Growth hormone regulates growth hormone receptor gene transcription in primary human thyroid cells

Mol Cell Endocrinol. 2000 Aug 30;166(2):111-9. doi: 10.1016/s0303-7207(00)00272-0.

Abstract

In this study the regulation of GH-receptor gene (GHR/GHBP) transcription by different concentrations of GH (0, 12.5, 25, 50, 150, 500 ng/ml) with and without variable TSH concentrations (0.5, 2, 20 mU/l) in primary human thyroid cells cultured in serum-free hormonally-defined medium was studied. The incubation time was 6 h and GHR/GHBP mRNA expression was quantitatively assessed by using PCR amplification at hourly intervals. Correlating with the GH-concentrations added a constant and significant increase of GHR/GHBP gene transcription was found. After the addition of 12.5 ng/ml GH, GHR/GHBP mRNA concentration remained constant over the incubation period of 6 h but in comparison with the experiments where no GH was added there was a significant change of GHR/GHBP mRNA expression. Following the addition of 25 ng/ml GH a slight but further increase of GHR/GHBP transcription products was seen which increased even more in the experiments where higher GH concentrations were used. These data focusing on GHR/GHBP gene transcription derived from cDNA synthesis and quantitative PCR amplification were confirmed by run-on experiments. Furthermore, cycloheximide did not affect these changes supporting the notion that GH stimulates GHR/GHBP gene transcription directly. In a second set of experiments, in combination with variable TSH levels, identical GH concentrations were used and no difference in either GHR/GHBP mRNA levels or in transcription rate (run-on experiments) could be found. In conclusion, we report data showing that primary thyroid cells express functional GH-receptors in which GH has a direct and dose dependent effect on the GHR/GHBP gene transcription. Furthermore, TSH does not a have a major impact on GHR/GHBP gene regulation.

MeSH terms

  • Base Sequence
  • Carrier Proteins / genetics
  • Cells, Cultured
  • DNA Primers / genetics
  • Dose-Response Relationship, Drug
  • Human Growth Hormone / administration & dosage
  • Human Growth Hormone / pharmacology*
  • Humans
  • Kinetics
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Somatotropin / genetics*
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism*
  • Thyrotropin / administration & dosage
  • Transcription, Genetic / drug effects

Substances

  • Carrier Proteins
  • DNA Primers
  • RNA, Messenger
  • Receptors, Somatotropin
  • Human Growth Hormone
  • Thyrotropin
  • somatotropin-binding protein