Abstract
The prohormone convertases (PCs) PC1 and PC2 are key enzymes capable of processing a variety of prohormones to their bioactive forms. In this study, we demonstrated that 6-n-propyl-2-thiouracil (PTU)-induced hypothyroidism stimulated, whereas triido-L-thyronine (T(3))-induced hyperthyroidism suppressed, PC1 mRNA levels in the rat anterior pituitary. Using 5' deletions of the human PC1 (hPC1) promoter transiently transfected into GH3 (a somatotroph cell line) cells, we found that T(3) negatively regulated hPC1 promoter activity and that this regulation required the region from -82 to +19 bp relative to the transcription start site. Electrophoretic mobility shift assays (EMSAs) using purified thyroid hormone receptor-alpha1 (TR alpha 1) and retinoid X receptor-beta (RXRbeta) proteins and GH3 nuclear extracts demonstrated that the region from -10 to +19 bp of the hPC1 promoter bound TR alpha 1 as both a monomer and a homodimer and bound TR alpha 1/RXR beta as a heterodimer and multimer. EMSAs with oligonucleotides containing point mutations of the putative negative thyroid response elements (TREs) exhibited diminished homodimer and loss of multimer binding. We conclude that there are multiple novel TRE-like sequences in the hPC1 promoter located from -10 to +19 bp.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: American journal of physiology. Endocrinology and metabolism
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
