Developmentally Regulated Responses of Human Granulosa Cells to Insulin-Like Growth Factors (IGFs):IGF-I and IGF-II Action Mediated Via the Type-I IGF Receptor1

In experimental animal models, insulin-like growth factors (IGFs) have been found to be more potent stimulators of ovarian function than insulin. In human theca cells, however, insulin, IGF-I, and IGF-II have similar effects on androgen production. The relative effects of insulin and IGFs on human granulosa cell steroidogenesis is unknown. Furthermore, it is unclear whether effects of IGF-II on steroidogenesis are mediated by the type-I or type-II IGF receptor. The effects of insulin, IGF-I, and IGF-II on human granulosa cell steroidogenesis were compared in vitro. As expected, insulin, IGF-I, and IGF-II enhanced steroidogenesis. Previously, IGF-II has been shown to enhance granulosa cell steroid production after insulin preincubation. In this study, an effect of IGF-II, independent of insulin priming, also was observed. In granulosa cell cultures from small antral follicles (≤13 mm), insulin and IGF-I stimulated steroid production to a similar degree, whereas IGF-II was less effective. In contrast, IGFs were more effective than insulin (IGF-I > IGF-II > insulin) in granulosa cells isolated from preovulatory follicles. IGF-I and IGF-II actions were mediated via the type-1 IGF receptor. The increased responsiveness of mature granulosa cells to IGFs may be an important mechanism by which granulosa cells increase their steroidogenic output in the preovulatory follicle.

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Developmentally Regulated Responses of Human Granulosa Cells to Insulin-Like Growth Factors (IGFs):IGF-I and IGF-II Action Mediated Via the Type-I IGF Receptor

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.83.4.1256 ◽

1998 ◽

Vol 83 (4) ◽

pp. 1256-1259 ◽

Cited By ~ 12

Author(s):

D. S. Willis

Keyword(s):

Growth Factors ◽

Granulosa Cells ◽

Type I ◽

Developmentally Regulated ◽

Human Granulosa Cells ◽

Type I Igf Receptor ◽

Igf I ◽

Igf Receptor ◽

Insulin Like Growth Factors

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Stimulation of DNA synthesis in chicken muscle satellite cells by insulin and insulin-like growth factors: evidence for exclusive mediation by a type-I insulin-like growth factor receptor

Journal of Endocrinology ◽

10.1677/joe.0.1280035 ◽

1991 ◽

Vol 128 (1) ◽

pp. 35-NP ◽

Cited By ~ 71

Author(s):

M. J. Duclos ◽

R. S. Wilkie ◽

C. Goddard

Keyword(s):

Growth Factors ◽

Satellite Cells ◽

Type I ◽

Type Ii ◽

Muscle Satellite Cells ◽

Chicken Muscle ◽

Type I Igf Receptor ◽

Igf I ◽

Igf Receptor ◽

Insulin Like Growth Factors

ABSTRACT Insulin-like growth factors-I and -II (IGF-I and IGF-II) stimulate proliferation, differentiation, nutrient uptake and protein accretion in muscle cells. These effects are thought to be mediated through the type-I IGF receptor although a role for the type-II IGF receptor cannot be ruled out, since it has been found in most cells studied so far. Current evidence suggests that the chicken does not have a type-II IGF receptor and therefore provides a good model to study the function of IGF peptides. We have compared the effects of insulin and insulin-like growth factors on DNA synthesis with the binding of these peptides to receptors in primary chicken muscle satellite cells. Human IGF-I (hIGF-I), hIGF-II and porcine insulin increased thymidine incorporation into DNA by threefold in muscle satellite cells prepared from neonatal chickens. IGF-I and -II were almost equipotent, with half-maximum effective concentrations of 10 μg/l, and were 1000-fold more potent than insulin. A combination of maximum effective concentrations of all three peptides was not additive, suggesting that their effect was mediated by the same receptor. Receptor binding studies on satellite cells demonstrated the presence of specific IGF receptors. Human IGF-I inhibited the binding of 125I-labelled hIGF-I with a much higher potency than insulin, as usually observed for a type-I IGF receptor. However, unlabelled hIGF-II exhibited a higher potency than hIGF-I in displacing 125I-labelled hIGF-I. Affinity cross-linking of 125I-labelled hIGF-I and -II, followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, showed that hIGF-I and -II bound to a receptor with the structural characteristics of a type-I IGF receptor and confirmed the lack of a type-II IGF receptor in these cells. The concentrations of IGF-I, -II and insulin required for biological action and to displace 125I-labelled hIGF-I binding were similar, and support the hypothesis that their effects on proliferation were mediated exclusively through a type-I IGF receptor. Journal of Endocrinology (1991) 128, 35–42

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An evaluation of the role of insulin-like growth factors (IGF) and of type-I IGF receptor signalling in hepatocarcinogenesis and in the resistance of hepatocarcinoma cells against drug-induced apoptosis

Biochemical Pharmacology ◽

10.1016/j.bcp.2004.05.029 ◽

2004 ◽

Vol 68 (6) ◽

pp. 1003-1015 ◽

Cited By ~ 127

Author(s):

Catherine Alexia ◽

Guillaume Fallot ◽

Malika Lasfer ◽

Ghislaine Schweizer-Groyer ◽

André Groyer

Keyword(s):

Growth Factors ◽

Type I ◽

Drug Induced ◽

Receptor Signalling ◽

Type I Igf Receptor ◽

Hepatocarcinoma Cells ◽

Igf Receptor ◽

Induced Apoptosis ◽

Insulin Like Growth Factors

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The Role of Insulin-Like Growth Factors in Granulosa Cell Steroidogenesis: Studies with a Neutralizing Antibody to IGF-I

Growth Factors and the Ovary ◽

10.1007/978-1-4684-5688-2_15 ◽

1989 ◽

pp. 175-180

Author(s):

J. S. Mondschein ◽

S. F. Canning ◽

J. M. Hammond

Keyword(s):

Growth Factors ◽

Granulosa Cell ◽

Neutralizing Antibody ◽

Igf I ◽

Insulin Like Growth Factors

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Insulin-like growth factor receptors in chicken liver membranes: binding properties, specificity, developmental pattern and evidence for a single receptor type

Journal of Endocrinology ◽

10.1677/joe.0.1250199 ◽

1990 ◽

Vol 125 (2) ◽

pp. 199-206 ◽

Cited By ~ 33

Author(s):

M. J. Duclos ◽

C. Goddard

Keyword(s):

Growth Factors ◽

Rapid Growth ◽

Chicken Liver ◽

Affinity Constant ◽

Type I ◽

Liver Growth ◽

Α Subunit ◽

Single Receptor ◽

Igf I ◽

Insulin Like Growth Factors

ABSTRACT Two distinct receptors for the insulin-like growth factors (IGF-I and IGF-II) have been identified in mammalian tissues, but so far only a receptor structurally related to the type I receptor has been identified in chicken embryonic tissues. This study was designed to characterize binding sites for IGF peptides in chicken liver microsomal membranes prepared from hatch to 10 weeks of age which is the period of most rapid growth. Binding of both human (h) IGF-I and hIGF-II was displaceable by either peptide and exhibited similar pH, time and temperature dependency. Human IGF-II was more potent than hIGF-I in competing for the binding of the iodinated ligands with half-maximum effective concentrations of 3–5 μg/l and 7–13 μg/l respectively. Porcine insulin was also a potent competitor. Affinity cross-linking studies, followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis under reducing conditions demonstrated that both IGF peptides were linked to a protein with a molecular weight of about 130 000 Da characteristic of the α-subunit of the type I receptor. There was no evidence for the presence of a type II receptor similar to that found in mammals. Specific binding of both peptides was low on the day of hatch, increased about threefold by day 3 of age and remained high for the first 3 weeks of life before returning to a lower steady state level up to 10 weeks of age. This was the result of variation in receptor number, with no change in the affinity of the binding site for either ligand. The affinity constant for IGF-II (4·5 ± 0·5 (s.e.m.) litres/nmol) was higher than for IGF-I (1·4 ± 0·3 litres/nmol). Insulin-like growth factors have previously been reported to stimulate the metabolism and growth of hepatocytes in vitro and are produced by these cells. The occurrence of a higher number of receptors at the period of most rapid growth of the liver suggests that they may have a role in regulating normal liver growth in an autocrine or paracrine manner. Furthermore, present evidence suggests that this is through a single receptor related to the type I receptor. Journal of Endocrinology (1990) 125, 199–206

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Effects of gonadotropins and insulin-like growth factors-I and -II on in vitro steroid production by bovine granulosa cells

Canadian Journal of Animal Science ◽

10.4141/a98-005 ◽

1998 ◽

Vol 78 (4) ◽

pp. 587-597 ◽

Cited By ~ 12

Author(s):

M. Y. Yang ◽

R. Rajamahendran

Keyword(s):

Growth Factors ◽

Granulosa Cells ◽

Culture System ◽

Physiological Role ◽

Serum Free ◽

Igf I ◽

The Media ◽

Estradiol 17Β ◽

Insulin Like Growth Factors

The objectives of this study were: 1) to develop a bovine granulosa cell (GC) culture system; and 2) to use this system to evaluate the effects of gonadotropins (FSH and LH) and insulin-like growth factors-I and -II (IGF-I and IGF-II) on steroidogenesis of bovine GC derived from small, medium, and large antral follicles (diameters ≤4, 5–8 and >8 mm, respectively). Granulosa cells were cultured (concentration, 5 × 105 cells per well) in serum-free medium for 48 h with variable doses of hormones and growth factors. Concentrations of progesterone (P4) and estradiol-17β (E2) in the media were determined by radioimmunoassay. Basal E2 production by GC from follicles of all sizes decreased with time of culture (P < 0.01) while basal P4 production increased (P < 0.01). Basal E2 and P4 production increased with increasing size of follicles (P < 0.01). Only very low concentrations of FSH stimulated E2 production from medium and large follicles. Follicle-stimulating hormone stimulated P4 production by GC of follicles of all sizes (P < 0.05). Luteinizing hormone inhibited E2 production by GC in medium and large follicles (P < 0.05), suggesting that LH is responsible for the rise in plasma E2 through effects on both theca cells and GC. A dose of 100 ng mL−1 of IGF-I increased E2 production by GC from medium and large follicles (P < 0.05). Progesterone production by GC from all categories of follicles was also stimulated by IGF-I (P < 0.05). Estradiol-17β production by GC from large follicles decreased in response to IGF-II (P < 0.05). The physiological role of IGF-II on steroidogenesis in the bovine ovary remains to be elucidated. In summary, these results demonstrate the development of a serum-free culture system for bovine GC, and that FSH, LH, IGF-I and IGF-II have different effects on steroidogenesis by bovine GC from different size follicles. Key words: Granulosa cells, gonadotropins, Insulin-like growth factors, progesterone, estradiol-17β, cows

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Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor and IGF-binding protein-2 mRNA and peptide levels in normal and nephrectomized rat kidney

Kidney International ◽

10.1038/ki.1995.442 ◽

1995 ◽

Vol 48 (5) ◽

pp. 1517-1529 ◽

Cited By ~ 22

Author(s):

Andrew P. Evan ◽

David P. Henry ◽

Bret A. Connors ◽

Patricia Summerlin ◽

Wei-Hua Lee

Keyword(s):

Growth Factors ◽

Binding Protein ◽

Rat Kidney ◽

Type Ii ◽

Igf I ◽

Igf Binding ◽

Igf Receptor ◽

Igf Binding Protein ◽

Insulin Like Growth Factors

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Effects of growth factors and hormones on basal and FSH-stimulated inhibin production by porcine granulosa cells in vitro

Reproduction Fertility and Development ◽

10.1071/rd9910201 ◽

1991 ◽

Vol 3 (2) ◽

pp. 201 ◽

Cited By ~ 5

Author(s):

U Michel ◽

S Ludemann ◽

H Jarry ◽

W Wuttke

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Granulosa Cells ◽

Type I ◽

Tgf Beta ◽

G Cells ◽

Porcine Granulosa Cells ◽

Igf I ◽

Factor Type

The effect of several growth factors, protein and steroid hormones on follicle stimulating hormone (FSH)-stimulated and basal inhibin secretion by mature porcine granulosa cells (g-cells) in culture was examined in order to elucidate the putative role of growth factors and hormones in the regulation of inhibin secretion by porcine g-cells in vitro. Cells were incubated with the respective hormones over a timespan of 0-144 h and immunoreactive inhibin was measured with a radioimmunoassay against porcine inhibin. Epidermal growth factor (EGF) and human transforming growth factor type beta (TGF-beta) decreased basal and gonadotrophin-stimulated inhibin and progesterone in a dose-dependent manner. In the absence of insulin, insulin-like growth factor type I (IGF-I) caused a 4-fold enhancement of basal inhibin secretion, but inhibin secretion was elevated only to 20% above control in the presence of 500 nM insulin. Porcine platelet-derived growth factor (PDGF) had no significant effect on basal or FSH-induced inhibin secretion by g-cells. In addition, neither gonadotrophin-releasing hormone (GnRH) nor prolactin (PRL), arginine vasopressin (AVP) and oxytocin affected basal or FSH-stimulated inhibin release by porcine g-cells. Oestradiol caused a slight but significant (P less than 0.01) rise of basal inhibin production (158% of control) in the last 2 days of culture (96-144 h) and the effect of androstenedione on basal (158% of control) and FSH-stimulated (140% of control) inhibin release (P less than 0.01) was also only visible on Days 4-6 of culture. In contrast to androstenedione and oestradiol, progesterone did not show any effect during 6 days of culture in a dose range of 10(-5) to 10(-9) M. Like steroids, prostaglandin E2 (PGE2) had a stimulatory effect on basal inhibin production (250% of control) by porcine g-cells, visible on Days 3-6 of culture, but an inhibitory effect on FSH-stimulated release (less than 40% of control). Over all the experiments with different hormones and growth factors, tested in varying doses and over a time span of 0-144 h, there was a strong correlation between progesterone and inhibin secretion by g-cells (0-48 h = 0.78; 48-96 h = 0.92; 96-144 h = 0.92). These results suggest that EGF, TGF-beta, IGF-I, oestradiol and androstendione as well as PGE2 have para- and/or autocrine modulatory effects on basal and FSH-stimulated inhibin secretion by mature porcine g-cells in vitro and further demonstrate that the secretion of the proteohormone inhibin and the steroid progesterone are closely related.

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