Thyroid hormone inhibits the human prolactin gene promoter by interfering with activating protein-1 and estrogen stimulations

Molecular Endocrinology
F PernasettiM Muller

Abstract

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.

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Citations

Feb 18, 2006·Journal of Endocrinological Investigation·A R AngioniA Spada
Mar 5, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ana B F Emiliano, Julie L Fudge
Feb 3, 2012·Physiological Reviews·Carolina Perez-CastroEduardo Arzt
Sep 14, 1999·The American Journal of Physiology·R C PereiraE Canalis
Apr 13, 2019·Molecular Diagnosis & Therapy·Paola ConcolinoRosa Maria Paragliola
Sep 12, 2002·The Journal of Biological Chemistry·Marie-Hélène QuentienIsabelle Pellegrini
Jun 23, 2005·Domestic Animal Endocrinology·Yong LiangXiquan Zhang

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