Effects of two oral contraceptives on plasma levels of insulin-like growth factor I (IGF-I) and growth hormone (hGH)

Balogh, A; Kauf, E; Vollanth, R; Gräser, G; Klinger, G; Oettel, M

doi:10.1016/s0010-7824(00)00176-1

Cited by 39 publications

(27 citation statements)

References 30 publications

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“…In the case of Runx2 and TGF-␤, this may help to enhance bone mass through effects on select phases of differentiated osteoblast function. In the case of C/EBP␦, this may account in large part for reciprocal, inverse changes in local and systemic expression of IGF-I that occur before and after menopause, and after hormone replacement therapy (37,38). The ER␣ agonist in osteoblast CM tends to reprise more fully the stimulatory effects of 17␤E on ERE, Runx2, and TGF-␤ activity, whereas it appears to be a less potent suppressor of C/EBP and AP-1 binding protein-dependent gene expression.…”

Section: Discussionmentioning

confidence: 99%

Expression of an estrogen receptor agonist in differentiating osteoblast cultures

McCarthy

Clough²,

Gundberg³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Osteoblasts respond in direct and indirect ways to estrogens, and age-dependent changes in hormone levels and bone health can be limited by focused hormone replacement therapy. In this study, we report the release and isolation of an estrogen receptor agonist from osteoblast cultures. This entity reprises many aspects of estradiol activity in isolated osteoblasts, but differs from authentic estradiol by several biochemical and physical criteria. At levels that occur in conditioned medium from differentiating osteoblast cultures, the agonist directly drives gene expression through estrogen-sensitive response elements, activates the obligate osteoblast transcription factor Runx2, and potently enhances Smad-dependent gene expression in response to TGF-␤, but exhibits relatively lesser suppressive effects on gene expression through C/EBP and AP-1-binding protein transcription factors. Estrogen receptor agonist activity is resistant to heating at 100°C and separable from the bulk of the remaining alcohol-and hexane-soluble molecules by C18 chromatography. MS and molecular fragmentation analyses predict a Mr of 415.2 to 437.2. Therefore, in addition to earlier studies showing that osteoblasts readily respond to and metabolize various sex steroid-like substrates, we find that they also generate a potent estrogen receptor agonist during differentiation in vitro. Changes in the availability of a molecule like this within bone may relate to differences in skeletal integrity with aging or metabolic disease.intracrine ͉ selective estrogen receptor modulator ͉ steroid S ex steroids cause direct genomic transcriptional effects through specific receptors that contain ligand binding, dimerization, DNA binding, and gene transactivation domains. They also cause indirect stimulatory or inhibitory effects through complexes composed of activated hormone receptor and other transcription factors or through variations in the activation potential of other transcriptional components (1-6) The skeleton is a well recognized target for sex steroids. Bone fragility is notable when sex steroid levels fall in women after menopause, in elderly males, or after sex organ ablation (7-11). In such cases, bone loss follows a release from native constraints on bone resorption that largely result from changes in growth regulators expressed by osteoblasts and from opposing effects on osteoblast and osteoclast activation and apoptosis, leading to an overall increase in bone remodeling (12-16). Importantly, imbalances in bone remodeling are restored by sex hormone replacement therapy. Regardless of a clear benefit for bone, use of native sex steroids risks inappropriate gene activation in other tissues. The possibility of breast, cardiovascular, and prostate disease that can occur in this context (17-19) has driven the search for sex hormone receptor modulators with tissue-or function-restricted effects. However, the value of agents like these may be complicated by steroid and precursor metabolizing enzymes expressed by osteoblasts (3,20,21).Many cells u...

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Section: Discussionmentioning

confidence: 99%

Expression of an estrogen receptor agonist in differentiating osteoblast cultures

McCarthy

Clough²,

Gundberg³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…This is in accordance with the experience of others (39), who found a decrease in IGF-I in postmenopausal women after oral, but not transdermal, oestrogens. A decrease in IGF-I was also observed after combined oral contraceptive use in women of fertile age (40,41).…”

Section: Discussionmentioning

confidence: 83%

Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome

Vrbíková

Stanická²,

Dvořáková³

et al. 2004

European Journal of Endocrinology

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Objective: To compare the influence of transdermal and peroral oestrogen treatments in conjunction with cyproterone acetate (CPA) on metabolic and hormonal parameters in women with polycystic ovary syndrome (PCOS). Patients and methods: Twenty-four women with PCOS, aged 25.4^4.3 (mean^S.D.) years, body mass index 24.5^3.9 kg/m 2 were randomly assigned to receive either transdermal oestradiol plus CPA (n ¼ 12) or a peroral oestradiol -CPA combination (n ¼ 12). Before and after 3 months of treatment, basal blood samples, euglycaemic hyperinsulinaemic clamp combined with indirect calorimetry and arginine tests were performed. ANOVA and Student's t-test or Wilcoxon's test were used for statistical analyses. Results: After peroral oestradiol -CPA, insulin sensitivity (P , 0.004) and the disposition index as the function of insulin sensitivity and secretion (P , 0.0001) decreased significantly. Fasting insulin (P , 0.05), cholesterol (P , 0.05), high-density lipoprotein cholesterol (P , 0.05) and sex-hormone binding globulin (P , 0.0001) increased significantly. Dehydroepiandrosterone (P , 0.05) and 17-OH progesterone (P , 0.01) decreased significantly. After transdermal oestradiol þ CPA, no significant changes were observed in sex-hormone binding globulin and androgen concentrations, insulin sensitivity or disposition index. Conclusions: In women with PCOS, peroral oestrogens (at doses common in combined oral contraceptives) led to a significant impairment in insulin secretion and action. In contrast, the transdermal application of oestrogens did not significantly influence insulin sensitivity. 150 215-223 European Journal of Endocrinology

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“…A recent meta-analysis showed that OC use reduced free testosterone by 61% compared to non-users 44 , possibly due to an increase in sex hormone binding globulin concentration, which binds to testosterone rendering it inactive. OC use increases GH concentrations [45][46] with second (30 µg EE and 0.125 mg Levonorgestrel) and fourth generation (30 µg EE and 2 mg Dienogest) OCs reducing concentrations of IGF-1, but not a ecting IGF binding protein-1 concentrations 45 . e generation of contraceptive in uences the response of IGF-1; 30% reduction following fourth generation OC use compared to 12% reduction following second generation use 46 , possibly as the androgenic Levonorgestrel opposes the e ects of oestrogen on IGF-1 concentrations.…”

Section: Is There a Relationship Between Hormonal Contraceptives And mentioning

confidence: 99%

A perspective on current research investigating the effects of hormonal contraceptives on determinants of female athlete performance

Martín

Elliott‐Sale

2016

Rev. bras. educ. fís. esporte

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Effects of two oral contraceptives on plasma levels of insulin-like growth factor I (IGF-I) and growth hormone (hGH)

Cited by 39 publications

References 30 publications

Expression of an estrogen receptor agonist in differentiating osteoblast cultures

Expression of an estrogen receptor agonist in differentiating osteoblast cultures

Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome

A perspective on current research investigating the effects of hormonal contraceptives on determinants of female athlete performance

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