IGF-I, IGF-II, 'free' IGF-I and IGF-binding proteins-2 to -6 during high-dose oestrogen treatment in constitutionally tall girls

Abstract

Objective: To investigate the effect of high-dose oestrogen treatment on IGF-I, IGF-II, free-dissociable IGF-I and the IGF-binding proteins (IGFBP)-2 to -6 in girls with constitutional tall stature. Methods: In patient cohort 1, blood samples were drawn before and after 3 months of daily oral treatment with 0.1 mg ethinyloestradiol. In cohort 2, samples were collected at the end of the treatment period and 3 to 6 months afterwards. IGFs and IGFBPs were analysed by specific immunoassays and by Western ligand blot. Results: Total IGF-I decreased significantly on oestrogen treatment and increased again after oestrogen withdrawal. Ligand blot analysis showed a clear reduction in a 34 kDa band, corresponding to IGFBP-2, and a strong induction of a 24 kDa band, corresponding to the non-glycosylated form of IGFBP-4. These changes were confirmed by specific immunological methods. The serum levels of IGFBP-3, IGFBP-5 and IGFBP-6 remained unchanged during the first 3 months of treatment. In cohort 2, IGFBP-3 and IGFBP-6 increased after oestrogen withdrawal. Free-dissociable IGF-I fell to 35^4% during oestrogen therapy and rose again when the treatment was stopped. Conclusions: Oestrogens modulate the serum concentrations of several components of the IGF system. The fall in total IGF-I is not explained by a decrease in IGFBPs but probably results from a decreased synthesis.

IGFBP-6 five years on; not so ‘forgotten’?

“…Circulating IGFBP-6 levels are lower in adult females than males, but oestrogen treatment had no effect on IGFBP-6 levels in constitutionally tall girls [59]. Within the monkey ovary, IGFBPs are expressed in distinctive distributions, with IGFBP-6 mRNA levels being highest in the surface epithelium, similar to that seen in humans [60].…”

Differential expression of breast cancer-associated genes between stage- and age-matched tumor specimens from African- and Caucasian-American Women diagnosed with breast cancer

“…The expression of AR [57,58], BCL2 [57-59], CCND1 [57,58,60], GATA3 [57,58,61,62], IL6ST [57,58], MUC1 [58,63,64], PGR [57,65], SERPINE1 [66,67], HSPB1 [58,68,69] and STC2 [57,58,69,70] have been positively associated with ESR1 expression and/or upregulated by ESR1 . Other studies have found estrogen can directly upregulate transcription of AR [57], GATA3 [57], IGFBP2 [71,72], KRT19 [73], and MUC1 [64], PGR [57,74,75], SERPINE1 [76], HSPB1 [77-79], SERPINA3 [80,81], SERPINE1 [76], and STC2 [57,69,70]. In support of these studies, we also found that the expression of AR, BCL2, GATA3, IL6ST, MUC1, PGR, SERPINE1 , and HSPB1 , were significantly associated with ESR1 expression in AAW; although, only KRT19 and CCND1 were positively correlated with ESR1 levels in American women of Caucasian descent.…”

Free dissociable insulin‐like growth factor I (IGF‐I), total IGF‐I and their binding proteins in girls with Turner syndrome during long‐term growth hormone treatment

“…One of the few studies to have evaluated the effect of oestrogens on free IGF-I found that high-dose oestrogen treatment in constitutionally tall girls leads to a considerable decrease in free IGF-I. 25 On the other hand, an ultrafiltration-based assay established that despite an increase in IGFBP-3 proteolysis, adult TS patients undergoing oestrogen therapy did not show significant changes in circulating free IGF-I levels. 20 However, our own assessment of the influence of oestrogen therapy was made in a model along with other variables.…”