Regulation of human growth hormone receptor gene transcription by triiodothyronine (T3)

Mullis, PE; Eblé, A; Marti, U; Bürgi, U; Postel-Vinay, MC (1999). Regulation of human growth hormone receptor gene transcription by triiodothyronine (T3). Molecular and cellular endocrinology, 147(1-2), pp. 17-25. Shannon: Elsevier Ireland 10.1016/S0303-7207(98)00232-9

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In this study the hypothesis that triiodothyronine (T3) and growth hormone (GH) may have some direct or indirect effect on the regulation of GH-receptor/GH-binding protein (GHR/GHBP) gene transcription was tested. Different concentrations of T3 (0, 0.5, 2, 10 nmol/l) and GH (0, 10, 150 ng/ml) were added to human hepatoma (HuH7) cells cultured in serum-free hormonally-defined medium for 0, 1 and 2 h. Thereafter GHR/GHBP mRNA expression was quantitatively assessed by using PCR amplification. GH at a concentration of 10 ng/ml resulted in a significant increase of GHR/GHBP gene expression whereas a supraphysiological concentration of GH (150 ng/ml) caused a significant decrease of GHR/GHBP mRNA levels. The simultaneous addition of 0.5 nmol/l T3 to the variable concentrations of GH did not modify GHR/GHBP mRNA levels whereas the addition of 2 nmol/l up-regulated GHR/GHBP gene expression already after 1 h, an increase which was even more marked when 10 nmol/l of T3 was added. Interestingly, there was a positive correlation between the increase of GHR/GHBP mRNA levels and the T3 concentration used (r: 0.8). In addition, nuclear run-on experiments and GHBP determinations were performed which confirmed the changes in GHR/GHBP mRNA levels. Cycloheximide (10 microg/ml) did not alter transcription rate following GH addition but blocked GHR/GHBP gene transcription in T3 treated cells indicating that up-regulation of GHR/GHBP gene transcription caused by T3 requires new protein synthesis and is, therefore, dependent on indirect mechanisms. In conclusion, we present data showing that T3 on its own has a stimulatory effect on GHR/GHBP gene transcription which is indirect and additive to the GH-induced changes.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine

UniBE Contributor:

Bürgi, Ulrich

ISSN:

0303-7207

ISBN:

10195688

Publisher:

Elsevier Ireland

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:01

Last Modified:

17 Mar 2015 22:13

Publisher DOI:

10.1016/S0303-7207(98)00232-9

PubMed ID:

10195688

Web of Science ID:

000078765400003

URI:

https://boris.unibe.ch/id/eprint/26585 (FactScience: 73547)

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