scholarly journals Expression of insulin, insulin-like growth factor I and glucocorticoid receptor in rat uterus and embryo during decidualization, implantation and organogenesis

Reproduction ◽  
2003 ◽  
pp. 75-84 ◽  
Author(s):  
ET Korgun ◽  
G Dohr ◽  
G Desoye ◽  
R Demir ◽  
UA Kayisli ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucocorticoid Receptor ◽  
Receptor Expression ◽  
Metabolic Effects ◽  
Insulin Like Growth Factor ◽  
Mammalian Embryo ◽  
Endometrial Stromal Cells ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The significance of insulin, insulin-like growth factor I (IGF-I) and glucocorticoids to the early mammalian embryo is clear in that they are key regulators of both mitogenic and metabolic effects during development. In the present study, the temporal sequence of expression of the respective receptor proteins was investigated for the first time in the developing rat utero-embryonic unit between conception and day 12 of gestation using immunocytochemistry. Insulin, IGF-I and glucocorticoid receptor were expressed in embryonic tissues after the start of implantation, and were co-localized in the primary ectoderm, extraembryonic ectoderm as well as in the ectoplacental cone. The parietal endoderm was devoid of glucocorticoid receptor staining, whereas IGF-I receptor was absent in visceral endoderm. After completion of basic organogenesis, the neural tube, notochord, otic placode, Wolffian duct, mesonephros and intestinal tube expressed insulin, IGF-I and glucocorticoid receptor. The glucocorticoid receptor was not expressed in heart tube and dorsal aortae. Considerable amounts of insulin receptor were detected in trophoblast-derived giant cells. In the uterus, luminal epithelium, endometrial stromal and myometrial smooth muscle cells immunoreacted with antisera against insulin, IGF-I and glucocorticoid receptor. Endometrial glands remained negative for the glucocorticoid receptor throughout the gestational period investigated. Uterine hormone receptor expression reached a peak at days 4 and 5 of gestation in endometrial stromal cells and decidua, respectively. In conclusion, the demonstrated ontogenetic pattern of insulin, IGF-I and glucocorticoid receptor expression indicates the potential sites of biological action of the respective ligands, providing supportive evidence for their critical importance during the course of embryogenesis in rats.

Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A

1994 ◽  
Vol 131 (3) ◽  
pp. 251-257 ◽  
Author(s):  
Peter D Zenobi ◽  
Yvonne Glatz ◽  
Annamarie Keller ◽  
Susanne Graf ◽  
Silvia E Jaeggi-Groisman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Type A ◽  
Metabolic Effects ◽  
Insulin Like Growth Factor ◽  
Severe Insulin Resistance ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Zenobi PD, Glatz Y, Keller A, Graf S, Jaeggi-Groisman SE, Riesen WF, Schoenle EJ, Froesch ER. Beneficial metabolic effects of insulin-like growth factor I in patients with severe insulin-resistant diabetes type A. Eur J Endocrinol 1994;131:251–7. ISSN 0804–4643 Severe insulin resistance type A is due to mutations in the insulin receptor gene and is characterized by glucose intolerance or diabetes mellitus, despite extreme hyperinsulinemia, virilization and acanthosis nigricans. At present, there is no therapy for this condition. Recently, we showed that glucose levels in three such patients are promptly lowered by an iv bolus of recombinant human insulin-like growth factor I (rhIGF-I). In the present study, we investigated two of these rare patients again and determined fasting and postprandial glucose, insulin, C-peptide, proinsulin and lipid levels during five control, five treatment and three wash-out days while on a constant diet. Treatment consisted of 2 × 150 μg rhIGF-I/kg sc per day, which elevated total IGF-I levels 4.5-fold above the control. Fasting glucose levels (days 1–5) in the two patients were 9.6±1.3 and 9.2 ± 1.2 mmol/l, respectively, and fell to 4.4±0.4 and 5.1±0.5 mmol/l on treatment days 8–10. Fasting insulin (2950±450 and 690±125 pmol/l), C-peptide (2217±183 and 1317±235 pmol/l) and proinsulin control levels (125±35 and 66±0 pmol/l) also decreased by ~65% during rhIGH-I treatment, as did the respective postprandial levels. Lipid levels hardly changed at all. In conclusion, IGF-I appears to correct partially some metabolic sequelae of severe insulin resistance and may, hence, be used as a new therapeutic agent. E Rudolf Froesch, Department of Internal Medicine, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland

110 DEVELOPMENTAL CHANGES IN ACTIONS OF INSULIN-LIKE GROWTH FACTOR-I IN THE PREIMPLANTATION BOVINE EMBRYO-RECEPTOR EXPRESSION AND THERMOTOLERANCE

2009 ◽  
Vol 21 (1) ◽  
pp. 155 ◽  
Author(s):  
A. Q. Bonilla ◽  
P. J. Hansen
Keyword(s):  
Growth Factor ◽  
Heat Shock ◽  
Least Squares ◽  
Receptor Expression ◽  
Bovine Embryo ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Rabbit Polyclonal Antibody ◽  
Growth Factor I

Insulin-like growth factor-I (IGF-I) can affect function of the preimplantation bovine embryo by increasing the proportion of cultured embryos that become blastocysts, reducing effects of heat shock on development and apoptosis, and enhancing survival of embryos transferred into heat-stressed recipients. At Day 5 postinsemination (pi), the embryo is sensitive to IGF-I as determined by activation of the phosphatidylinositol 3-kinase/Akt pathway and activation of thermoprotective mechanisms. It is not known how early in development IGF-I can affect embryo physiology. The overall objective of the present study was to determine whether IGF-I protects two-cell embryos from heat shock. In the first experiment, the presence of the IGF-I receptor (IGF-IR) was evaluated by immunofluorescence using a rabbit polyclonal antibody against a synthetic peptide of the human IGF-IRβ subunit. Specific labeling for IGF-IR was observed for two-cell embryos (n = 20) and embryos ≥16 cells collected at Day 5 pi (n = 17). In the second experiment, it was tested whether IGF-I would protect two-cell embryos from heat shock. Two-cell embryos were collected at 28 hpi and cultured ±100 ng mL–1 recombinant human IGF-I. After 1 h, embryos were heat-shocked (41°C for 15 h and 38.5°C for 9 h) or maintained at 38.5°C for 24 h. Embryos were then washed to remove IGF-I and cultured in KSOM-BE2 until Day 8 pi. The percent of embryos that became blastocysts at Day 8 was reduced by heat shock (P < 0.005) but was not affected by IGF-I or IGF-I v. heat shock. The least-squares means for percent blastocyst was 38.1% (control) v. 19.3% (heat shock) for embryos without IGF-I and 32.8% (control) v. 20.8% (heat shock) for embryos cultured with IGF-I (n = 11 replicates, n = 169–174 embryos/group; SEM = 2.0%). The third experiment was performed to verify that IGF-I protects Day 5 embryos from heat shock. Embryos ≥16 cells were collected at Day 5 pi and cultured ±100 ng mL–1 IGF-I. After 1 h, embryos were heat-shocked (42°C for 15 h and 38.5°C for 9 h) or maintained at 38.5°C for 24 h. Embryos were washed and cultured in KSOM-BE2 until Day 8 pi. The percent of embryos that became blastocysts was reduced by heat shock (P < 0.001) and increased by IGF-I (P < 0.05). The least-squares means for percent blastocyst at Day 8 pi was 86.9% (control) v. 47.7% (heat shock) for embryos without IGF-I and 88.7% (control) v. 66.3% (heat shock) for embryos cultured with IGF-I (n = 4 replicates, n = 59–60 embryos/group; SEM = 5.6%). In conclusion, IGF-I does not induce thermotolerance in two-cell embryos despite the presence of IGF-IR. Support: USDA NRI 2007-35203-18070 and BARD US-3986-07.

Pituitary and hypothalamic insulin-like growth factor-I (IGF-I) and IGF-I receptor expression in food-deprived rats

1993 ◽  
Vol 93 (2) ◽  
pp. 193-198 ◽  
Author(s):  
David Olchovsky ◽  
Jinfen Song ◽  
Marie C. Gelato ◽  
Jennifer Sherwood ◽  
Elizabeth Spatola ◽  
...  
Keyword(s):  
Growth Factor ◽  
Receptor Expression ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Evidence against a direct effect of leptin on insulin-like growth factor-I (IGF-I), IGFBP-2 and IGF-I receptor expression in human SK-N-MC neuroepithelioma cells

2005 ◽  
Vol 130 (1-2) ◽  
pp. 35-41 ◽  
Author(s):  
Wieland Kiess ◽  
Jürgen Klammt ◽  
Jörg Hänze ◽  
Werner F. Blum ◽  
Antje Berthold ◽  
...  
Keyword(s):  
Growth Factor ◽  
Direct Effect ◽  
Receptor Expression ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

scholarly journals The insulin-like growth factor I receptor is overexpressed in psoriatic epidermis, but is differentially regulated from the epidermal growth factor receptor.

1992 ◽  
Vol 175 (4) ◽  
pp. 1081-1090 ◽  
Author(s):  
J F Krane ◽  
A B Gottlieb ◽  
D M Carter ◽  
J G Krueger
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Epidermal Growth ◽  
Growth Factor I

Insulin-like growth factor I (IGF-I)/somatomedin C is an important mediator of keratinocyte growth in vitro, and the expression of IGF-I receptors in the basal layer of normal epidermis suggests that this growth pathway may function in the regulation of keratinocyte growth in vivo as well. The pattern of IGF-I receptor expression in normal skin is distinct from that of the epidermal growth factor (EGF) receptor, suggesting that these receptors might be differentially regulated. The purpose of this study was to obtain a better understanding of IGF-I receptor function in the skin by examining IGF-I receptor expression in psoriatic epidermis and in cultured human keratinocytes. Our findings indicate that IGF-I receptor expression is increased in psoriasis as measured by protein tyrosine kinase assays of biopsy extracts and by immunohistochemical staining with an IGF-I receptor-specific monoclonal antibody. Unlike EGF receptor expression, which is also increased in psoriatic epidermis, the pattern of IGF-I receptor expression corresponds closely with the increased size of the keratinocyte proliferative compartment in psoriasis. Biochemical agents that diminish EGF receptor ligand binding (phorbol ester or calcium ionophore treatment) produce opposite effects on the IGF-I receptor. These results suggest that cellular expression and differential regulation of both growth factor receptor systems may control critical aspects of epidermal proliferation or function.

Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency

1994 ◽  
Vol 131 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Maria C Thorén ◽  
Inga-Lena Wivall-Helleryd ◽  
Werner F Blum ◽  
Kerstin E Hall
Keyword(s):  
Growth Factor ◽  
Subcutaneous Administration ◽  
Metabolic Effects ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Recombinant Human Insulin ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Igfbp 3

Thorén MC, Wivall-Helleryd I-L. Blum WF, Hall KE. Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency. Eur J Endocrinol 1994;131:33–40. ISSN 0804–4643 Insulin-like growth factor I (IGF-I) circulates bound to specific binding proteins (BPs) that modulate its effects at target cells. Hypoglycemia alters the serum levels of insulin-dependent IGFBPs and thus modifies the IGF-I action. We administered recombinant IGF-I (40 μg/kg body wt, from Kabi Pharmacia) in a morning dose (08.00 h) for seven consecutive days to six patients (21–47 years) with panhypopituitarism. This dose did not lead to hypoglycemia. Repeated blood sampling was performed on days 1 and 7, otherwise morning samples were drawn. The mean serum total IGF-I was maximal 3–4 h after the injection. A higher peak and basal value (p < 0.05) was observed on day 7 when compared to that observed on day 1. The concentrations were 237 vs 190 μg/l and 43 vs 22 μg/l. The mean free IGF-I increased concomitantly to 17 and 20 μg/l after 2–3 h on days 1 and 7. After 4 h, IGF-II was decreased (p <0.05) from 340 to 291 μg/l on day 1 and from 341 to 252 μg/l on day 7. The IGF-I area under the curve on days 1 and 7 was correlated to the IGFBP-3 levels. Only the patient with the highest IGFBP-3 level obtained IGF-I levels above 100 μg/l for 24 h. In spite of unchanged glucose levels, there was a modest suppression of insulin levels (p < 0.05) between 0 and 4 h from 102 to 78 pmol/l on day 1 and from 90 to 60 pmol/l on day 7 when the subjects were fasting. A small decline of mean potassium concentrations was found 2–6 h after the injection on day 1. During a week with daily injections, the morning serum IGF-I increased slightly in comparison to basal levels but no significant change in morning values of IGFBP-1, -2, -3, glucose and insulin were observed. Serum urea, creatinine, cholesterol and free fatty acid decreased significantly, indicating metabolic effects of IGF-I. Thus IGF-I has metabolic effects in doses not leading to hypoglycemia. To achieve a normal diurnal IGF-I level, recombinant IGF-I should be administered two or three times per 24 h in subjects with subnormal IGFBP-3 levels. Marja Thorén, Department of Endocrinology and Diabetology, Karolinska Hospital, S-171 76 Stockholm, Sweden

Diverse effects of insulin-like growth factor I on glucose, lipid, and amino acid metabolism

1992 ◽  
Vol 262 (1) ◽  
pp. E130-E133 ◽  
Author(s):  
S. D. Boulware ◽  
W. V. Tamborlane ◽  
L. S. Matthews ◽  
R. S. Sherwin
Keyword(s):  
Insulin Secretion ◽  
Amino Acid ◽  
Growth Factor ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Effects ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

The metabolic effects of recombinant human insulin-like growth factor I (rhIGF-I) on glucose, amino acid, and free fatty acid (FFA) metabolism were examined in nine healthy nonobese subjects. Each received a 3-h primed continuous infusion of rhIGF-I (20 micrograms/kg bolus, 0.4 microgram.kg-1.min-1) while maintaining euglycemia using an exogenous glucose infusion. Total IGF-I levels increased from 125 +/- 11 to 444 +/- 22 ng/ml, and free IGF-I levels rose from undetectable to 73 +/- 5 ng/ml. Insulin levels fell from 95 +/- 9 to 64 +/- 8 pM, and C-peptide fell from 453 +/- 48 to 206 +/- 29 pM; circulating glucagon levels also declined from 72 +/- 9 to 42 +/- 4 pg/ml, rhIGF-I produced a two- to threefold increase in glucose uptake as measured by [3H] glucose (from 10.3 +/- 0.6 to 27.4 +/- 3 mumol.kg-1.m-1), and, despite the fall in insulin secretion, there was a marked 60-70% inhibition of hepatic glucose production. Furthermore, FFA and branched-chain amino acids declined by 40-60% (411 +/- 58 to 165 +/- 36 and 406 +/- 23 to 219 +/- 14 microM, respectively). Our data demonstrate that rhIGF-I has potent effects on glucose (hepatic and peripheral), lipid, and amino acid metabolism in normal humans. The scope of the actions of rhIGF-I closely resemble those of insulin, despite a concomitant inhibitory effect on insulin secretion.

Co-ordinate actions of FSH and insulin-like growth factor-I on LH receptor expression in rat granulosa cells

1994 ◽  
Vol 141 (2) ◽  
pp. 301-308 ◽  
Author(s):  
M Kanzaki ◽  
M-A Hattori ◽  
R Horiuchi ◽  
I Kojima
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Granulosa Cells ◽  
Receptor Expression ◽  
Continuous Exposure ◽  
Insulin Like Growth Factor ◽  
Lh Receptor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Abstract The actions of FSH and Insulin-like growth factor-I (IGF-I) were studied in cultured rat ovarian granulosa cells. Cells became differentiated and expressed LH receptors when they were incubated for 72 h with 200 μg FSH/l (high FSH) but not 20 μg FSH/l (low FSH). Treatment with high but not low FSH increased the release of both immunoreactive and bioactive IGF-I into the medium. A combination of low FSH and IGF-I reproduced the effect of high FSH on LH receptor expression. We then examined the critical time when low FSH and IGF-I exerted their effects. In the presence of continuous low FSH, IGF-I was capable of inducing LH receptor expression even when added 24 h after the addition of low FSH. However, when IGF-I was added at 36 h, LH receptor expression measured at 72 h was greatly reduced. In contrast to the action of IGF-I, continuous exposure to low FSH was required for LH receptor expression, and IGF-I had no effect when FSH was not included for the entire 72 h of culture. DNA synthesis as assessed by both [3H]thymidine incorporation and nuclear bromodeoxyuridine labelling was moderate at the beginning of culture and markedly reduced at 24 h both in the presence and absence of either high FSH or low FSH plus IGF-I. In the presence of either high FSH or a combination of low FSH plus IGF-I, DNA synthesis remained decreased for up to 72 h whereas it began to increase in the absence of either high FSH or a combination of low FSH plus IGF-I. A similar increase in DNA synthesis was observed after 48 h when granulosa cells were treated with low FSH alone, which did not induce LH receptor expression. These results indicate that 1) growth and differentiation of granulosa cells are regulated inversely; 2) FSH and IGF-I act together to induce LH receptor expression; and 3) action of IGF-I is dependent on the presence of FSH. Journal of Endocrinology (1994) 141, 301–308

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