title: Thyroid hormone modulation of TRH precursor levels in rat hypothalamus, pituitary, thyroid and blood.
abstract: In the present study we have examined the in vivo effects of thyroid hormones and TRH on tissue and blood levels of TRH and TRH-Gly (pGlu-His-Pro-Gly), a TRH precursor. Using specific radioimmunoassays (RIAs), we measured TRH immunoreactivity (TRH-IR) and TRH-Gly-IR concentrations in blood, hypothalamus, anterior and posterior pituitary, and thyroid in euthyroid, hypothyroid and thyroxine (T4)-treated 250 g male Sprague-Dawley rats. TRH-Gly-IR and TRH-IR were detected in all of these tissues. Highly significant positive correlations between whole blood TRH-Gly-IR levels and the corresponding serum TSH values (p less than 0.01), whole blood TRH-IR versus serum TSH (p less than 0.01) and whole blood TRH-Gly-IR versus whole blood TRH-IR (p less than 0.01) are consistent with cosecretion of TRH and TRH precursor peptides into the circulation. Euthyroid rats injected with TRH IP (1 microgram/100 g b.wt.) and hypothyroid rats had 4-fold higher whole blood TRH-Gly-IR levels compared to euthyroid controls (p less than 0.0005). Injection of TRH into euthyroid rats significantly increased the TRH-Gly-IR concentration in the hypothalamus, anterior and posterior pituitary and thyroid. The increase in blood TRH-Gly-IR following intravenous TRH may be due, in part, to partial saturation of TRH-degrading enzymes in blood and cell membranes. The ratio of TRH-Gly to TRH was significantly increased in the anterior pituitary by hypothyroidism and TRH injection, suggesting that thyroid hormones and TRH regulate the alpha-amidation of TRH-Gly to form TRH in this tissue. TRH-Gly levels of pooled pituitary and thyroid extracts quantitated by a combination of TRH-Gly RIA and high performance liquid chromatography (HPLC) revealed several-fold increases following incubation at 60 degrees C. Heating at this temperature may block the alpha-amidation activity in extra-hypothalamic tissues but not the "trypsin-like" enzymes which cleave prepro-TRH into TRH-Gly-immunoreactive peptides.
authors.affiliation: Endocrinology Research Laboratory, Veterans Administration Wadsworth Medical Center, Los Angeles, CA 90073.
authors.forename: M
authors.initials: M
authors.lastname: Simard
authors.forename: A E
authors.initials: AE
authors.lastname: Pekary
authors.forename: V P
authors.initials: VP
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Hershman
mesh_terms: D000818:Animals; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007037:Hypothyroidism / Q000097:blood; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood / Q000494:pharmacology*; D014284:Triiodothyronine / Q000097:blood / Q000494:pharmacology*
chemical_list: D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; C040476:thyrotropin-releasing hormone, Gly; D013972:Thyrotropin; D013974:Thyroxine; D011761:Pyrrolidonecarboxylic Acid