Thyroid hormone modulation of TRH precursor levels in rat hypothalamus, pituitary, thyroid and blood

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, hypothal...

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Veröffentlicht in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 1989, Vol.10 (1), p.145-155
Hauptverfasser: Simard, Marie, Pekary, A.Eugene, Smith, Vierka P., Hershman, Jerome M.
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container_issue 1
container_start_page 145
container_title Peptides (New York, N.Y. : 1980)
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creator Simard, Marie
Pekary, A.Eugene
Smith, Vierka P.
Hershman, Jerome M.
description 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
doi_str_mv 10.1016/0196-9781(89)90091-0
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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&lt;0.01), whole blood TRH-IR versus serum TSH ( p&lt;0.01) and whole blood TRH-Gly-IR versus whole blood TRH-IR ( p&lt;0.01) are consistent with cosecretion of TRH and TRH precursor peptides into the circulation. Euthyroid rats injected with TRH IP (1 μg/100 g b.wt.) and hypothyroid rats had 4-fold higher whole blood TRH-Gly-IR levels compared to euthyroid controls ( p&lt;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°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.</description><identifier>ISSN: 0196-9781</identifier><identifier>EISSN: 1873-5169</identifier><identifier>DOI: 10.1016/0196-9781(89)90091-0</identifier><identifier>PMID: 2501768</identifier><identifier>CODEN: PPTDD5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Blood ; Chromatography ; Fundamental and applied biological sciences. Psychology ; General aspects. Hormone interactions. Hormone actions on several organ systems. 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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&lt;0.01), whole blood TRH-IR versus serum TSH ( p&lt;0.01) and whole blood TRH-Gly-IR versus whole blood TRH-IR ( p&lt;0.01) are consistent with cosecretion of TRH and TRH precursor peptides into the circulation. Euthyroid rats injected with TRH IP (1 μg/100 g b.wt.) and hypothyroid rats had 4-fold higher whole blood TRH-Gly-IR levels compared to euthyroid controls ( p&lt;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°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.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Chromatography</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General aspects. Hormone interactions. Hormone actions on several organ systems. Adaptive reactions</subject><subject>Hypothalamus</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - metabolism</subject><subject>Hypothyroidism - blood</subject><subject>Male</subject><subject>Pituitary</subject><subject>Pituitary Gland - drug effects</subject><subject>Pituitary Gland - metabolism</subject><subject>Pyrrolidonecarboxylic Acid - analogs &amp; derivatives</subject><subject>Radioimmunoassay</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Reference Values</subject><subject>Thyroid</subject><subject>Thyroid Gland - drug effects</subject><subject>Thyroid Gland - metabolism</subject><subject>Thyroidectomy</subject><subject>Thyrotropin - blood</subject><subject>Thyrotropin-releasing hormone</subject><subject>Thyrotropin-Releasing Hormone - analogs &amp; derivatives</subject><subject>Thyrotropin-Releasing Hormone - blood</subject><subject>Thyrotropin-Releasing Hormone - metabolism</subject><subject>Thyrotropin-Releasing Hormone - pharmacology</subject><subject>Thyroxine - blood</subject><subject>Thyroxine - pharmacology</subject><subject>Triiodothyronine - blood</subject><subject>Triiodothyronine - pharmacology</subject><subject>Vertebrates: endocrinology</subject><issn>0196-9781</issn><issn>1873-5169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1989</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1rFDEUhoNY6lr9Bwq5EFHoaLLJ5ONGKEVboSDIeh0yyRk2kpmMyUxh_73Z7rCXSi5ycZ7zkjwvQm8o-UQJFZ8J1aLRUtEPSn_UhGjakGdoQ5VkTUuFfo42Z-QFelnKb0II51pdosttS6gUaoP8bn_IKXi8T3lII-Ah-SXaOaQRpx7vft7jKYNbckkZR3iEWHAYcbYz3h-mNO9ttMNSrvEU5iXMNh-u8bxG2tHjLqbkX6GL3sYCr9f7Cv369nV3e988_Lj7fnvz0DhO5dx0qnWqJVwq6CR0vRO6d1JzBkwB64TVvWSt2PYtI-C53CrJe9YxYvUWqJTsCr0_5U45_VmgzGYIxUGMdoS0FCM1UYzW8z-QtlUQk7yC_AS6nErJ0Jsph6H-0lBiji2Yo2JzVGyUNk8tGFLX3q75SzeAPy-t2uv83Tq3xdnYZzu6UM6YqIwUumJfTli1Do8BsikuwOjAh9rJbHwK_37HXxn6o7g</recordid><startdate>1989</startdate><enddate>1989</enddate><creator>Simard, Marie</creator><creator>Pekary, A.Eugene</creator><creator>Smith, Vierka P.</creator><creator>Hershman, Jerome M.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>1989</creationdate><title>Thyroid hormone modulation of TRH precursor levels in rat hypothalamus, pituitary, thyroid and blood</title><author>Simard, Marie ; Pekary, A.Eugene ; Smith, Vierka P. ; Hershman, Jerome M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-b85c850478eb7ebfc69fc7943e38e3b6a9f73562f530ed472874f3b30a92e1773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1989</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Chromatography</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General aspects. Hormone interactions. Hormone actions on several organ systems. Adaptive reactions</topic><topic>Hypothalamus</topic><topic>Hypothalamus - drug effects</topic><topic>Hypothalamus - metabolism</topic><topic>Hypothyroidism - blood</topic><topic>Male</topic><topic>Pituitary</topic><topic>Pituitary Gland - drug effects</topic><topic>Pituitary Gland - metabolism</topic><topic>Pyrrolidonecarboxylic Acid - analogs &amp; derivatives</topic><topic>Radioimmunoassay</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Reference Values</topic><topic>Thyroid</topic><topic>Thyroid Gland - drug effects</topic><topic>Thyroid Gland - metabolism</topic><topic>Thyroidectomy</topic><topic>Thyrotropin - blood</topic><topic>Thyrotropin-releasing hormone</topic><topic>Thyrotropin-Releasing Hormone - analogs &amp; derivatives</topic><topic>Thyrotropin-Releasing Hormone - blood</topic><topic>Thyrotropin-Releasing Hormone - metabolism</topic><topic>Thyrotropin-Releasing Hormone - pharmacology</topic><topic>Thyroxine - blood</topic><topic>Thyroxine - pharmacology</topic><topic>Triiodothyronine - blood</topic><topic>Triiodothyronine - pharmacology</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Simard, Marie</creatorcontrib><creatorcontrib>Pekary, A.Eugene</creatorcontrib><creatorcontrib>Smith, Vierka P.</creatorcontrib><creatorcontrib>Hershman, Jerome M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Peptides (New York, N.Y. : 1980)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Simard, Marie</au><au>Pekary, A.Eugene</au><au>Smith, Vierka P.</au><au>Hershman, Jerome M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thyroid hormone modulation of TRH precursor levels in rat hypothalamus, pituitary, thyroid and blood</atitle><jtitle>Peptides (New York, N.Y. : 1980)</jtitle><addtitle>Peptides</addtitle><date>1989</date><risdate>1989</risdate><volume>10</volume><issue>1</issue><spage>145</spage><epage>155</epage><pages>145-155</pages><issn>0196-9781</issn><eissn>1873-5169</eissn><coden>PPTDD5</coden><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&lt;0.01), whole blood TRH-IR versus serum TSH ( p&lt;0.01) and whole blood TRH-Gly-IR versus whole blood TRH-IR ( p&lt;0.01) are consistent with cosecretion of TRH and TRH precursor peptides into the circulation. Euthyroid rats injected with TRH IP (1 μg/100 g b.wt.) and hypothyroid rats had 4-fold higher whole blood TRH-Gly-IR levels compared to euthyroid controls ( p&lt;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°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.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>2501768</pmid><doi>10.1016/0196-9781(89)90091-0</doi><tpages>11</tpages></addata></record>
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ispartof Peptides (New York, N.Y. : 1980), 1989, Vol.10 (1), p.145-155
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source MEDLINE; Access via ScienceDirect (Elsevier)
subjects Animals
Biological and medical sciences
Blood
Chromatography
Fundamental and applied biological sciences. Psychology
General aspects. Hormone interactions. Hormone actions on several organ systems. Adaptive reactions
Hypothalamus
Hypothalamus - drug effects
Hypothalamus - metabolism
Hypothyroidism - blood
Male
Pituitary
Pituitary Gland - drug effects
Pituitary Gland - metabolism
Pyrrolidonecarboxylic Acid - analogs & derivatives
Radioimmunoassay
Rats
Rats, Inbred Strains
Reference Values
Thyroid
Thyroid Gland - drug effects
Thyroid Gland - metabolism
Thyroidectomy
Thyrotropin - blood
Thyrotropin-releasing hormone
Thyrotropin-Releasing Hormone - analogs & derivatives
Thyrotropin-Releasing Hormone - blood
Thyrotropin-Releasing Hormone - metabolism
Thyrotropin-Releasing Hormone - pharmacology
Thyroxine - blood
Thyroxine - pharmacology
Triiodothyronine - blood
Triiodothyronine - pharmacology
Vertebrates: endocrinology
title Thyroid hormone modulation of TRH precursor levels in rat hypothalamus, pituitary, thyroid and blood
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