Thyroid hormone inhibits the human prolactin gene promoter by interfering with activating protein-1 and estrogen stimulations.
Transcription of the human PRL (hPRL) gene in the pituitary is subject to tissue-specific and multihormonal regulation involving two main regulatory regions, a proximal promoter and a distal enhancer. In this report we show that thyroid hormone inhibits the expression of the hPRL gene in rat pituitary cells. Transient expression experiments show that thyroid hormone regulation involves a strong inhibitory element, located in the proximal (-164/-35) promoter, which is modulated by a more distal stimulatory response control region. Gel retardation experiments reveal that the thyroid hormone receptor does not bind to the proximal negative element. We show the existence of an activating protein-1 (AP-1) response element located at positions -61 to -54 of the proximal promoter, conferring AP-1 stimulation to the hPRL promoter. This AP-1 induction is abolished when hormone-bound thyroid hormone receptor is present, indicating that there is an interference between the thyroid hormone receptor and AP-1 regulatory pathways. Furthermore, using the complete hPRL upstream region, we show that estrogen induction is abolished by simultaneous thyroid hormone treatment.
Pernasetti
F
F
Laboratoire de Biologie Moléculaire et de Génie Génétique, Université de Liège, Institut de Chimie B6, Sart Tilman, Belgium.
Caccavelli
L
L
Van de Weerdt
C
C
Martial
J A
JA
Muller
M
M
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000187:drug effects / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D012680:Sensitivity and Specificity; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; C494186:Pou1f1 protein, rat; D018808:Transcription Factor AP-1; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D014284:Triiodothyronine; D005576:Colforsin; D004958:Estradiol; D011388:Prolactin