Insulin-like growth factors-I and -II and insulin-like growth factor-binding protein-2 in dominant equine follicles during spring transition and the ovulatory season

The period between seasonal anoestrus and cyclicity is characterized in many mares by cyclical growth and regression of large dominant follicles. The insulin-like growth factor (IGF) system plays a key role in follicular growth and regression; therefore, we hypothesized that changes in the IGF system and its binding proteins would modulate onset of cyclicity in mares. Ovaries were obtained from pony mares on the day after detection of an actively growing 30 mm transitional anovulatory follicle, and also at the second or third oestrus of the breeding season on the day after the preovulatory follicle reached 30 mm in diameter. Size of dominant follicles at the time of removal was similar in transition (32 ± 0.8 mm) and at oestrus (34 ± 0.6 mm). IGF-I mRNA was present in granulosa cells, with low thecal expression, whereas IGF-II mRNA was confined to the theca layer. Expression of IGF-I and -II mRNAs, and intrafollicular concentrations of oestradiol, were lower (P < 0.01; paired t test) in transitional anovulatory follicles than in preovulatory follicles. Messenger RNA encoding IGFBP-2 was present in both theca and granulosa layers. Steady-state concentrations of mRNA encoding IGFBP-2 mRNA increased (P < 0.001) in theca in preovulatory follicles. Intrafollicular concentrations of IGFBP-2 were higher (P < 0.001) in transitional than in preovulatory follicles. The similarity in circulating concentrations of IGF-I in transitional and cyclic mares, suggested that the somatotrophic axis is not involved in transition from anovulatory to ovulatory cycles. The results suggest that the increased expression of IGF-I and -II mRNAs in preovulatory follicles, along with the decrease in IGFBP-2 concentrations, could increase the bioavailability of intrafollicular IGF in large follicles during the breeding season, and support our hypothesis that intrafollicular IGF bioavailability must exceed a threshold level before ovulation can occur.

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IGF-binding protein-2 is induced during development of urinary bladder hypertrophy in the diabetic rat

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.272.2.e297 ◽

1997 ◽

Vol 272 (2) ◽

pp. E297-E303 ◽

Cited By ~ 4

Author(s):

Y. Chen ◽

B. Gustafsson ◽

H. J. Arnqvist

Keyword(s):

Growth Factor ◽

Urinary Bladder ◽

Messenger Rna ◽

Diabetic Rat ◽

Insulin Like Growth Factor ◽

Igf System ◽

Igf I ◽

Igf Binding ◽

Streptozotocin Induced Diabetes ◽

Wet Weight

Because the locally produced insulin-like growth factor-binding proteins (IGFBP) may influence bladder hypertrophy, either directly or by their interaction with insulin-like growth factor I (IGF-I), we studied the IGF system during the development of urinary bladder hypertrophy in rats with streptozotocin-induced diabetes. Messenger RNA for IGF-I, IGFBP-2, and IGFBP-4 was determined by solution hybridization. The bladder wet weight was elevated after 7 days. DNA synthesis was increased and peaked at 2 days, whereas DNA content per bladder wet weight was decreased by 7 days. The IGF-I mRNA did not change during the first 7 days and then decreased, and IGFBP-4 mRNA was increased transiently on day 7. On the other hand, IGFBP-2 mRNA was significantly increased after 1 day (2-fold), peaked by 7 days (6.4-fold), and then declined to approximately 50% above control at the end of experiment. This was associated with an increased IGFBP-2 protein content. Our results suggest that both stretching of the bladder due to diuresis and the diabetic state contribute to changes of the IGF system in the hypertrophying bladder.

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Physical capacity influences the response of insulin-like growth factor and its binding proteins to training

Journal of Applied Physiology ◽

10.1152/japplphysiol.00145.2002 ◽

2002 ◽

Vol 93 (5) ◽

pp. 1669-1675 ◽

Cited By ~ 62

Author(s):

Lars Rosendal ◽

Henning Langberg ◽

Allan Flyvbjerg ◽

Jan Frystyk ◽

Hans Ørskov ◽

...

Keyword(s):

Growth Factor ◽

Physical Training ◽

Binding Proteins ◽

Insulin Like Growth Factor ◽

Initial Training ◽

Serum Samples ◽

Fitness Level ◽

Igf System ◽

Igf I ◽

Igfbp 3

The influence of initial training status on the response of circulating insulin-like growth factor (IGF) and its binding proteins (IGFBP) to prolonged physical training was studied in young men. It was hypothesized that highly standardized training would result in more extensive changes in the circulating IGF system in untrained subjects because of lower fitness level. Seven untrained (UT) and 12 well-trained (WT) individuals performed 11 wk of intense physical training (2–4 h daily). Fasting serum samples were analyzed for total and free IGF-I and -II, for IGFBP-1 to -4, as well as for IGFBP-3 proteolysis. Eleven weeks of physical training resulted in decreased levels of total IGF-I, free IGF-I, and IGFBP-4 in both the UT and WT groups. In the UT group, IGFBP-2 increased, IGFBP-3 decreased [from 4,255 ± 410 (baseline) to 3,896 ± 465 (SD) μg/l ( week 4); P < 0.05], and IGFBP-3 proteolysis increased [from 28 ± 8% (baseline) to 37 ± 7% ( week 4) and 39 ± 12% ( week 11); P < 0.05], whereas no significant changes were found in the WT group. In conclusion, intense physical training results in a marked influence on the IGF system and its binding proteins with generally more extensive changes seen in the untrained individuals. Also, prolonged physical training resulted in increased IGFBP-3 proteolysis in previously untrained individuals only, indicating that intense physical training affects trained and untrained individuals differently.

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The Effect of Oral Glucose on Serum Free Insulin-Like Growth Factor-I and -II in Healthy Adults*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.9.4259 ◽

1997 ◽

Vol 82 (9) ◽

pp. 3124-3127 ◽

Cited By ~ 1

Author(s):

Jan Frystyk ◽

Thorbjørn Grøfte ◽

Christian Skjærbæk ◽

Hans Ørskov

Keyword(s):

Growth Factor ◽

Healthy Subjects ◽

Time Course ◽

Oral Glucose ◽

Insulin Like Growth Factor ◽

Serum Samples ◽

Cross Sectional ◽

Igf System ◽

Igf I ◽

The Impact

Abstract Insulin-like growth factor (IGF) binding protein-I (IGFBP-1) has been suggested to regulate the availability of free IGF and the glucose lowering activity of the IGF-system in relation to fuel supply. Our recent observations of significant inverse correlations between free IGF-I and IGFBP-1 in cross-sectionally collected fasting serum samples support a possible physiological association between the peptides. To further study the impact of IGFBP-1 on free IGF levels and the possible participation of the IGF-system in glucose homeostasis, we studied the time course of changes in IGFBP-1 and free IGFs in 13 healthy subjects undergoing an oral glucose tolerance test (OGTT). Serum was collected every 30 min for 330 min. Glucose, insulin, and GH followed the expected patterns and had regained baseline levels at 270 min. Total IGF-I and free and total IGF-II remained unaltered. IGFBP-1 decreased significantly by 37–52% (P < 0.05) from 150 to 210 min, whereafter the concentration gradually increased by 75% to a level that tended to be above baseline (P = 0.052). Free IGF-I decreased by 29–38% (P < 0.05) at the end of the study (270–330 min). IGFBP-1 was inversely correlated to free IGF-I at baseline (r = −0.57; P < 0.05), as well as during the OGTT (r = 0.66; P < 0.0001). In contrast, free IGF-II was not correlated to IGFBP-1. Insulin, but not free IGF-I, correlated significantly with serum glucose (P < 0.05). These results extend our previous findings of an inverse correlation between free IGF-I and IGFBP-1 in cross-sectional studies to include longitudinal observations, and thus further substantiates the hypothesis that IGFBP-1 is an important determinant of free IGF-I in vivo. Significant changes in free IGF-I were observed only in the late postprandial phase, when glucose and insulin were fully normalized, demonstrating that free IGFs probably do not participate in glucoregulation to any significant degree during an oral glucose load in healthy subjects.

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Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake

Public Health Nutrition ◽

10.1079/phn2005729 ◽

2005 ◽

Vol 8 (6) ◽

pp. 620-627 ◽

Cited By ~ 27

Author(s):

AH Heald ◽

R Sharma ◽

SG Anderson ◽

A Vyas ◽

K Siddals ◽

...

Keyword(s):

Growth Factor ◽

Dietary Intake ◽

Total Energy ◽

Macronutrient Intake ◽

Fat Intake ◽

Insulin Like Growth Factor ◽

Igf System ◽

Igf I ◽

Total Fat ◽

Igfbp 3

AbstractBackgroundThe insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease.ObjectiveWe report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate.Design, subjects and settingDietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n = 205) compared with people still resident in the same villages of origin in India (n = 246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured.ResultsTotal energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1–153.6) vs. 100.9 (94.6–107.3) ng ml-1; F = 76.6, P < 0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9–33.0) vs. 56.5 (50.6–62.5) μg l-1; F = 48.4, P < 0.001). At both sites, IGF-I correlated positively with total energy (Spearman's ρ = 0.45, P < 0.001) and total fat (ρ = 0.44, P < 0.001) as did IGFBP-3 with total energy (ρ = 0.21, P < 0.05) and fat (ρ = 0.26, P < 0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (ρ = -0.27, P < 0.001) and fat intake (ρ = -0.26, P < 0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (β = 0.42, P = 0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose.ConclusionIn these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.

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Expression of the insulin-like growth factor system in the hypokalemic rat kidney

AJP Renal Physiology ◽

10.1152/ajprenal.1997.272.5.f661 ◽

1997 ◽

Vol 272 (5) ◽

pp. F661-F667 ◽

Cited By ~ 3

Author(s):

R. M. Rohan ◽

T. G. Unterman ◽

L. Liu ◽

M. K. Hise

Keyword(s):

Growth Factor ◽

Binding Protein ◽

Collecting Duct ◽

Rat Kidney ◽

Insulin Like Growth Factor ◽

Distal Nephron ◽

Igf System ◽

Igf I ◽

Igf Binding ◽

Igf Binding Protein

We studied the renal expression of the insulin-like growth factor (IGF) system to gain a better perspective of its potential role in the hyperplastic adaptation of the distal nephron to potassium deficiency. Rats were pair fed 1% or 0.002% potassium diets for periods up to 10 days. IGF-I mRNA was diminished in potassium-deficient rats within 4 days, whereas mRNA for IGF binding protein-1 (IGFBP-1), a collecting duct-associated protein, was increased by day 7. At day 10 mRNA for IGFBP-1 in potassium-deficient animals averaged 2.07 +/- 0.53 (mean +/- SD, relative densitometry units) compared with 0.89 +/- 0.26 in control rats (n = 4, P = 0.002). Conversely, IGFBP-3, a binding protein whose mRNA has been localized to the interstitial compartment, averaged 2.40 +/- 0.02 in potassium-deficient rats and 4.77 +/- 0.05 in controls (n = 4, P < 0.03) at day 10 of treatment. Immunohistochemistry performed using a specific IGFBP-1 antibody revealed hyperplasia of distal nephron segments along with an increase in IGFBP-1 in potassium-depleted rats. These data suggest that IGFBP-1 may play an important role in the control of cellular adaptations in the hypokalemic rat kidney either directly by influencing cell migration or indirectly by localizing IGF-I to the distal nephron.

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Growth hormone induction of insulin-like growth factor I messenger RNA in primary cultures of rat liver cells

Journal of Endocrinology ◽

10.1677/joe.0.1150135 ◽

1987 ◽

Vol 115 (1) ◽

pp. 135-139 ◽

Cited By ~ 30

Author(s):

G. Norstedt ◽

C. Möller

Keyword(s):

Growth Factor ◽

Hormonal Regulation ◽

Messenger Rna ◽

Primary Cultures ◽

Liver Cells ◽

Insulin Like Growth Factor ◽

Adult Rats ◽

Factor I ◽

Igf I ◽

Growth Factor I

ABSTRACT Primary liver cells from adult rats were used to study the hormonal regulation of mRNA coding for insulin-like growth factor I (IGF-I). IGF-I mRNA could be detected at a low concentration in liver cells prepared from hypophysectomized rats and cultivated for 3 days. When these cells were exposed to GH on the second day, a dose-dependent increase in IGF-I mRNA was observed. The continuous presence of serum was not a prerequisite for this response, since GH also induced IGF-I mRNA in a defined hormone-supplemented medium. It is concluded that GH can induce IGF-I mRNA in the liver by a direct mechanism. J. Endocr. (1987) 115, 135–139

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Effect of a high maternal dietary intake during mid-gestation on components of the utero-placental insulin-like growth factor (IGF) system in adolescent sheep with retarded placental development

Reproduction ◽

10.1530/reprod/118.2.407 ◽

2000 ◽

pp. 407-416 ◽

Cited By ~ 11

Author(s):

TS Gadd ◽

RP Aitken ◽

JM Wallace ◽

DC Wathes

Keyword(s):

Growth Factor ◽

Mrna Expression ◽

Maternal Nutrition ◽

Limit Of Detection ◽

Receptor Expression ◽

Insulin Like Growth Factor ◽

Placental Development ◽

Igf System ◽

Igf I ◽

Igfbp 3

The aim of the present study was to investigate the effects of administering a high plane diet during early to mid-gestation on the uterine and placental insulin-like growth factor (IGF) system and on systemic IGF-I concentrations in pregnant adolescent ewes with restricted placental growth. Embryos recovered from superovulated ewes inseminated by a single sire were transferred in singleton to the uterus of adolescent recipients. After transfer ewes were offered a high (H) or moderate (M) amount of a complete diet calculated to promote rapid or normal maternal growth rates, respectively. Five ewes from each group were switched from either M to H or H to M diets at day 52 of gestation. Maternal and fetal blood samples and placental tissues were collected from all animals at day 104. Ewes on the high plane diet from mid-gestation (HH, MH groups) had restricted placental mass (P < 0.01) and tended to have smaller fetuses. This was associated with increased maternal plasma IGF-I concentrations (P < 0.001). The pattern of expression of components of the IGF system in the uterus and placenta was studied by in situ hybridization. IGF-I mRNA concentrations were below the limit of detection. IGF-II mRNA expression was high in the fetal mesoderm and present in maternal stroma, but was not influenced by nutritional treatment. In contrast, IGF binding protein 1 (IGFBP-1) mRNA expression was higher (P < 0.05) and IGFBP-3 mRNA expression was lower (P < 0.05) in the endometrial glands of ewes in HH and MH groups. In the fetal trophoblast, IGFBP-3 mRNA expression was higher in the MH group. Type 1 IGF receptor expression was increased (P < 0. 01) in the luminal epithelium of the HM group and IGFBP-2 mRNA expression was highest in the placentome capsule of ewes in the HH group. Together, these results indicate that reprogramming of the uterine and placental IGF axis by maternal nutrition could contribute to placental growth retardation in growing adolescent sheep.

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Electroacupuncture Promotes Insulin-Like Growth Factors System in Ovariectomized Osteoporosis Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x08006326 ◽

2008 ◽

Vol 36 (05) ◽

pp. 889-897 ◽

Cited By ~ 18

Author(s):

Yi Feng ◽

Huagang Lin ◽

Ying Zhang ◽

Lierong Li ◽

Xuping Wu ◽

...

Keyword(s):

Growth Factor ◽

Bone Mineral ◽

Sham Operation ◽

Insulin Like Growth Factor ◽

Mineral Density ◽

Thigh Bone ◽

Igf System ◽

Significant Difference ◽

Igf I

Postmenopausal Osteoporosis (PMOP) is induced by the deficiency of estrogen in postmenopausal women. Electroacupuncture (EA) has been confirmed to be effective in clinic. We adopted ovariectomized osteoporosis model of rats to observe the role of EA in PMOP. Fifty female SD rats were divided randomly into 5 groups: intact (INT, n = 10), sham operation (Sham, n = 10), model ( n = 10), estrogen (E, n = 10) and electroacupuncture (EA, n = 10). The bone mineral content (BMC) and the bone mineral density (BMD) were examined in lumbar1–6 and right thigh-bone, respectively, and estrodiol (E2), insulin-like growth factor I (IGF-I) and insulin-like growth factor binding proteins (IGF-BPs) were tested by RIA or ELISA. The results showed that BMC and BMD of lumbar 1–6 and right thigh-bone in PMOP model rats decreased markedly, while the level of serum E2, IGF-I and IGF-BP1 were lower than in INT and Sham. However, EA could upgrade the contents of IGF-I and IGF-BP1 to increase BMD in PMOP rats, while no significant difference was seen in E group. Therefore, EA may promote IGF system to improve PMOP.

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