scholarly journals Impact of gender and androgen status on IGF-I levels in normal and GH-deficient adults

1999 ◽  
pp. 601-608 ◽  
Author(s):  
S Fisker ◽  
JO Jorgensen ◽  
N Vahl ◽  
H Orskov ◽  
JS Christiansen

OBJECTIVE: The regulation of IGF-I levels is complex and not only dependent on GH status, as the diagnostic sensitivity of serum IGF-I levels for GH deficiency (GHD) in adults is low. Other GH-related parameters have so far not proven to be of additional diagnostic value in GHD adults. In the present study we evaluated the impact of gender and androgen status on IGF-I levels and the diagnostic value of IGF-I and GH-related parameters in a population of adult hypopituitary patients and age- and gender-matched healthy subjects. DESIGN: A cross-sectional study. SUBJECTS: Fifty-nine GHD patients (40 males, mean age 39.3+/-1.7 (s.e.m.) years, and 19 females, mean age 41.9+/-2.6 years) and 69 healthy subjects (42 males, mean age 36. 7+/-1.5 years, and 27 females, mean age 38.9+/-2.1 years). RESULTS: IGF-I levels were low in the GHD patients (91+/-7 vs 173+/-7 microgram/l, P<0.001), and lower in female patients than in male (68+/-10 vs 100+/-8 microgram/l, P=0.03). In the control group there was no gender-related difference in IGF-I levels (males: 178+/-8, females: 164+/-12 microgram/l, P=0.23). IGF-II and IGF-binding protein-3 (IGFBP-3) were also decreased in GHD without any gender-related differences. GH-binding protein (GHBP) levels were increased in the patient group. The diagnostic sensitivity (%) of IGF-I, IGF-I/GHBP, IGF-I/IGFBP-3, and of the combination of IGF-I plus IGF-II (both low or one normal and one low), was higher in female patients than in male (IGF-I: 57.8 vs 22.0, P<0.0001; IGF-I/GHBP: 84.2 vs 48.8, P=0. 002; IGF-I/IGFBP-3: 36.8 vs 7.3 P=0.001; IGF-I+IGF-II: 77.8 vs 52.6, P=0.01). Testosterone levels were reduced in the female patients compared with female controls (0.5+/-0.3 vs 2.1+/-0.2nmol/l, P<0.001). Forward regression analyses revealed that IGFBP-3 was a significant predictor of IGF-I levels in both patients and healthy subjects. In a combined analysis of both patients and controls, sex hormone-binding globulin (SHBG) level was the main contributor as an explanatory variable. Gender and prolactin also predicted IGF-I in patients, whereas SHBG and estradiol were significant predictors only in the control group. CONCLUSION: (i) Levels of IGF-I, and of IGF-I/IGFBP-3 and IGF-I/GHBP ratios are lower in females compared with male adult GHD patients. (ii) IGF-I/GHBP has a high diagnostic sensitivity of adult GHD, in particular in women. (iii) We hypothesize that the gender difference in IGF-I levels among adult GHD patients are causally related to the very low androgen levels observed among females.

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2164-2173 ◽  
Author(s):  
Woo-Young Kim ◽  
Mi-Jung Kim ◽  
Hojin Moon ◽  
Ping Yuan ◽  
Jin-Soo Kim ◽  
...  

The IGF axis has been implicated in the risk of various cancers. We previously reported a potential role of tissue-derived IGF in lung tumor formation and progression. However, the role of IGF-binding protein (IGFBP)-3, a major IGFBP, on the activity of tissue-driven IGF in lung cancer development is largely unknown. Here, we show that IGF-I, but not IGF-II, protein levels in non-small-cell lung cancer (NSCLC) were significantly higher than those in normal and hyperplastic bronchial epithelium. We found that IGF-I and IGFBP-3 levels in NSCLC tissue specimens were significantly correlated with phosphorylated IGF-IR (pIGF-IR) expression. We investigated the impact of IGFBP-3 expression on the activity of tissue-driven IGF-I in lung cancer development using mice carrying lung-specific human IGF-I transgene (Tg), a germline-null mutation of IGFBP-3, or both. Compared with wild-type (BP3+/+) mice, mice carrying heterozygous (BP3+/−) or homozygous (BP3−/−) deletion of IGFBP-3 alleles exhibited decreases in circulating IGFBP-3 and IGF-I. Unexpectedly, IGFTg mice with 50% of physiological IGFBP-3 (BP3+/−; IGFTg) showed higher levels of pIGF-IR/IR and a greater degree of spontaneous or tobacco carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung tumor development and progression than did the IGFTg mice with normal (BP3+/+;IGFTg) or homozygous deletion of IGFBP-3 (BP3−/−; IGFTg). These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.


1993 ◽  
Vol 128 (5) ◽  
pp. 397-404 ◽  

In the present study of twenty-two patients with Cushing's syndrome, serum insulin-like growth factor (IGF)-I concentrations were normal to high with an increased mean IGF-I concentration, 40% above that of healthy subjects of the same age (p<0.001). Serum IGF-II concentrations were normal. The morning serum IGF binding protein (IGFBP)-l concentrations were within the range of healthy controls. IGFBP-1 was inversely correlated to the IGF-I concentration (p<0.001) and to the 24 h urinary cortisol excretion (p <0.005) with a combined R squared value of 0.58. In contrast to IGFBP-l, serum IGFBP-2 and IGFBP-3 concentrations were elevated by 1.89±1.78 sd and 0.92±0.78 sd (mean±2 sd), respectively. Although increased, the serum IGFBP-2 concentration was inversely correlated to the IGF-I concentration (r= −0.67, p<0.001). Immunoreactive IGFBP-3 was increased in proportion to IGF-I and the molar ratio [IGFBP-3]: [IGF-I]±[IGF-II] was close to unity (1.04±0.14), as that of healthy subjects. In serum from patients with Cushing's syndrome, with increased immunoreactive IGFBP-3, there was a corresponding increase in intact glycosylated 40–43 kDa IGFBP-3 as determined by Western ligand blotting. Neutral size chromatography of serum from patients with Cushing's syndrome showed that IGF-I and IGFBP-3 immunoreactivity were predominantly found at the elution volume of the ternary 1 50 kDa IGF-I/IGFBP-3/acid labile subunit complex and a similar pattern was displayed by normal serum. We conclude that the catabolism and impairment of growth in patients with Cushing's syndrome cannot be attributed to the suppression of the GH-endocrine IGF-I axis. Furthermore, our findings suggest that the previously reported increased IGF inhibitory activity, of low molecular weight, in Cushing's serum could not be attributed to IGFBP-3, IGFBP-3 fragments or IGFBP-1. The possible role of IGFBP-2 or other IGFBPs in blocking the effects of IGFs has to be further evaluated.


2002 ◽  
pp. 319-323 ◽  
Author(s):  
Y Rakover ◽  
A Silbergeld ◽  
I Lavi ◽  
R Masalha ◽  
IB Shlomo

OBJECTIVES: In the majority of children with short stature, the etiology is unknown. Mutations of the GH receptor (GHR) have been reported in a few children with apparent idiopathic short stature (ISS). These patients had low IGF-I, IGF-binding protein-3 (IGFBP-3) and GH-binding protein (GHBP), but a normal or exaggerated GH response to provocative stimuli, suggestive of partial GH insensitivity (GHI). We attempted to identify children with partial GHI syndrome, based on their response to GH provocative stimuli and other parameters of the GH-IGF-I axis. SUBJECTS AND METHODS: One hundred and sixty-four pre-pubertal children (97 boys, 67 girls) aged 7.2 (0.5-16.75) years were studied. All had short stature with height <3rd centile. The weight, bone age (BA) and body mass index (BMI) of the subjects, as well as the parents' heights and mid parental height (MPH) were assessed. Basal blood samples were taken for IGF-I, IGFBP-3 and GHBP. All subjects underwent a GH provocative test with either clonidine, arginine or insulin. The subjects were divided into three groups: (A) patients with peak GH concentration <18 mIU/l in two different provocative tests (GH deficiency - GHD, n=33); (B) patients with peak GH between 18.2 and 39.8 mIU/l (normal response, n=78); (C) patients with peak GH >40 mIU/l (exaggerated GH response, n=53). RESULTS: No significant differences were found in age, height (standard deviation score (SDS)), parental height (SDS) and the difference between chronological age and bone age (DeltaBA) between the groups. Patients with GHD were heavier (P=0.039) and had significantly higher BMI (SDS) (P=0.001) than the other groups. MPH (SDS) was lower in the group of exaggerated responders (P=0.04) compared with the other groups. No significant differences were found between the groups for the biochemical parameters when expressed nominally or in SDS, except for IGFBP-3 (SDS), which was lower in the GHD group (P=0.005). The GHBP levels were not lower in the group of exaggerated GH response to provocative stimuli. Height (SDS) correlated negatively with basal GH values in pooled data of all the subjects (r=-0.358, P<0.0001), in normal responders (r=-0.45, P<0.0001) and in the exaggerated responders (r=-0.341, P<0.0001), but not in the GHD group. CONCLUSION: Exaggerated GH response to provocative tests alone does not appear to be useful in identifying children with GHI.


2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  

2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  

Author(s):  
Nesma F. Radwan ◽  
Ahmed M. El Khyat ◽  
Adel E. El Gergawy ◽  
Hesham A. Salem

Background: The effect of endometriomas itself on the ovarian responsiveness that relate to ovarian reserve had been reported with several inconsistent results. In one study evaluated women with unilateral endometriomas, ovaries with disease showed lower response to ovarian stimulation than contralateral healthy ovaries .However, recent study on infertile women with un-operated unilateral small endometriomas did not support difference in ovarian responsiveness. The aim was to evaluate the impact of presence of endometriomas on ovarian reserve as measured by circulating AMH. Methods: This retrospective study was carried out on 80 female patients in childbearing period attending outpatient clinic and/or inpatient department of obstetrics and gynecology at Tanat University Hospital and the study was conducted directly after approval in the period from Apri, 2019 till April 2020. Group (A): Study group: 60 female patients aged between 20 to 30 years old GROUP (B): Control group: 20 age matched female with healthy ovaries. Results: there is no statistical significant difference between groups as regard Menarche (years), Regularity and Amount of menstrual blood flow. There is statistical significant difference between groups as regard fixed tender Right Ventricular Failure. But there are no statistical significant differences between groups as regard nodule in rectovaginal septum, fixed tender adnexal masses, association with adenomyosis and infertility. There is highly statistical significant difference between case and control groups as regard AMH levels. there are highly statistical significant positive correlation between duration of endometriosis and each of presence of pelvic pain, cyst diameter and Visual Analogue Scale. Conclusions:    Women with endometrioma have significantly lower serum AMH levels and seem to experience a more rapid decline in serum AMH levels than age matched counterparts, suggesting a harmful effect of endometrioma per se on ovarian reserve.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Mingxin Li ◽  
Lidong Zhai ◽  
Wanfu Wei

Rheumatoid arthritis, a synthesized form of adjuvant arthritis exhibited throughout many animal species, inhibits liver function and circulation of IGF-I and contributes to the degradation of skeletal muscle mass. One of the primary goals of the present study is determining whether a high-Methionine (high-Met) diet is capable of reducing the adverse effects of arthritis, namely, loss of body mass. Following adjuvant injection, forty arthritic rats were randomly assigned to either a control group with a basal diet or a high-Met group with the same basal diet + 0.5% Methionine. After 14 days all rats were terminated. The high-Met group exhibited an increase in body weight and food intake in comparison with the control group (P<0.05). High-Met diet debilitated arthritis-induced surges in the gastrocnemius in both atrogin-1 and the MuRF1 expressions; however, it was observed to have little to no effect on atrogin-1 and MuRF1 gene expression in soleus. At the same time, high-Met diet rats experienced a rise in IGF-I, with lowering of IGFBP-3 gene expression in the gastrocnemius and the soleus. These data suggest that arthritis severity can be partly attenuated by high-Met diet.


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