PMID- 12970166 OWN - NLM STAT- MEDLINE DCOM- 20040105 LR - 20141120 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 144 IP - 12 DP - 2003 Dec TI - Corticotropin-releasing hormone (CRH)-induced thyrotropin release is directly mediated through CRH receptor type 2 on thyrotropes. PG - 5537-44 AB - CRH is known as the main stimulator of ACTH release. In representatives of all nonmammalian vertebrates, CRH has also been shown to induce TSH secretion, acting directly at the level of the pituitary. We have investigated which cell types and receptors are involved in CRH-induced TSH release in the chicken (Gallus gallus). Because a lack of CRH type 1 receptors (CRH-R1) on the chicken thyrotropes has been previously reported, two hypotheses were tested using in situ hybridization and perifusion studies: 1) TSH secretion might be induced in a paracrine way involving melanocortins from the corticotropes; and 2) thyrotropes might express another type of CRH-R. For the latter, we have cloned a partial cDNA encoding the chicken CRH-R2. Neither alpha-melanotropin (alpha-MSH) nor its powerful analog Nle4,d-Phe7-MSH could mimic the in vitro TSH-releasing effect of ovine CRH. The nonselective melanocortin receptor blocker SHU91199 did not influence CRH- or TRH-induced TSH secretion. On the other hand, we have found that thyrotropes express CRH-R2 mRNA. The involvement of this CRH receptor in the response of thyrotropes to CRH was further confirmed by the fact that TSH release was stimulated by human urocortin III, a CRH-R2-specific agonist, whereas the TSH response to CRH was completely blocked by the CRH-R blocker astressin and the CRH-R2-specific antagonist antisauvagine-30. We conclude that CRH-induced TSH secretion is mediated by CRH-R2 expressed on thyrotropes. FAU - De Groef, Bert AU - De Groef B AD - Laboratories of Comparative Endocrinology, Catholic University of Leuven, Leuven, Belgium. bert.degroef@bio.kuleuven.ac.be. FAU - Goris, Nesya AU - Goris N FAU - Arckens, Lutgarde AU - Arckens L FAU - Kuhn, Eduard R AU - Kuhn ER FAU - Darras, Veerle M AU - Darras VM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030911 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (DNA, Complementary) RN - 0 (Neuroprotective Agents) RN - 0 (Peptide Fragments) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Corticotropin) RN - 0 (Urocortins) RN - 0 (antisauvagine 30) RN - 170809-51-5 (astressin) RN - 581-05-5 (alpha-MSH) RN - 9002-71-5 (Thyrotropin) RN - 9015-71-8 (Corticotropin-Releasing Hormone) SB - IM MH - Amino Acid Sequence MH - Animals MH - Chickens MH - Cloning, Molecular MH - Corticotropin-Releasing Hormone/*metabolism/pharmacology MH - DNA, Complementary/genetics MH - In Vitro Techniques MH - Molecular Sequence Data MH - Neuroprotective Agents/pharmacology MH - Peptide Fragments/pharmacology MH - Pituitary Gland/physiology MH - RNA, Messenger/analysis MH - Receptors, Corticotropin/antagonists & inhibitors/*genetics/*metabolism MH - Thyrotropin/*metabolism MH - Urocortins MH - alpha-MSH/pharmacology EDAT- 2003/09/13 05:00 MHDA- 2004/01/06 05:00 CRDT- 2003/09/13 05:00 PHST- 2003/09/13 05:00 [pubmed] PHST- 2004/01/06 05:00 [medline] PHST- 2003/09/13 05:00 [entrez] AID - en.2003-0526 [pii] AID - 10.1210/en.2003-0526 [doi] PST - ppublish SO - Endocrinology. 2003 Dec;144(12):5537-44. doi: 10.1210/en.2003-0526. Epub 2003 Sep 11.