scholarly journals The GH/IGF-I axis in the brushtail possum (Trichosurus vulpecula) pouch young

2003 ◽  
Vol 176 (2) ◽  
pp. 219-225 ◽  
Author(s):  
MC Saunders ◽  
RT Gemmell ◽  
JD Curlewis
Keyword(s):  
Mrna Expression ◽  
Fetal Liver ◽  
Post Partum ◽  
Fold Increase ◽  
High Plasma ◽  
Brushtail Possum ◽  
Trichosurus Vulpecula ◽  
Igf I ◽  
Plasma Gh ◽  
Igfbp 3

Plasma and pituitary GH concentrations and liver GH receptor (GHR), IGF-I and IGF-binding protein-3 (IGFBP-3) mRNA expression were determined in brushtail possum (Trichosurus vulpecula) pouch young aged 12-150 days post-partum and in adults. Mean plasma GH concentrations were highest, measuring around 150 ng/ml, from 12 to 100 days post-partum, and thereafter declined so that by 150 days post-partum levels were not significantly different from those in adults (10.8+/-1.8 ng/ml (S.E.M.)). In contrast to plasma levels, pituitary GH content increased markedly throughout pouch life, with an 87-fold increase between 12 and 150 days post-partum. However, when expressed per gram body weight, pituitary content was relatively constant between 25 and 150 days post-partum, indicating that the decline in plasma GH after 100 days post-partum was not due to decreased synthesis and/or storage of GH in the pituitary gland. Expression of GHR, IGF-I and IGFBP-3 mRNAs was determined by semi-quantitative RT-PCR. Liver GHR and IGF-I mRNA expression were low at 12 and 25 days post-partum and did not show sustained and significant increases (P<0.05) until 125 and 150 days post-partum. IGFBP-3 expression was also low at 12 days post-partum but then increased rapidly to a maximum at 50 days post-partum and thereafter declined. For all three mRNAs, liver expression at day 150 was not significantly different from that in adults. These patterns of gene expression for GHR and IGF-I suggest that the possum liver is resistant to the high plasma GH concentrations during early pouch life and in this way is similar to the fetal liver of some eutherian mammals.

scholarly journals Plasma growth hormone and growth hormone-binding protein during development in the marsupial brushtail possum (Trichosurus vulpecula)

2002 ◽  
Vol 173 (3) ◽  
pp. 507-515 ◽  
Author(s):  
MC Saunders ◽  
RT Gemmell ◽  
MJ Waters ◽  
JD Curlewis
Keyword(s):  
Growth Hormone ◽  
Binding Protein ◽  
Post Partum ◽  
Brushtail Possum ◽  
Trichosurus Vulpecula ◽  
Hormone Binding ◽  
Adult Individual ◽  
Gh Receptor ◽  
Growth Hormone Binding Protein ◽  
Hormone Binding Protein

Plasma concentrations of growth hormone (GH) were measured in the brushtail possum (Trichosurus vulpecula) pouch young from 25 through to 198 days post-partum (n=71). GH concentrations were highest early in pouch life (around 100 ng/ml), and thereafter declined in an exponential fashion to reach adult concentrations (10.8+/-1.8 ng/ml; n=21) by approximately 121-145 days post-partum, one to two months before the young is weaned. Growth hormone-binding protein (GHBP), which has been shown to modify the cellular actions of GH in eutherian mammals, was identified for the first time in a marsupial. Based on size exclusion gel filtration, possum GHBP had an estimated molecular mass of approximately 65 kDa, similar to that identified in other mammalian species, and binding of (125)I-labelled human GH (hGH) was displaced by excess hGH (20 microg). An immunoprecipitation method, in which plasma GHBP was rendered polyethylene glycol precipitable with a monoclonal antibody to the rabbit GHBP/GH receptor (MAb 43) and labelled with (125)I-hGH, was used to quantitate plasma GHBP by Scatchard analysis in the developing (pooled plasma samples) and adult (individual animals) possums. Binding affinity (K(a)) values in pouch young aged between 45 and 54 and 144 and 153 days post-partum varied between 1.0 and 2.4 x 10(9)/M, which was slightly higher than that in adult plasma (0.96+/-0.2 x 10(9)/M, n=6). Binding capacity (B(max)) values increased from non-detectable levels in animals aged 25-38 days post-partum to reach concentrations around half that seen in the adult (1.4+/-0.2 x 10(-9) M) by about 117 days post-partum and remained at this level until 153 days post-partum. Therefore, in early pouch life when plasma GH concentrations are highest, the very low concentrations of GHBP are unlikely to be important in terms of competing with GH-receptor for ligand or altering the half-life of circulating GH.

IGFBP mRNA expression in small intestine of rat during postnatal development

2001 ◽  
Vol 281 (6) ◽  
pp. G1378-G1384 ◽  
Author(s):  
C. A. Shoubridge ◽  
C.-B. Steeb ◽  
L. C. Read
Keyword(s):  
Mrna Expression ◽  
Postnatal Development ◽  
Age Groups ◽  
Rat Intestine ◽  
Age Related ◽  
Igf I ◽  
Igf Binding ◽  
Old Rats ◽  
Igf Binding Protein ◽  
Igfbp 3

In contrast to the adult gut, the immature intestine is refractory to subcutaneously infused insulin-like growth factor I (IGF-I). IGF binding protein (IGFBP) mRNA expression was characterized in intestinal tissues from 6-, 19-, and 90-day-old rats to determine if changes in local expression could account for this age-related change in IGF-I potency. For all age groups, IGFBP-3 to -6, but not IGFBP-1 or -2, were detected by Northern blot analysis. IGFBP-3, -4, and -5 were more intensely expressed in the 6-day-old rat intestine compared with weanling or adult tissue. In contrast, IGFBP-6 expression peaked at the time of weaning. In situ hybridization showed IGFBP-3 to -6 expression was confined to cells of the lamina propria and submucosa and also in the muscularis layer for IGFBP-5. Furthermore, the pattern of IGFBP-5 localization in the intestine changed with development. The findings indicate that the expression of IGFBP-3 to -6 is higher in the immature intestine compared with the adult intestine, suggesting locally produced IGFBPs may inhibit systemically derived IGF-I action in the intestine. Therefore, changes to local IGFBP expression may contribute to the varying response of the rat intestine to IGF-I peptides during postnatal development.

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 ◽  
2000 ◽  
pp. 407-416 ◽  
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.

DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells

2006 ◽  
Vol 290 (5) ◽  
pp. E952-E960 ◽  
Author(s):  
Hanh Le ◽  
Julia T. Arnold ◽  
Kimberly K. McFann ◽  
Marc R. Blackman
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Mrna Expression ◽  
Protein Secretion ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Time Dependent ◽  
Dependent Manner ◽  
Igf I ◽  
Igfbp 3

Prostate cancer is one of the four most common cancers in the United States, affecting one of six men. Increased serum levels of androgens and IGF-I are associated with an augmented risk of prostate cancer. Dihydrotestosterone (DHT) and testosterone (T) stimulate prostate cancer cell growth, development, and function, whereas the effects of DHT and T in prostate stromal cells, and of dehydroepiandrosterone (DHEA) in prostate cancer or stromal cells, are uncertain. We investigated the actions of DHT, T, DHEA, and estradiol (E2) on insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor (R), IGF-binding protein (IGFBP)-2, IGFBP-3, and IGFBP-5 in primary cultures of human prostatic stromal cells by assessing cell proliferation, mRNA expression, and protein secretion by MTT growth assay, quantitative real-time PCR, and ELISA, respectively. DHT and T each increased IGF-I (7-fold) and decreased IGFBP-3 (2-fold) mRNA expression and protein secretion in a dose- and time-dependent manner and increased IGFBP-2 (2-fold) mRNA in a dose- and time-dependent manner. DHEA and E2did not significantly alter these measures. Flutamide abolished the DHT-modulated increases in IGF-I and IGFBP-2, suggesting that the influences of DHT and T on these measures were androgen receptor mediated. None of the four steroids significantly affected IGF-IR, IGF-II, or IGFBP-5 mRNA levels or stromal cell proliferation. The effects of DHT on IGF-I, IGFBP-2, and IGFBP-3 were more pronounced in stromal cultures that did not express desmin. These data suggest that DHT and T promote prostate growth partly via modulation of the stromal cell IGF axis, with potential paracrine effects on prostate epithelial cells.

Resection-induced colonic adaptation is augmented by IGF-I and associated with upregulation of colonic IGF-I mRNA

1995 ◽  
Vol 269 (6) ◽  
pp. G974-G980 ◽  
Author(s):  
M. P. Mantell ◽  
T. R. Ziegler ◽  
W. T. Adamson ◽  
J. A. Roth ◽  
W. Zhang ◽  
...  
Keyword(s):  
Small Bowel ◽  
Water Absorption ◽  
Mrna Expression ◽  
Day Treatment ◽  
Intestinal Resection ◽  
Sprague Dawley ◽  
Igf I ◽  
Mucosal Growth ◽  
Igfbp 3

The effects of exogenous insulin-like growth factor-I (IGF-I) on colonic adaptation were examined in male Sprague-Dawley rats (n = 60, 225-275 mg) after either a 60% small bowel and cecal resection (RX) or mid-small bowel transection with reanastomosis (TX). Animals received a 7-day treatment with either IGF-I (2.4 mg.kg-1.day-1) or vehicle (V; 0.1 mol/l acetic acid). Body weight decreased significantly after resection (-25.6 +/- 4.0 g; P < 0.05 vs. TX/V). IGF-I treatment significantly reduced weight loss after resection (-12.4 +/- 3.8 g; P < 0.01 vs. RX/V) and induced significant weight gain after transection (15.6 +/- 4.0 g; P < 0.05 vs. TX/V). Plasma IGF-I decreased with resection (526 +/- 41 TX/V vs. 344 +/- 17 ng/ml RX/V; P < 0.01). IGF-I treatment significantly increased plasma IGF-I levels (805 +/- 100 ng/ml TX/IGF, 677 +/- 56 ng/ml RX/IGF). After resection, IGF-I treatment significantly increased colonic mucosal weight, DNA, protein content, and crypt depth when compared with resection alone (P < 0.05). Colonic water absorption, measured by an in vivo [3H]polyethylene glycol assay, was significantly increased by IGF-I treatment in resected animals (399 +/- 23 RX/IGF vs. 306 +/- 32 microliter.cm-1.h-1 RX/V; P < 0.05). Resection resulted in increased steady-state colonic IGF-I mRNA (182% of TX/V; P < 0.01) without significantly affecting IGF-I receptor mRNA expression. Regulation of IGF binding protein (BP)-3 and -4 was discoordinate, with IGFBP-3 mRNA tending to decrease with resection (67% of TX/V; P is not significant) and IGFBP-4 increasing significantly (191% of TX/V; P < 0.05). An important role for IGF-I in colonic adaptation after massive intestinal resection is indicated by 1) significantly enhanced colonic mucosal growth and water absorption with IGF-I treatment and 2) postresection upregulation of colonic IGF-I mRNA and alteration of IGFBP-3 and IGFBP-4 mRNA expression.

scholarly journals Sexual Dimorphism in the Growth Hormone and Insulin-Like Growth Factor Axis at Birth

2003 ◽  
Vol 88 (8) ◽  
pp. 3708-3714 ◽  
Author(s):  
Michael P. P. Geary ◽  
P. Jane Pringle ◽  
Charles H. Rodeck ◽  
John C. P. Kingdom ◽  
Peter C. Hindmarsh
Keyword(s):  
Birth Weight ◽  
Head Circumference ◽  
Mode Of Delivery ◽  
Plasma Concentrations ◽  
Birth Size ◽  
Maternal Height ◽  
Cord Plasma ◽  
Igf I ◽  
Plasma Gh ◽  
Igfbp 3

In rodents and humans there is a sexually dimorphic pattern of GH secretion that influences the serum concentration of IGF-I. Pattern differences can be identified in children, but it is not known how early this difference is established. We studied the plasma concentrations of IGF-I, IGF-II, IGF-binding protein-3 (BP-3), and GH in cord blood taken from the offspring of 1650 singleton Caucasian pregnancies born at term and related these values to birth weight, length, and head circumference. Pregnancies complicated by preterm delivery, antepartum hemorrhage, pregnancy-induced hypertension, preeclampsia, or gestational diabetes and where cigarette smoking continued were excluded, resulting in a cohort of 987. Cord plasma concentrations of IGF-I, IGF-II, and IGFBP-3 were influenced by factors influencing birth size: gestational age at delivery, mode of delivery, maternal height, and parity of the mother. Plasma GH concentrations were inversely related to the plasma concentrations of IGF-I and IGFBP-3; 10.2% of the variability in cord plasma IGF-I concentration and 2.7% for IGFBP-3 was explained by sex of the offspring and parity. None of the factors, apart from maternal height, influenced cord serum IGF-II concentrations (adjusted r2 = 1%). Sex of the baby, mode of delivery, and parity influenced cord serum GH concentrations (adjusted r2 = 2.6%). Birth weight, length, and head circumference measurements were greater in males than females (P &lt; 0.001). Mean cord plasma concentrations of IGF-I (males, 66.4 ± 1.2 μg/liter; females, 74.5 ± 1.3 μg/liter; P &lt; 0.001) and IGFBP-3 (males, 910 ± 13 μg/liter; females 978 ± 13 μg/liter; P &lt; 0.001) were significantly lower in males than females. Cord plasma GH concentrations were higher in males than females (males, 30.0 ± 1.2 mU/liter; females, 26.9 ± 1.1 mU/liter; P = 0.05), but no difference was noted between the sexes for IGF-II (males, 508 ± 6 μg/liter; females, 519 ± 6 μg/liter; P = NS). After adjustment for gestational age, parity, and maternal height, cord plasma concentrations of IGF-I and IGFBP-3 along with sex explained 38.0% of the variability in birth weight, 25.0% in birth length, and 22.7% in head circumference. These data demonstrate that in a group of singleton Caucasian babies born at term, cord plasma IGF-I, IGFBP-3, and GH concentrations relate to birth size, with evidence for sexual dimorphism in the GH-IGF axis.

scholarly journals Effect of negative energy balance on the insulin-like growth factor system in pre-recruitment ovarian follicles of post partum dairy cows

Reproduction ◽  
2007 ◽  
Vol 133 (3) ◽  
pp. 627-639 ◽  
Author(s):  
S Llewellyn ◽  
R Fitzpatrick ◽  
D A Kenny ◽  
J J Murphy ◽  
R J Scaramuzzi ◽  
...  
Keyword(s):  
Energy Balance ◽  
Mrna Expression ◽  
Post Partum ◽  
Ovarian Follicles ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Igf Binding Proteins ◽  
Igf I ◽  
Igf Binding ◽  
Ovarian Cyclicity

Post partumnegative energy balance (NEB) in dairy cattle is associated with a delayed return to ovarian cyclicity and reduced fertility. This study compared the IGF system of pre-recruitment ovarian follicles between cows in mild (n= 6) or severe (n= 6) NEB during early lactation. Ovaries were collected in the second weekpost partum, when circulating concentrations of IGF-I and glucose were lower (P< 0.01) in severe NEB cows. mRNA expression for IGF-II, type 1 IGF receptor (IGF-1R) and IGF-binding proteins (IGFBP)-1 to IGFBP-6 was determined byin situhybridisation in individual follicles using radiolabelled oligonucleotide probes. Follicles were classified as very small (1–2.5 mm) or small (2.5–5 mm) and healthy or atretic. Relative mRNA concentrations were measured as optical density (OD) units using image analysis. Thecal IGF-II mRNA expression was highest in very small, healthy follicles (P< 0.05). Granulosa cell IGFBP-2 was the only component to change with EB status, with higher mRNA expression in mild compared with severe NEB cows (P< 0.05). IGFBP-1 and IGFBP-3 mRNA expression were undetectable. IGF-1R, IGFBP-4 and IGFBP-5 mRNA expression were not significantly altered by follicle size or health, but IGFBP-5 tended to increase in atretic follicles. The pattern of IGFBP-6 mRNA expression in theca paralleled that of IGF-II mRNA, with higher (P< 0.05) levels in healthy, very small follicles. In conclusion, the reduced expression of IGFBP-2 mRNA in severe NEB cows may alter the bioavailability of circulating IGF-I and locally produced IGF-II to modulate the pre-recruitment stages of follicles required to maintain normalpost partumovarian cyclicity.

Growth-Rates of the Bandicoot Isoodon-Macrourus and the Brushtail Possum Trichosurus-Vulpecula

1993 ◽  
Vol 41 (2) ◽  
pp. 141 ◽  
Author(s):  
RT Gemmell ◽  
JK Hendrikz
Keyword(s):  
Growth Rate ◽  
Body Weight ◽  
Growth Curve ◽  
Growth Rates ◽  
Post Partum ◽  
Quadratic Equation ◽  
The Body ◽  
Brushtail Possum ◽  
Trichosurus Vulpecula ◽  
Iterative Analysis

Although the bandicoot Isoodon macrourus and the brushtail possum Trichosurus vulpecula give birth to similar-size young, about 200 mg, the pouch young of the bandicoot grow more quickly than those of the possum. The bandicoot is weaned at 59 days when the body weight is between 90 and 250 g. A young possum weighs about 20 g at Day 60 and between 780 and 1031 g when weaned at Day 170-180 post partum. The body weight of both species has been described previously as a continuous curve expressed by a quadratic equation. In this study, instead of assuming the growth curve to be continuous, the growth curve has been expressed as two components. The growth rates of both species were similar from birth until Day 12 post partum; the bandicoot then had a faster growth rate. The results from iterative analysis indicated a change in growth rate at Day 30 (data for Days 31 and 32 were missing) and Day 96 post partum for the bandicoot and possum, respectively. Thus, both marsupials showed a change in growth rate as hair appeared, eyes opened and the young first left the pouch.

Effects of undernutrition and diabetes on serum and liver mRNA expression of IGFs and their binding proteins during rat development

1995 ◽  
Vol 145 (3) ◽  
pp. 427-440 ◽  
Author(s):  
F Rivero ◽  
L Goya ◽  
C Aláez ◽  
A M Pascual-Leone
Keyword(s):  
Body Weight ◽  
Mrna Expression ◽  
Binding Proteins ◽  
Fetal Liver ◽  
Decisive Role ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Igf I ◽  
Diabetic Population ◽  
Serum Gh

Abstract The purpose of the present study was to investigate the influence of nutrients and insulin on IGFs and their binding proteins (IGFBPs) during the fetal and neonatal periods of three rat populations: (a) rats undernourished by a 35% reduction in the diet from day 16 of gestation, (b) streptozotocin-induced diabetic rats from the same day, or 4 days after birth, and (c) control rats. Fetuses from the diabetic population showed a decrease in insulinemia at 19 and 21 days, along with an increase in glycemia at all stages. Neither glycemia nor insulinemia changed in the fetuses of undernourished mothers, but body weight was decreased at birth. Serum IGF-II decreased at 18 and 19 days of gestation in fetuses from undernourished mothers, and increased at 18, 19 and 21 days in fetuses from diabetic mothers. Serum IGFBPs of low molecular weight (IGFBP-1 and IGFBP-2) increased in the three fetal populations studied, although no changes in serum IGFBPs were found from the effect of undernutrition or diabetes, but fetal liver IGFBP-1 mRNA expression was found to be decreased in undernourished and diabetic animals as compared with controls. In neonatal rats, body weight, insulinemia and serum GH decreased in both undernourished and diabetic rats vs controls, while glycemia decreased in the undernourished and increased in the diabetic group. Serum IGF-II decreased only in diabetic rats and serum IGF-I decreased in both groups. The neonatal serum 30 kDa complex (IGFBP-1 and -2) also increased in undernutrition and diabetes parallel to the expression of mRNA. But, taken together, the changes in IGFBP peptide levels and liver mRNA expression strongly suggest that the 30 kDa complex seems to be composed mostly of IGFBP-1 in the diabetic group and of both IGFBP-1 and -2 in the undernourished animals. The studies of liver mRNA expression of IGFs and IGFBPs confirm the different metabolic control mechanism for the availability of IGFs by the IGFBPs, depending on the animal's maturity. The different adaptation shown by the diabetic neonatal population was confirmed by correlation studies between body weight, glycemia, insulinemia, IGF-I and IGFBPs. The different mechanism of adaptation in diabetic vs undernourished rats seems to be probably due to the decisive role played by hyperglycemia in the diabetic population, and also shows the crucial influence of nutritional status on IGFs and IGFBPs. Journal of Endocrinology (1995) 145, 427–440

scholarly journals Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery

1998 ◽  
pp. 164-169 ◽  
Author(s):  
G van den Berg ◽  
SM Pincus ◽  
M Frolich ◽  
JD Veldhuis ◽  
F Roelfsema
Keyword(s):  
Approximate Entropy ◽  
Pituitary Surgery ◽  
Early Recurrence ◽  
Gh Secretion ◽  
Control Subjects ◽  
Pituitary Dysfunction ◽  
Igf I ◽  
Active Acromegaly ◽  
Plasma Gh ◽  
Igfbp 3

The episodicity of 24 h GH release was studied in 18 patients with active acromegaly, 12 patients 7-10 days after pituitary surgery, 14 patients long after operation (3-17 years), and 21 healthy gender- and age-matched control subjects, using a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). Blood samples were taken at 10-min intervals for 24 h, and plasma GH concentrations were measured by immunofluorometric assay (detection limit 11.5 ng/l). For this study we selected operated patients who were biochemically in remission, defined by normal circulating IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations, normal glucose-suppressed plasma GH concentration (<0.38 microg/l), and the normalization of the paradoxical rise of GH to TRH or GnRH. In patients with active acromegaly ApEn was 1.23+/-0.04, with no overlap with the control subjects (P = 1.2 x 10[-16]), who had an ApEn of 0.40+/-0.04. ApEn in patients shortly after surgery was 0.71+/-0.09 (P < 0.001 vs controls), and long after surgery 0.56+/-0.05 (P < 0.011 vs controls). ApEn values in treated and untreated patients correlated significantly with the plasma concentration of IGF-I (r=0.531) and IGFBP-3 (r=0.598), and the log-transformed 24h GH secretion rate (r=0.749). Shortly after surgery only one-third of the patients had a normal ApEn value, whereas long after surgery about 70% of the patients had a normal ApEn value. Although ApEn eventually normalized in about 70% of the operated patients, the cause of the persistence of abnormal GH release in the remainder of the subjects is not known, and might reflect permanent hypothalamic-pituitary dysfunction or a very early recurrence of the somatotroph adenoma.

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