal or slightly increased levels at various survival times examined. The 43 kDa phosphorylated form of Cx43 and its faster migrating 41 kDa dephosphorylated form which is generated post-mortem by a brain phosphatase were both present after standard methods of tissue preparation for Western blot analysis, while only the 43 kDa form was present in normal and KA-injected striatum after inactivation of brain metabolism by focused cranial microwave irradiation. Ultrastructural investigations of lesions sites within the thalamus revealed a virtual absence of astrocytic gap junctions. These results demonstrate that Cx43 levels initially increase after intracerebral KA treatment, that its molecular organization in resident astrocytes is altered such that epitopes that are normally accessible to antibody are hidden while those that may be hidden or relatively inaccessible are exposed, and that this molecular alteration in Cx43 is associated with loss of astrocytic gap junctions.

Animals↗
PubMed1994

Expression of insulin-like growth factor binding proteins by T-47D human breast cancer cells: regulation by progestins and antiestrogens.

We have used ligand blotting and Northern blotting techniques to examine the effects of progestins and antiestrogens on expression of insulin-like growth factor binding proteins (IGFBPs) by T-47D human breast cancer cells under conditions where these agents are growth inhibitory. Under basal conditions, conditioned medium from T-47D cells was found to contain IGFBPs of 39, 33, and 27 kDa. Northern blot and/or Western blot analysis have identified these as IGFBP 2, 5, and 4, respectively. Medroxyprogesterone acetate (MPA) treatment resulted in a time- and dose-dependent decrease in IGFBP 4 and 5 mRNA abundance and secretion of these proteins, while little if any effect was observed on IGFBP 2 expression. A decrease in the steady state mRNA levels for IGFBP 4 and 5 was observed with as little as 0.1 nM MPA. Using 10 nM MPA a maximum decrease in IGFBP 4 and 5 mRNA levels was observed between 12 and 24 hours. While RU 486 alone had little or no effect on IGFBP 4 expression, it inhibited the effect of MPA. However, in the same samples, IGFBP 5 expression was inhibited by RU 486, and RU 486 was unable to reverse the effects of progestins on the expression of IGFBP 5. Furthermore, another synthetic progestin, Org 2058, but not dexamethasone, inhibited IGFBP 4 and IGFBP 5 expression. The antiestrogen ICI 164384 also transiently decreased the steady state mRNA levels of both IGFBP 4 and IGFBP 5. Regulation of expression of the IGFBPs by these agents suggests a potential role for the IGFBPs in the growth response of T-47D cells to these agents.

Breast Neoplasms↗
PubMed1994

The pituitary-muscle axis in mdx dystrophic mice.

As myogenesis, muscle growth and differentiation and growth factor expression are influenced by thyroid and growth hormone (GH) levels, it is important to investigate the possibility that altered activity of the pituitary-muscle axis prevents the lethal progression of mdx dystrophy and/or contributes to the muscle fiber hypertrophy of limb muscles. The ultrastructure of pituitary and thyroid tissues in age-matched control and mdx mice at 2 and 12 months of age was examined. Pituitary GH, and serum thyroid stimulating hormone (TSH), thyroid hormone (T4), and creatine kinase (CK) levels were measured. Mdx thyroid gland structure was similar to age-matched control glands. Mdx thyroid gland weighed significantly more than in age-matched controls, but was unchanged relative to body weight. TSH and T4 levels were not different from levels in control mice. High CK levels reflected the active dystrophy in mdx muscles. Somatotrophs in mdx pituitaries were hypertrophied in comparison to controls, indicating increased secretory activity, and pituitary GH was slightly but significantly greater in old mdx female mice compared to age-matched female controls. These observations rule out hypopituitary or hypothyroid function as a reason for the low impact of dystrophin deficiency in mdx muscles. Results suggest a contribution by raised GH to the fiber hypertrophy in mdx limb and heart muscle, which might also assist the large capacity for limb muscle regeneration in mdx mice.

Aging↗
PubMed1994

Hormonal regulation of proliferation and transforming growth factors gene expression in human endometrial adenocarcinoma xenografts.

We have previously shown that estrogen and progestins regulate both cellular proliferation and transforming growth factor (TGF) expression in human endometrial adenocarcinoma cells in vitro. In the current study we examined the regulation of TGF-alpha and -beta 1 expression in endometrial adenocarcinoma xenografts. Four human endometrial adenocarcinoma cell lines were inoculated into female BALB/c nude mice. Administration of 17 beta-estradiol (E2) increased tumor size in intact mice inoculated with Ishikawa, HEC-50 and HEC-1B cells but inhibited growth of HEC-1A xenografts. 4-Hydroxy tamoxifen (OH-Tam) had similar effects to E2 in animals carrying Ishikawa and HEC-1A cell xenografts but had no significant effect on growth of HEC-50 or HEC-1B xenografts. In intact mice inoculated with OH-Tam pellets and Ishikawa cells, the tumors were larger and had lower levels of TGF-alpha mRNA than in untreated or E2 treated mice. In mice carrying Ishikawa, HEC-50 and HEC-1B cell xenografts none of the hormones or agents tested altered TGF-beta 1 mRNA levels. In contrast, both E2 and OH-Tam significantly increased xenografts TGF-beta 1 mRNA levels in HEC-1A xenografts as well as significantly reduced tumor size. Medroxyprogesterone acetate (MPA) had no effect on tumor size of Ishikawa, HEC-1A and HEC-1B cell cell xenografts but significantly increased the size of HEC-50 xenografts. MPA significantly reduced TGF-alpha expression in Ishikawa cell xenografts but had no effect in the other cell xenografts. MPA had no effect on TGF-beta 1 expression in any of the xenografts. These observations demonstrate a discordance between the hormonal effects on TGF expression and cellular proliferation and argue against a major role for the TGFs in regulation of human endometrial adenocarcinoma cell proliferation in vivo.

Adenocarcinoma↗
PubMed1994

Growth factors and steroid hormone action in endometrial cancer.

There is compelling evidence that growth factors are involved in mediating estrogen action in target tissues. The role of growth factors in the development and progression of endometrial cancer is less clear. Steroid hormones can regulate the expression of the transforming growth factors and epidermal growth factor receptors in endometrial cancer cells in culture. It is also possible to demonstrate that these growth factors function in an autocrine fashion to regulate proliferation of endometrial cancer cells in culture. Constitutive expression or overexpression of such autocrine/paracrine factors and/or their receptors may be important in the growth progression of endometrial neoplasia. However, to date the evidence to support the hypothesis is limited.

Endometrial Neoplasms↗
PubMed1994

Phosphorylated forms of connexin43 predominate in rat brain: demonstration by rapid inactivation of brain metabolism.

The gap junction protein connexin43 (Cx43) has been reported to exist as several phosphorylated forms migrating at approximately 43 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as well as an unphosphorylated 41-kDa form. In brain, Cx43 is expressed predominantly in astrocytes and is also expressed in several other cell types. Whereas the phosphorylated forms of Cx43 predominate in heart, several studies have indicated that high levels of the unphosphorylated form of Cx43 are present in brain. Various experiments in this report indicate that the 41-kDa molecular form in brain is a postmortem dephosphorylation product of phosphorylated Cx43. In rats killed by cranial high-energy microwave irradiation leading to rapid inactivation of brain metabolism, Cx43 in cerebral cortex was present almost exclusively as the 43-kDa phosphorylated form. Rapid dissection of brain followed by heat treatment or inclusion of phosphatase inhibitors during tissue homogenization also largely prevented the conversion of the 43- to the 41-kDa form. The 41-kDa species was generated after alkaline phosphatase digestion of the 43-kDa material obtained by immunoprecipitation from microwave-irradiated brain. Immunolabeling patterns and relative regional levels of Cx43 as seen by immunohistochemical and western blot detection were the same whether or not metabolism to the 41-kDa species was prevented. In developing rat brain, Cx43 levels in frontal cortex and brainstem increased with age, but the degree of dephosphorylation of the 43- to the 41-kDa form was greater at earlier ages in the brainstem. It appears that brain contains a phosphatase that may be involved in modulating the phosphorylation state of Cx43 and thus may regulate intercellular communication via astrocytic gap junctions.

Alkaline Phosphatase↗
PubMed1994

Generation by the phosphoramidon-sensitive peptidases, endopeptidase-24.11 and thermolysin, of endothelin-1 and c-terminal fragment from big endothelin-1.

1. Phosphoramidon, a potent inhibitor of endopeptidase-24.11 (E-24.11) and thermolysin, has been shown to reduce the hypertensive effect of exogenous big endothelin-1 (big ET-1) in rats. To examine whether E-24.11 or thermolysin convert big ET-1 to endothelin-1 (ET-1) and C-terminal fragment (CTF), the effects on porcine and human big ET-1 of each of the purified enzymes were compared in vitro. 2. For E-24.11, the relative rates of hydrolysis were ET-1 > CTF >> big ET-1. The relative half-lives for hydrolysis of 3 nmol of each peptide by 200 ng enzyme were: big ET-1 > 24 h; ET-1, 37 min; CTF, 57 min. For comparison, the half-life for hydrolysis of substance P under similar conditions was 2.1 min. 3. For thermolysin the relative rates of hydrolysis were found to be big ET-1 > CTF > ET-1. The relative half-lives for hydrolysis of 3 nmol peptide by 50 ng enzyme were: big ET-1, 25 min; ET-1, 56 min; CTF, 47 min. 4. Because the low rate of conversion of big ET-1 to ET-1 by E-24.11 did not yield sufficient ET-1 for h.p.l.c. quantification a RIA specific for ET-1(16-21) was used to study further the hydrolysis of big ET-1 by E-24.11. Incubation of big ET-1 (0.2-2 nmol) with E-24.11 (4-400 ng) generated ET-1 levels of between 1.7 and 33 pmol measured by RIA. Incubation of big ET-1 (2 nmol) with E-24.11 (40 ng) for 8 h showed that steady state levels of ET-1 were achieved after 4 h indicating that the rate of ET-1 degradation was then equal to the formation of new ET-1. Characterization of the immunoreactivity by h.p.l.c. and RIA confirmed that authentic ET-1 had been produced, but the yield was insufficient for verification by mass spectrometry.5. Both ET-l-like and CTF-like peaks were detected at 214 nm when the products of big ET-1 hydrolysis by thermolysin were resolved by h.p.l.c. RIA and mass spectrometry confirmed the production of ET-1 with amounts in the range 120-160 pmol.6. The hydrolysis profile of ET-1 by E-24.11 and thermolysin shows that both enzymes have some common cleavage sites consistent with their similar specificities hydrolysing on the amino side of a hydrophobic residue.7. Thermolysin, for which 3D structural information is available, may represent a better model for endothelin converting enzyme (ECE) action than E-24.11 and could be useful for the design of ECE inhibitors. Since E-24.11 can both synthesize and hydrolyse ET-1, the presence of E-24.11 in membrane fractions or in partially purified ECE preparations may produce misleading estimates of ECE activity.

Animals↗
PubMed1994

Interdependence of epidermal growth factor and insulin-like growth factor-I expression in the mouse uterus.

Both epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) have been implicated as paracrine mediators of estrogen action in the rodent uterus. Here we have used a semiquantitative reverse transcription-polymerase chain reaction assay to demonstrate the changes in IGF-I messenger RNA (mRNA) and EGF mRNA abundance in response to the unilateral intraluminal administration of 17 beta-estradiol (E2), EGF, and IGF-I. Local administration of EGF to ovariectomized mice significantly increased IGF-I mRNA abundance compared to that in the contralateral saline-injected uterine horn (141.06 +/- 19.04% of control value; mean +/- SEM; n = 7; P = 0.031), comparable to the effect of E2 administration (143.21 +/- 12.47% of control value; n = 7; P = 0.045). Similar results were obtained in immature mice. Pretreatment with the antiestrogen ICI 164,384 completely blocked the E2-induced increase and partially blocked the EGF-induced increase in IGF-I mRNA. Furthermore, intraluminal administration of sheep antibodies to EGF receptor significantly decreased the amount of IGF-I mRNA compared to that in the contralateral sheep immunoglobulin G-treated uterine horn (78.49 +/- 4.33% vs. 100 +/- 2.65%; mean +/- SEM; P = 0.014). Intraluminal administration of IGF-I significantly increased the amount of EGF mRNA in the treated uterine horn (173.33 +/- 18.79% of the control value), whereas it had no effect on IGF-I mRNA abundance. Similarly, intraluminal administration of EGF had no significant effect on uterine EGF mRNA levels. These data provide some insight into the complex interaction of growth factors that occurs in the uterus after E2 administration and suggests that activation of IGF-I expression may be a common down-stream event in both E2- and EGF-induced uterine cellular proliferation. Paracrine actions of EGF, which is expressed predominantly in the epithelial cells, on IGF-I expression by stromal cells and paracrine effects of stromal IGF-I on EGF expression in epithelial cells may facilitate the epithelial-stromal interactions, which are thought to be important in E2-induced endometrial proliferation.

Animals↗
PubMed1994

The regulation of insulin-like growth factor-binding protein 1 messenger ribonucleic acid in cultured rat hepatocytes: the roles of glucagon and growth hormone.

In previous studies it was shown that bovine GH (bGH) suppressed and glucagon stimulated the level of 24- and 30- to 34-kilodalton insulin-like growth factor-binding proteins (IGFBPs) in the media of cultured rat hepatocytes. In the present study we have evaluated the regulation of IGFBP-1 gene expression in primary rat hepatocyte cultures. Glucagon produced a dose-dependent stimulation of hepatocyte IGFBP-1 messenger RNA (mRNA), attaining levels 2- to 6-fold greater than control at a glucagon concentration of 100 ng/ml. GH inhibited the accumulation of IGFBP-1 mRNA in a dose-dependent manner producing, 40-70% inhibition at 50 ng/ml. The effect of glucagon was comparable to and additive with dexamethasone (1 microM). The addition of 3-isobutyl-1-methylxanthine (100 microM) and (Bu)2cAMP (100 microM) augmented IGFBP-1 mRNA levels 5- to 6-fold. 4 beta-Phorbol 12 beta-myristate 13 alpha-acetate (300 nM) was found to inhibit IGFBP-1 mRNA levels by 40-50%. The inhibitory effect of bGH on IGFBP-1 mRNA levels was abolished after preincubation with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (10 microM) for 24 h, whereas glucagon's stimulatory effect was unaffected. The addition of staurosporine (500 nM) and H-7 (1 mM) abolished the inhibitory effect of GH but also significantly inhibited the stimulatory effect of glucagon, a result consistent with these agents acting on both protein kinase C (PKC) and PKA. In the presence of 10 micrograms/ml cycloheximide, IGFBP-1 gene expression was superinduced by bGH, whereas the effect of glucagon was uninfluenced. Thus the inhibitory action of GH involves, in part, the activation of PKC. Glucagon's stimulatory effect seems to involve the activation of PKA. The inhibitory effect of bGH on IGFBP-1 gene expression may require the continuing synthesis of one or more labile protein(s).

1-Methyl-3-isobutylxanthine↗
PubMed1994

Expression of insulin-like growth factors and their binding proteins in the estrogen responsive Ishikawa human endometrial cancer cell line.

In uterine tissue, estrogen regulates various components of the insulin-like growth factor system; however, there are few suitable in vitro systems to examine these effects. Here we have examined the effects of 17-beta estradiol (E2) on expression and synthesis of insulin-like growth factors (IGF-I and IGF-II) and the insulin-like growth factor binding proteins (IGFBPs) by Ishikawa human endometrial cancer cells. Using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, we demonstrated that both E2 and 4-hydroxy-tamoxifen (OHT) enhanced IGF-I expression but had no effect on IGF-II expression. The pure antiestrogen ICI 182,780 had no effect on IGF-I expression and partially blocked the E2 and OHT effect on IGF-I expression. The effect of epidermal growth factor (EGF), which is able to mimic some of the effects of E2 in Ishikawa cells and uterine tissue, was also examined. EGF, unlike E2, did not increase IGF-I expression but rather resulted in a significant decrease in IGF-I messenger RNA (mRNA) levels. EGF also resulted in a small, nonsignificant increase in IGF-II mRNA levels. IGFBP-3, -5, and -6 mRNAs were detected by Northern blot analyses of Ishikawa cells RNA. However, only IGFBP-3 was consistently detected by ligand blotting of conditioned medium. E2 had no significant effect on expression of any of the binding proteins, whereas EGF increased IGFBP-5 mRNA levels. These data provide the first in vitro demonstration of regulation of IGF-I expression by E2. The Ishikawa cell line may provide a useful model to further investigate the molecular mechanisms underlying E2 regulation of IGF-I expression. Furthermore, we have demonstrated a clear dissociation of the effects of E2 and EGF on IGF-I expression in this cell line.

Base Sequence↗
PubMed1994

Generation of des-(1-3) insulin-like growth factor-I in serum by an acid protease.

Des-(1-3) insulin-like growth factor-I (IGF-I), a more potent IGF-I variant, has been isolated from biological fluids and tissue extracts. The mechanisms involved in this posttranslational modification of IGF-I have not been elucidated. In this study we demonstrated the presence in rat serum of an acid protease activity that is capable of generating des-(1-3) IGF-I from intact IGF-I. An assay for measuring this enzyme activity using an immobilized synthetic substrate, biotin-G-P-E-T-L-C, that includes the site of cleavage of intact IGF-I was developed. Using this assay, the time, temperature, and pH dependency of the enzyme activity was investigated. Although some activity was observed under neutral conditions, the optimal pH was pH 5.5. Of a variety of commercially available proteases tested, only trypsin and cathepsin-D had activity. In contrast to the serum enzyme activity, trypsin was more active at pH 7.5 than at pH 5.5, and cathepsin-D resulted in extensive proteolysis of IGF-I. Soybean trypsin inhibitor, alpha 1-antitrypsin, and pepstatin-A were able to partially inhibit the serum enzyme activity. This enzymatic activity was partially purified from serum by acid-ethanol extraction (6-fold) and further purified by pepstatin-A affinity chromatography (200-fold). The partially purified enzyme had characteristics similar to those of the activity measured in serum. The enzymatic conversion of [125I]IGF-I to [125I]des-(1-3) IGF-I in serum was confirmed by immunoprecipitation using antibody to an N-terminal fragment of IGF-I (residues 1-9), which could recognize intact IGF-I, but not des-(1-3) IGF-I (< 3% cross-reactivity), and by size-exclusion HPLC analysis. When [125I]IGF-I was incubated with serum, only the 7.5-kilodalton free IGF-I fraction contained the des-(1-3) IGF-I variant. [125I]des-(1-3) IGF-I was not detected in the 150- to 200- or 50-kilodalton IGF-I-binding protein complexes. These findings demonstrate that des-(1-3) IGF-I can be generated in serum at neutral pH and that this process may be enhanced under the acidic conditions that occur in the pericellular environment.

Animals↗
PubMed1994

Effects of oestrogen on rat uterine expression of insulin-like growth factor-binding proteins.

Previous studies have established that the IGFs are involved in oestrogen-induced uterine proliferation. IGF-binding proteins (IGFBPs) are present in most biological fluids and tissues and may modulate the actions of the IGFs. We examined uterine, hepatic and renal expression of the IGFBPs throughout the oestrous cycle and investigated the effects of oestradiol (OE2) on IGFBP expression in ovariectomized (ovx) rats. Uterine expression of IGFBPs-1 and -3 showed a definite variation throughout the oestrous cycle with highest levels during dioestrus. In the liver and kidney the changes in IGFBP-1 and IGFBP-3 mRNA abundance were the opposite of those observed in the uterus, with the highest levels observed during oestrus. Administration of OE2 to ovx rats decreased uterine IGFBP-3 mRNA and increased IGFBP-4 mRNA levels. In these rats there were no consistent changes in renal IGFBP-1 or IGFBP-3 mRNAs; however, a significant increase in IGFBP-4 mRNA was observed in this tissue, as in the uterus. In the liver an increase in IGFBP-1 mRNA and a decrease in IGFBP-3 mRNA levels were observed in rats treated with OE2. Despite changes in uterine, hepatic and renal IGFBP mRNA levels, no significant variation was seen in serum IGFBPs as determined by ligand blotting of sera. These data demonstrate that there is a cyclical variation in the expression of the IGFBPs in the uterus, kidney and liver, and that OE2 is able to modulate differentially IGFBP expression in these tissues.

Animals↗
PubMed1993

Expression and regulation of insulin-like growth factor binding protein-1 in the rat uterus throughout estrous cycle.

In previous studies, we have demonstrated that IGF-1 and IGF-1 receptor are expressed in rat uterus and that the expression is up-regulated by estrogen. The present study examines the expression and regulation of IGFBP-1 and IGFBP-3 in rat uterus throughout the estrous cycle. The stage of the estrous cycle in 16 mature female rats was determined by microscopic examination of daily prepared vaginal smears. Rat uteri were then used for RNA extraction. The results of the Northern blot analysis demonstrate that uterine cells express both IGFBP-1 and IGFBP-3 mRNA throughout the estrous cycle. When autoradiograms were quantitated by a densitometry, a significant reduction in expression of IGFBP-1 mRNA was found in uteri at stages of proestrous and estrous relative to that in diestrus. Although the level of IGFBP-3 mRNA varied in uteri throughout estrous cycle but this variation was not statistically significant. The lowest expression of IGFBP-1 (8.5% relative to diestrus, p < 0.05, n = 4) and IGFBP-3 (71% relative to diestrus) was found in the uteri prepared from rats at the stage of proestrus, while the highest expression of IGFBP-1 and IGFBP-3 was observed in the uteri obtained from rats at the stage of diestrus and metestrus, respectively. Using anti-rabbit IGFBP-1 antibody raised against an oligo-synthetic IGFBP-1 peptide, immunohistochemical staining demonstrates the presence of IGFBP-1 in the luminal and stromal glandular epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The IGFs and their binding proteins in murine development.

Recent observations suggest that the diverse actions of the insulin-like growth factors (IGFs) are the result of interactions of the various components that make up the IGF system. The components of this system include IGF-I and -II and their variants, the type 1 and 2 IGF receptors and the insulin-like growth factor binding proteins (IGFBPs). Various components of the IGF system are expressed in the developing mouse embryo and the adjacent tissues of the reproductive tract in which the embryo develops. Thus there is the potential for paracrine interactions between the maternal and fetal tissues. Transcripts for the IGF receptors, IGF-I and IGF-II, have been demonstrated in the periimplantation mouse embryo. While there are now data from gene ablation experiments indicating that IGF-II is important in embryogenesis, the role of other components of the IGF system such as the IGFBPs remains unclear. The data accumulated so far are largely empirical, and there is as yet little compelling evidence that maternal IGFs derived from oviduct or uterine fluid and maternal tissues are necessary for normal fetal development. We have started to develop transgenic mice lines overexpressing IGFBPs to attempt to address the role of these binding proteins in fetal development.

Animals↗