scholarly journals Effects of decreased estradiol-17β on the serum and anterior pituitary IGF-I system in pigs

2005 ◽  
Vol 187 (3) ◽  
pp. 369-378 ◽  
Author(s):  
C K Hilleson-Gayne ◽  
J A Clapper
Keyword(s):  
Anterior Pituitary ◽  
Percentage Increase ◽  
Serum Concentrations ◽  
Blood Samples ◽  
Treatment Groups ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Estradiol 17Β

To further delineate the role of estradiol in the IGF system an experiment was conducted to determine the dosage of the aromatase inhibitor, anastrozole, needed to decreases serum concentrations of estradiol-17β (E2) in maturing boars. A second experiment was conducted to determine if administration of anastrozole to growing boars decreased serum concentrations of E2 and affected components of the serum and anterior pituitary gland (AP) IGF system vs untreated boars and barrows. In Experiment 1, 12 crossbred boars (292 days, 158 kg) were administered either 0, 1 or 10 mg/day anastrozole (n=4/group) beginning on day 1. Blood samples were collected every 7–14 days. Mean serum concentrations of E2 were decreased (P < 0·05) in the 10 mg group vs the 0 and 1 mg groups by day 36; however, no difference (P > 0·05) existed between the 0 and 1 mg groups. In Experiment 2, 24 crossbred boars and 12 barrows (101 days, 44 kg) were stratified by litter to one of three treatment groups (n=12): boars administered 10 mg/day anastrozole, boars administered 0 mg/day, and barrows administered 0 mg/day. Blood samples were collected and pigs were weighed on day 0 and every 14 days thereafter, then killed on day 84 when blood and APs were collected. The 10 mg/day pigs were fed the anastrozole-amended diet beginning on day 1. Mean serum concentrations of E2 did not differ (P > 0·05) between the 10 mg/day pigs and 0 mg/day pigs on day 0; however, on day 15 through to 84 mean serum concentrations of E2 were greater (P < 0·05) in 0 mg/day pigs than in the 10 mg/day pigs. Mean percentage increase in serum concentrations of IGF-I was greater (P < 0·05) in untreated boars than anastrozole-treated boars and barrows from day 58 through to 84. Mean percentage of basal IGF-I increased (P < 0·05) from day 29 through to 84 in untreated boars. Mean relative amounts of AP IGF-binding protein (IGFBP)-2 and -5 were less (P < 0·01) in 10 mg/day pigs than in the 0 mg/day pigs, but each was greater (P < 0·01) than in barrows administered 0 mg/day. These results indicate anastrozole administered at a dosage of 10 mg/day suppresses serum concentrations of E2 in pigs. Administration of anastrozole to boars reduced the percentage increase in serum concentrations of IGF-I and relative amounts of AP IGFBP-2 and -5. These data further support a role for E2 in regulating components of the IGF system in pigs.

scholarly journals Dexamethasone administration attenuates the inhibitory effect of lipopolysaccharide on IGF-I and IGF-binding protein-3 in adult rats

2005 ◽  
Vol 185 (3) ◽  
pp. 467-476 ◽  
Author(s):  
Teresa Priego ◽  
Miriam Granado ◽  
Ana Isabel Martín ◽  
Asunción López-Calderón ◽  
María Angeles Villanúa
Keyword(s):  
Gene Expression ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Serum Concentrations ◽  
Gh Receptor ◽  
Its Gene ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

The aim of this study was to investigate whether glucocorticoid administration had a beneficial effect on serum concentrations of insulin-like growth factor I (IGF-I) and on IGF-binding protein 3 (IGFBP-3) in rats injected with lipopolysaccharide (LPS). Adult male rats were injected with LPS or saline and pretreated with dexamethasone or saline. Dexamethasone administration decreased growth hormone (GH) receptor and IGF-I mRNA levels in the liver of control rats. LPS decreased GH receptor and IGF-I gene expression in the liver of saline-treated rats but not in the liver of dexamethasone-pretreated rats. In the kidney, GH receptor mRNA levels were not modified by dexamethasone or LPS treatment. However, LPS decreased renal IGF-I gene expression and dexamethasone pretreatment prevented this decrease. Serum concentrations of IGF-I were decreased by LPS, and dexamethasone pretreatment attenuated this effect. The gene expression of IGFBP-3 in the liver and kidney and its circulating levels were decreased by LPS. In control rats dexamethasone increased circulating IGFBP-3 and its gene expression in the liver, and decreased the proteolysis of this protein. Dexamethasone pretreatment attenuated the LPS-induced decrease in IGFBP-3 gene expression in the liver and prevented the LPS-induced decrease in IGFBP-3 gene expression in the kidney. Moreover, dexamethasone pretreatment attenuated the LPS-induced decrease in serum concentrations of IGFBP-3 and decreased the LPS-induced IGFBP-3 proteolysis in serum. In conclusion, dexamethasone pretreatment partially attenuates the inhibitory effect of LPS on serum IGF-I by blocking the decrease of its gene expression in the kidney as well as by attenuating the decrease in serum concentrations of IGFBP-3.

The effects of insulin-like growth factor-I (IGF-I), IGF-II and des(1–3)IGF-I, a potent IGF analogue, on growth hormone and IGF-binding protein secretion from cultured rat anterior pituitary cells

1991 ◽  
Vol 130 (1) ◽  
pp. 93-99 ◽  
Author(s):  
J. M. Simes ◽  
J. C. Wallace ◽  
P. E. Walton
Keyword(s):  
Growth Factor ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Gh Secretion ◽  
Factor I ◽  
Anterior Pituitary Cells ◽  
Low Concentrations ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein

ABSTRACT The effects of insulin-like growth factor-I (IGF-I), IGF-II and des(1–3)IGF-I, a potent IGF-I analogue, on the secretion of GH and IGF-binding protein (IGFBP) from cultured rat anterior pituitary cells were measured. IGF-I and des(1–3)IGF-I stimulated GH secretion at low concentrations (maximally effective at 1 and 0·1 μg/l respectively) and inhibited GH secretion at higher concentrations. The half-maximal inhibitory concentrations (IC50) were approximately 20 μg/l and 1 μg/l for IGF-I and des(1–3)IGF-I respectively. Thus des(1–3)IGF-I was more potent than IGF-I in these effects on GH secretion. We postulate that the increased potency of des(1–3)IGF-I in affecting GH secretion is due to decreased binding of this peptide by pituitary IGFBP compared with IGF-I. In contrast with IGF-I and des(1–3)IGF-I, IGF-II did not stimulate GH secretion at low concentrations, but did inhibit GH secretion from pituitary cells with an IC50 of approximately 20 μg/l. Several IGFBPs ranging in molecular mass from 22 000 to 52 000 were detected in medium conditioned by cultured anterior pituitary cells. When measured by Western-ligand blotting and competitive ligand-binding techniques, these IGFBPs exhibited decreased binding of des(1–3)IGF-I compared with IGF-I and IGF-II. The production of IGFBP by anterior pituitary cells was stimulated by the addition of IGFs to the culture medium. Journal of Endocrinology (1991) 130, 93–99

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

1997 ◽  
Vol 272 (5) ◽  
pp. F661-F667 ◽  
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.

scholarly journals Associations of serum carotenoid concentrations and fruit or vegetable consumption with serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 concentrations in the Third National Health and Nutrition Examination Survey (NHANES III)

2016 ◽  
Vol 5 ◽  
Author(s):  
Anja Diener ◽  
Sabine Rohrmann
Keyword(s):  
Fruits And Vegetables ◽  
Molar Ratio ◽  
Nhanes Iii ◽  
Serum Concentrations ◽  
Health And Nutrition ◽  
Igf System ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Β Carotene ◽  
Igfbp 3

AbstractDietary intervention may alter the insulin-like growth factor (IGF) system and thereby cancer risk. In a qualitative review, eleven of twenty studies showed a link between one or more carotenoids, vegetable or fruit intake and the IGF system, however, with partly contrary findings, such that no firm conclusion can be drawn. Therefore, we evaluated associations between serum carotenoid concentrations or the intake of fruits and vegetables with IGF-1, IGF binding protein (BP)-3 and their molar ratio (IGF-1:IGFBP-3) within the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994). In our analysis, we included 6061 NHANES III participants and used multivariable-adjusted linear regression models. IGF-1 concentrations were significantly positively associated with serum concentrations of lycopene, β-carotene, α-carotene, β-cryptoxanthin and lutein/zeaxanthin in men and women. Statistically significant positive associations were observed for serum concentrations of α-carotene and lutein/zeaxanthin and intake of fruits with serum IGFBP-3 concentrations in women, but not in men. The IGF-1:IGFBP-3 molar ratio was significantly positively associated with serum concentrations of lycopene, β-carotene and α-carotene in men and with β-carotene in women. In conclusion, dietary interventions with carotenoids, fruits and vegetables may affect the IGF system, although the direction of these effects is currently unclear.

scholarly journals Increased Insulin-Like Growth Factor (IGF)-II and IGF/IGF-Binding Protein Ratio in Prepubertal Constitutionally Tall Children

2002 ◽  
Vol 87 (12) ◽  
pp. 5455-5460 ◽  
Author(s):  
S. Garrone ◽  
G. Radetti ◽  
M. Sidoti ◽  
M. Bozzola ◽  
F. Minuto ◽  
...  
Keyword(s):  
Growth Velocity ◽  
Binding Protein ◽  
Molar Ratio ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Acid Labile Subunit ◽  
Igf Binding Protein ◽  
Acid Labile ◽  
Igfbp 3

Abstract The height of subjects with constitutionally tall stature (CTS) is at least 2 sd above the mean of subjects of the same age and sex. Apart from a few discordant data on the role of GH and its direct mediator, IGF-I, no studies have been conducted on other components of the IGF system, which also condition the bioavailability and activity of IGF-I. We, therefore, investigated the possibility that other components of the IGF system might play a role in determining the increased growth velocity seen in CTS. To this end, we evaluated the behavior not only of IGF-I but also of IGF-II, IGF-binding protein (IGFBP)-3, and acid-labile subunit, the subunits that constitute the main IGF complex in circulation (150-kDa complex), as well as of IGFBP-1 and IGFBP-2, which are negatively regulated by GH and, like IGFBP-3, able to influence the bioavailability of the IGFs. The study was performed on 22 prepubertal subjects affected by CTS (16 males and 6 females), aged 2.8–13.3 yr (6.8 ± 0.5 yr, mean ± sem). Thirty-seven normal prepubertal subjects (16 males and 21 females) aged between 2.2 and 13.3 yr (6.7 ± 0.5 yr), who were comparable in socioeconomic and nutritional terms, served as controls. From the auxological point of view, subjects with CTS differed significantly from controls only in terms of growth velocity (HV-sd score; CTS, 1.8 ± 0.3; controls, 0.4 ± 0.2; P &lt; 0.0001) and height (H-sd score; CTS, 3.1 ± 0.1; controls, 0.4 ± 0.2; P &lt; 0.0001). The results demonstrated that the concentrations of IGF-I (27.3 ± 2.0 nmol/liter), IGFBP-3 (66.9 ± 3.8), and acid-labile subunit (216.8 ± 13.6) in CTS-affected subjects were not significantly different from those determined in controls (25.0 ± 2.9, 74.4 ± 4.1, and 241.0 ± 11.9, respectively). By contrast, IGF-II levels proved significantly higher in CTS subjects (IGF-II: 87.2 ± 3.4 vs. 52.4 ± 2.3, P &lt; 0.0001). Chromatographic analysis, performed after acid treatment of pooled sera, showed only the presence of normal 7.5-kDa IGF-II in both CTS subjects and controls. In comparison with controls, CTS children showed a lower concentration of IGFBP-1 (1.6 ± 0.3 vs. 4.1 ± 0.7, P = 0.03) and a higher concentration of IGFBP-2 (14.3 ± 1.8 vs. 9.6 ± 1.1, P = 0.03). The IGFs (IGF-I and -II)/IGFBPs (−1 + −2 + −3) molar ratio was significantly higher (P &lt; 0.0001) in CTS children than in controls. In particular, the IGF-II/IGFBP ratio (P &lt; 0.0001) was responsible for the excess of the IGF peptide in relation to the concentrations of IGFBPs and, therefore, for the increase in the potentially bioactive free form of the IGFs. Moreover, the IGFBP-3/IGF molar ratio was significantly reduced, being less than 1 in CTS subjects (0.6 ± 0.1 vs. 1.1 ± 0.1), so that a quantity of IGF peptides lack sufficient IGFBP-3 to form the 150-kDa complex with which are normally sequestered in the vascular compartment. The data show that in CTS: 1) the most GH-dependent components of the IGF system are normal, consistent with the finding of a normal GH secretory state; 2) the less GH-dependent IGF-II is significantly increased, in agreement with the finding of a relationship between high levels of IGF-II and overgrowth in some syndromes; and 3) the IGF/IGFBP molar ratio is increased, and, therefore, a greater availability of free IGF for target tissues may be responsible for overgrowth in CTS.

scholarly journals Follicle selection in cattle and horses: role of intrafollicular factors

Reproduction ◽  
2006 ◽  
Vol 132 (3) ◽  
pp. 365-377 ◽  
Author(s):  
M A Beg ◽  
O J Ginther
Keyword(s):  
The Other ◽  
Dominant Follicle ◽  
Follicular Wave ◽  
Igf System ◽  
Igf I ◽  
The Future ◽  
Igf Binding ◽  
Preparatory Stage ◽  
Igf Binding Protein ◽  
Follicle Selection

The eminent event in follicle selection during a follicular wave in monovular species is diameter deviation, wherein one follicle continues to grow (developing dominant) and other follicles (subordinates) begin to regress. In cattle, the IGF system, oestradiol and LH receptors are involved in the intrafollicular events initiating deviation as indicated by the following: (1) concentrations of free IGF-I and oestradiol in the follicular fluid and number of LH receptors in the follicular wall increase more dramatically in the future dominant follicle than in the future subordinate follicles before the beginning of deviation and (2) ablation of the largest follicle (LF) or injection of recombinant human IGF (rhIGF)-I into the second LF at the expected beginning of deviation increases the concentrations of oestradiol in second LF before the expected beginning of deviation between second LF and third LF. In horses, an increase in free IGF-I, oestradiol, inhibin-A and activin-A is greater in the future dominant follicle than in other follicles before the beginning of deviation. However, free IGF-I is the only one of these four factors needed for the initiation of deviation in horses as indicated by the following: (1) ablation of LF at the expected beginning of deviation increases the concentrations of free IGF-I in second LF before the beginning of deviation between second LF and third LF but does not increase the other factors; (2) injection of rhIGF-I into second LF at the expected beginning of deviation causes second LF to continue to grow and become a codominant follicle and (3) injection of IGF-binding protein-3 into LF at the expected beginning of deviation causes LF to regress and second LF to become dominant. Thus, the dramatic changes in the IGF system in LF compared to other follicles before the beginning of deviation play a crucial role in the events that lead to the beginning of diameter deviation in both cattle and horses. Oestradiol and LH receptors also play a role in cattle. These intrafollicular events prepare the selected follicle for the decreasing availability of FSH and increasing availability of LH. The other follicles of the wave have the same future capability but do not have adequate time to attain a similar preparatory stage.

scholarly journals Lack of Dietary Carbohydrates Induces Hepatic Growth Hormone (GH) Resistance in Rats

Endocrinology ◽  
2011 ◽  
Vol 152 (5) ◽  
pp. 1948-1960 ◽  
Author(s):  
Maximilian Bielohuby ◽  
Mandy Sawitzky ◽  
Barbara J. M. Stoehr ◽  
Peggy Stock ◽  
Dominik Menhofer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Janus Kinase ◽  
Gh Secretion ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
I Gene ◽  
Gh Resistance

GH is a well established regulator of growth, lipid, and glucose metabolism and therefore important for fuel utilization. However, little is known about the effects of macronutrients on the GH/IGF system. We used low-carbohydrate/high-fat diets (LC-HFD) as a model to study the impact of fat, protein, and carbohydrates on the GH/IGF-axis; 12-wk-old Wistar rats were fed either regular chow, a moderate, protein-matched LC-HFD, or a ketogenic LC-HFD (percentage of fat/protein/carbohydrates: chow, 16.7/19/64.3; LC-HF-1, 78.7/19.1/2.2; LC-HF-2, 92.8/5.5/1.7). After 4 wk, body and tibia length, lean body mass, and fat pad weights were measured. Furthermore, we investigated the effects of LC-HFD on 1) secretion of GH and GH-dependent factors, 2) expression and signaling of components of the GH/IGF system in liver and muscle, and 3) hypothalamic and pituitary regulation of GH release. Serum concentrations of IGF-I, IGF binding protein-1, and IGF binding protein-3 were lower with LC-HF-1 and LC-HF-2 (P &lt; 0.01). Both LC-HFD-reduced hepatic GH receptor mRNA and protein expression, decreased basal levels of total and phosphorylated Janus kinase/signal transducers and activators of transcription signaling proteins and reduced hepatic IGF-I gene expression. Hypothalamic somatostatin expression was reduced only with LC-HF-1, leading to increased pituitary GH secretion, higher IGF-I gene expression, and activation of IGF-dependent signaling pathways in skeletal muscle. In contrast, despite severely reduced IGF-I concentrations, GH secretion did not increase with LC-HF-2 diet. In conclusion, lack of carbohydrates in LC-HFD induces hepatic GH resistance. Furthermore, central feedback mechanisms of the GH/IGF system are impaired with extreme, ketogenic LC-HFD.

scholarly journals Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression

2006 ◽  
Vol 188 (3) ◽  
pp. 503-511 ◽  
Author(s):  
M Granado ◽  
A I Martín ◽  
T Priego ◽  
M A Villanúa ◽  
A López-Calderón
Keyword(s):  
Gene Expression ◽  
Kupffer Cells ◽  
Inhibitory Effect ◽  
Gadolinium Chloride ◽  
Serum Concentrations ◽  
Tnf Α ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the IGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P < 0.01), as well as in their gene expression in the liver. LPS-injected rats had increased serum concentrations of ACTH, corticosterone (P < 0.05), tumour necrosis factor-α (TNF-α) and nitrites (P < 0.01). Pretreatment of the animals with gadolinium chloride blocked the inhibitory effect of LPS on body weight, and on serum concentrations of IGF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serum concentrations of ACTH, corticosterone and TNF-α. These results suggest that Kupffer cells are important mediators in the inhibitory effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serum concentrations of IGF-I and IGFBP-3.

scholarly journals The ovarian expression of mRNAs for aromatase, IGF-I receptor, IGF-binding protein-2, -4 and -5, leptin and leptin receptor in cycling ewes after three days of leptin infusion

Reproduction ◽  
2005 ◽  
Vol 130 (6) ◽  
pp. 869-881 ◽  
Author(s):  
M Muñoz-Gutiérrez ◽  
P A Findlay ◽  
C L Adam ◽  
G Wax ◽  
B K Campbell ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Leptin Receptor ◽  
Binding Protein ◽  
Control Group ◽  
Igf System ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Oestradiol Production

An experiment was carried out to determine the pattern of follicular expression of mRNAs for aromatase, IGF-I receptor (IGF-IR), IGF-binding protein (IGFBP)-2, -4 and -5, leptin and the long form of the leptin receptor (Ob-Rb) in ten ewes infused with human recombinant leptin (n= 5; 1 μg/h) or saline (n= 5) for 72 h in the luteal phase of the oestrous cycle. At the end of infusion a follicular phase was induced with a luteolytic dose of a prostaglandin F2α analogue and the ovaries were collected 32 h later. One ovary from each ewe was serially sectioned at 10 μm using a cryostat at −20 °C. All follicles >1 mm in diameter were counted and probed with specific oligoprobes for aromatase, IGF-IR and IGFBP-2, -4 and -5 and specific riboprobes for leptin and Ob-Rb. Leptin mRNA was detected in theca and granulosa cells and Ob-Rb mRNA was detected only in granulosa cells, of some, but not all antral follicles. Leptin doubled the number of follicles with a diameter ≥3.5 mm (1.0 ± 0.36 (s.e.m.) vs 2.4 ± 0.24; control vs leptin;P< 0.02) but had no effect on the number of ≥1 < 3.5 mm follicles. Leptin had no effect on the number of follicles expressing aromatase mRNA but it decreased significantly the number of follicles expressing mRNA for IGF-IR (10.7 ± 0.79 vs 7.4 ± 0.81; control vs leptin;P< 0.05), IGFBP-2 (10.0 ± 0.82 vs 5.2 ± 0.87; control vs leptin;P< 0.05) and IGFBP-5 (5.2 ± 1.60 vs 1.2 ± 0.30; control vs leptin;P< 0.05). Leptin increased the diameter of IGFBP-2 mRNA-positive follicles (1.5 ± 0.15 vs 2.2 ± 0.31 mm; control vs leptin;P< 0.05) and increased follicular mRNA expression for IGFBP-2 (0.30 ± 0.021 vs 0.39 ± 0.027 arbitrary units; control vs leptin;P< 0.05) and IGFBP-5 (0.46 ± 0.019 vs 0.25 ± 0.053 arbitary units; control vs leptin;P< 0.05). The mRNA for IGFBP-4 was detected in the theca of only two follicles from the control group. Leptin increased the number of follicles expressing Ob-Rb mRNA (0.25 ± 0.25 vs 1.40 ± 1.17; control vs leptin;P< 0.05) but had no effect on the number expressing leptin mRNA. Leptin decreased plasma concentrations of oestradiol (P< 0.05) and increased concentrations of FSH (P< 0.001) and insulin (P< 0.001), with no effect on glucose concentrations. These data show that: (i) ovine granulosa cells express mRNA for Ob-Rb and leptin and (ii) leptin increased the number of follicles ≥3.5 mm. Furthermore, the data suggest that suppression of oestradiol production by leptin is not mediated by inhibition of aromatase gene expression. Finally, the data indicate that the action of leptin in ovarian follicles is mediated by the IGF system, because leptin increased mRNA expression of IGFBP-2 and -5. Leptin also decreased the number of follicles expressing IGF-IR and IGFBP-2 and -5. We suggest that these actions of leptin on the IGF system decrease the bioavailability of IGF-I, resulting in decreased oestradiol production.

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