Sp1 and thyroid hormone receptor differentially activate expression of human growth hormone and chorionic somatomammotropin genes

J Biol Chem. 1991 May 25;266(15):9805-13.


Activation of hGH-1 expression is mediated by the pituitary-specific transcription factor GHF-I/Pit-I which binds the 5'-flanking DNA at two sites: I (-96/-70) and II (-134/-106). Although the factor(s) which direct the placental-specific expression of hCS-1 are not known, hCS-1 sequences are transcriptionally active in pituitary cells. In the present study we examined the effects of sequence differences between hGH-1 and hCS-1 5'-flanking DNAs in determining their basal and thyroid hormone-regulated promoter activities. We showed that Sp1 is a major determinant of both hGH-1 and hCS-1 promoter activities and that in hGH-1, binding and activation by Sp1 are modulated by interference from GHF-I/Pit-1 binding at the adjacent site II sequence. A single base which differed in site II of hCS-1 greatly reduced GHF-1/Pit-1 binding and thus facilitated binding and activation by Sp1. Further differences in promoter activity of hGH-1 and hCS-1 sequences were accounted for by a thyroid hormone-responsive element between -62/-48 in the hCS-1 gene. However, induction by T3 was independent of either Sp1 or GH-1/Pit-1 binding in the site II region. These data demonstrate that a small number of base changes between hGH and hCS promoter sequences subserve a number of mechanisms which may differentially modulate the expression of hGH and hCS genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chloramphenicol O-Acetyltransferase / genetics
  • DNA Fingerprinting
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Growth Hormone / genetics*
  • Humans
  • Methylation
  • Molecular Sequence Data
  • Placental Lactogen / genetics*
  • Plasmids
  • Receptors, Thyroid Hormone / metabolism*
  • Sp1 Transcription Factor / metabolism*
  • Thyroid Hormones / pharmacology
  • Transcription Factor Pit-1
  • Transcription Factors / metabolism
  • Transfection


  • DNA-Binding Proteins
  • POU1F1 protein, human
  • Receptors, Thyroid Hormone
  • Sp1 Transcription Factor
  • Thyroid Hormones
  • Transcription Factor Pit-1
  • Transcription Factors
  • Growth Hormone
  • Placental Lactogen
  • Chloramphenicol O-Acetyltransferase

Associated data

  • GENBANK/M03833
  • GENBANK/M05622