Differential effects of androgens and estrogens over cellular GH sensitivity in HEPG2 cells
Copyright © 2021 Elsevier Ltd. All rights reserved..
Testosterone and estrogen concentrations progressively increase during puberty, and in association with growth hormone (GH), lead to the increase in height velocity known as the pubertal growth spurt. Very limited information is available however, regarding the possible effects of sex steroids over GH cellular sensitivity.
OBJECTIVE: To investigate the effects of different concentrations of testosterone, estradiol and dihydrotestosterone over the GH intracellular signaling pathway.
METHODS: We evaluated the effects of these sex steroids on the nuclear phosphorylation of STAT5b and IGF-1 expression, in HEPG2 human hepatoma cells. In addition, we studied whether Tamoxifen (TAM), can modulate these effects.
RESULTS: The highest concentration of T tested (10 ng/mL) co-incubated with a fixed concentration of GH (40 ng/mL) increased nuclear STAT5b phosphorylation compared with GH alone (1.34 ± 0.2 vs 0.6 ± 0.09 AU; *p < 0.05), as well as IGF-1 expression (0.6 ± 0.03 vs 0.32 ± 0.05 AU; *p < 0.05). This effect was not observed with lower concentrations of T tested (1 and 5 ng/mL). A similar increase in nuclear STAT5b phosphorylation was observed with the lowest concentration of E2 tested (20 pg/mL), co-incubated with the same fixed concentration of GH (3.6 ± 0.5 vs 1.28 ± 0.33 AU; *p < 0.05). This effect was also associated with an increase in IGF-1 expression (0.73 ± 0.02 vs 0.39 ± 0.04 AU; *p < 0.05). These results were not observed with higher concentrations of E2 tested (75 and 200 pg/mL). DHT at concentrations of 0.1, 0.25 and 0.5 ng/mL, co-stimulated with GH, did not change cytoplasmic STAT5b phosphorylation, nuclear STAT5b or IGF-1 expression. In addition, the co-incubation of TAM with the highest concentration of T tested (10 ng/mL) and GH (40 ng/mL) did not change cytoplasmic, nuclear pSTAT5 levels or IGF-1 expression.
CONCLUSIONS: T and E2 potentiate the GH signaling pathway in a concentration-dependent fashion. The observation that the non-aromatizable androgen dihydrotestosterone does not stimulate this pathway, and that the effects of T are blocked with TAM, suggests that the effects of T over the GH signaling pathway appear to be mediated by estrogen.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:57-58 |
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| Enthalten in: |
Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society - 57-58(2021) vom: 15. Apr., Seite 101390 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ocaranza, Paula [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.02.2022 Date Revised 09.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ghir.2021.101390 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Ocaranza, Paula |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Differential effects of androgens and estrogens over cellular GH sensitivity in HEPG2 cells |
| 264 | 1 | |c 2021 | |
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| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 09.02.2022 | ||
| 500 | |a Date Revised 09.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Testosterone and estrogen concentrations progressively increase during puberty, and in association with growth hormone (GH), lead to the increase in height velocity known as the pubertal growth spurt. Very limited information is available however, regarding the possible effects of sex steroids over GH cellular sensitivity | ||
| 520 | |a OBJECTIVE: To investigate the effects of different concentrations of testosterone, estradiol and dihydrotestosterone over the GH intracellular signaling pathway | ||
| 520 | |a METHODS: We evaluated the effects of these sex steroids on the nuclear phosphorylation of STAT5b and IGF-1 expression, in HEPG2 human hepatoma cells. In addition, we studied whether Tamoxifen (TAM), can modulate these effects | ||
| 520 | |a RESULTS: The highest concentration of T tested (10 ng/mL) co-incubated with a fixed concentration of GH (40 ng/mL) increased nuclear STAT5b phosphorylation compared with GH alone (1.34 ± 0.2 vs 0.6 ± 0.09 AU; *p < 0.05), as well as IGF-1 expression (0.6 ± 0.03 vs 0.32 ± 0.05 AU; *p < 0.05). This effect was not observed with lower concentrations of T tested (1 and 5 ng/mL). A similar increase in nuclear STAT5b phosphorylation was observed with the lowest concentration of E2 tested (20 pg/mL), co-incubated with the same fixed concentration of GH (3.6 ± 0.5 vs 1.28 ± 0.33 AU; *p < 0.05). This effect was also associated with an increase in IGF-1 expression (0.73 ± 0.02 vs 0.39 ± 0.04 AU; *p < 0.05). These results were not observed with higher concentrations of E2 tested (75 and 200 pg/mL). DHT at concentrations of 0.1, 0.25 and 0.5 ng/mL, co-stimulated with GH, did not change cytoplasmic STAT5b phosphorylation, nuclear STAT5b or IGF-1 expression. In addition, the co-incubation of TAM with the highest concentration of T tested (10 ng/mL) and GH (40 ng/mL) did not change cytoplasmic, nuclear pSTAT5 levels or IGF-1 expression | ||
| 520 | |a CONCLUSIONS: T and E2 potentiate the GH signaling pathway in a concentration-dependent fashion. The observation that the non-aromatizable androgen dihydrotestosterone does not stimulate this pathway, and that the effects of T are blocked with TAM, suggests that the effects of T over the GH signaling pathway appear to be mediated by estrogen | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Dihydrotestosterone | |
| 650 | 4 | |a Estradiol | |
| 650 | 4 | |a GH signal transduction | |
| 650 | 4 | |a Tamoxifen | |
| 650 | 4 | |a Testosterone | |
| 650 | 7 | |a Androgens |2 NLM | |
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| 700 | 1 | |a Íñiguez, Germán |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, M Cecilia |e verfasserin |4 aut | |
| 700 | 1 | |a Cassorla, Fernando |e verfasserin |4 aut | |
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