title: Family members CREB and CREM control thyrotropin-releasing hormone (TRH) expression in the hypothalamus.
abstract: Thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the hypothalamus is regulated by thyroid hormone (TH). cAMP response element binding protein (CREB) has also been postulated to regulate TRH expression but its interaction with TH signaling in vivo is not known. To evaluate the role of CREB in TRH regulation in vivo, we deleted CREB from PVN neurons to generate the CREB1(ΔSIM1) mouse. As previously shown, loss of CREB was compensated for by an up-regulation of CREM in euthyroid CREB1(ΔSIM1) mice but TSH, T₄ and T₃ levels were normal, even though TRH mRNA levels were elevated. Interestingly, TRH mRNA expression was also increased in the PVN of CREB1(ΔSIM1) mice in the hypothyroid state but became normal when made hyperthyroid. Importantly, CREM levels were similar in CREB1(ΔSIM1) mice regardless of thyroid status, demonstrating that the regulation of TRH by T₃ in vivo likely occurs independently of the CREB/CREM family.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Center of Life Science, Boston, MA 02215, United States. franck.chiappini@inserm.fr
authors.forename: Franck
authors.initials: F
authors.lastname: Chiappini
authors.forename: Preeti
authors.initials: P
authors.lastname: Ramadoss
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Vella
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Cunha
authors.forename: Felix D
authors.initials: FD
authors.lastname: Ye
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Stuart
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Nillni
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Hollenberg
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D013973:Thyrotropin-Releasing Hormone; D014284:Triiodothyronine; C492004:Creb1 protein, mouse; C497411:Crem protein, mouse; C101750:Sim1 protein, mouse