title: Starvation-induced changes in the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA and the hypothalamic release of proTRH-derived peptides: role of the adrenal gland.
abstract: The purpose of this study was to investigate the mechanisms involved in the reduced thyroid function in starved, young female rats. Food deprivation for 3 days reduced the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA, the amount of proTRH-derived peptides (TRH and proTRH160-169) in the paraventricular nucleus, the release of proTRH-derived peptides into hypophysial portal blood and the pituitary levels of TSH beta mRNA. Plasma TSH was either not affected or slightly reduced by starvation, but food deprivation induced marked increases in plasma corticosterone and decreases in plasma thyroid hormones. Refeeding after starvation normalized these parameters. Since the molar ratio of TRH and proTRH160-169 in hypophysial portal blood was not affected by food deprivation, it seems unlikely that proTRH processing is altered by starvation. The median eminence content of pGlu-His-Pro-Gly (TRH-Gly, a presumed immediate precursor of TRH), proTRH160-169 or TRH were not affected by food deprivation. Since median eminence TRH-Gly levels were very low compared with other proTRH-derived peptides it is unlikely that alpha-amidation is a rate-limiting step in hypothalamic TRH synthesis. Possible negative effects of the increased corticosterone levels during starvation on proTRH and TSH synthesis were studied in adrenalectomized rats which were treated with corticosterone in their drinking water (0.2 mg/ml). In this way, the starvation-induced increase in plasma corticosterone could be prevented. Although plasma levels of thyroid hormones remained reduced, food deprivation no longer had negative effects on hypothalamic proTRH mRNA, pituitary TSH beta mRNA and plasma TSH in starved adrenalectomized rats. Thus, high levels of corticosteroids seem to exert negative effects on the synthesis and release of proTRH and TSH. This conclusion is corroborated by the observation that TRH release into hypophysial portal blood became reduced after administration of the synthetic glucocorticosteroid dexamethasone. On the basis of these results, it is suggested that the reduced thyroid function during starvation is due to a reduced synthesis and release of TRH and TSH. Furthermore, the reduced TRH and TSH synthesis during food deprivation are probably caused by the starvation-induced enhanced adrenal secretion of corticosterone.
authors.affiliation: Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, The Netherlands.
authors.forename: G A
authors.initials: GA
authors.lastname: van Haasteren
authors.forename: E
authors.initials: E
authors.lastname: Linkels
authors.forename: W
authors.initials: W
authors.lastname: Klootwijk
authors.forename: H
authors.initials: H
authors.lastname: van Toor
authors.forename: J M
authors.initials: JM
authors.lastname: Rondeel
authors.forename: A P
authors.initials: AP
authors.lastname: Themmen
authors.forename: F H
authors.initials: FH
authors.lastname: de Jong
authors.forename: K
authors.initials: K
authors.lastname: Valentijn
authors.forename: H
authors.initials: H
authors.lastname: Vaudry
authors.forename: K
authors.initials: K
authors.lastname: Bauer
mesh_terms: D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D015152:Blotting, Northern; D003345:Corticosterone / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D017403:In Situ Hybridization; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D013972:Thyrotropin; C046418:pro-thyrotropin releasing hormone; D011761:Pyrrolidonecarboxylic Acid; D003345:Corticosterone