Estrogen antagonism on T3 and growth hormone control of the liver microsomal low-affinity glucocorticoid binding site (LAGS)
Male rat liver microsomes contain a low-affinity glucocorticoid binding site (LAGS) capable of binding all natural glucocorticoids and progesterone with a Kd from 20 to 100 nM. The LAGS level is under endocrine control by T3, glucocorticoids and GH. These hormones act synergistically at physiologica...
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description | Male rat liver microsomes contain a low-affinity glucocorticoid binding site (LAGS) capable of binding all natural glucocorticoids and progesterone with a Kd from 20 to 100 nM. The LAGS level is under endocrine control by T3, glucocorticoids and GH. These hormones act synergistically at physiological concentrations to increase the LAGS level. Since female rats show a LAGS level that is much lower than the males (0.15 vs 23 pmol/mg protein, respectively), here we investigated whether estradiol could decrease the LAGS in the male rat. Orchiectomized (OX) male rats showed a higher LAGS level than intact rats. This effect was reversed by implanting a Sylastic capsule containing testosterone. When the OX rats were implanted for 20 days with estrogen capsules that provided an estradiol level in serum of 40 pg/ml, their LAGS level decreased from 23 to 0.2 pmol/mg protein. This effect was not observed in intact male rats and can be partially reversed by testosterone implants into OX rats. Both hypophysectomized male rats and hypothyroid-orchiectomized male rats showed very low levels of LAGS. Administration of physiological doses of GH and/or T3 to these rats greatly increased their LAGS level (from 0.3 to 15 and 16 pmol/mg protein, respectively). Implantation of estrogen capsules to these rats two weeks prior to starting treatment completely inhibited the increase in the LAGS level in response to T3, and significantly decreased the response to hGH, and to a combination of hGH and T3. These results suggest that physiological estradiol levels can antagonize the LAGS induction by T3 and hGH in the male rat, and could be responsible for the low level of LAGS in the female rat. Moreover, estrogen capsules also inhibited the increase in the body and hepatic weights observed after hGH treatment, which suggests a powerful inhibitory effect of low estradiol levels on the male rat liver functions under regulation by T3 and/or GH. |
doi_str_mv | 10.1016/S0960-0760(97)00123-4 |
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D ; ZUMBADO, M ; DIAZ-CHICO, B. N</creator><creatorcontrib>LOPEZ-GUERRA, A ; CHIRINO, R ; NAVARRO, D ; FERNANDEZ, L ; BOADA, L. D ; ZUMBADO, M ; DIAZ-CHICO, B. N</creatorcontrib><description>Male rat liver microsomes contain a low-affinity glucocorticoid binding site (LAGS) capable of binding all natural glucocorticoids and progesterone with a Kd from 20 to 100 nM. The LAGS level is under endocrine control by T3, glucocorticoids and GH. These hormones act synergistically at physiological concentrations to increase the LAGS level. Since female rats show a LAGS level that is much lower than the males (0.15 vs 23 pmol/mg protein, respectively), here we investigated whether estradiol could decrease the LAGS in the male rat. Orchiectomized (OX) male rats showed a higher LAGS level than intact rats. This effect was reversed by implanting a Sylastic capsule containing testosterone. When the OX rats were implanted for 20 days with estrogen capsules that provided an estradiol level in serum of 40 pg/ml, their LAGS level decreased from 23 to 0.2 pmol/mg protein. This effect was not observed in intact male rats and can be partially reversed by testosterone implants into OX rats. Both hypophysectomized male rats and hypothyroid-orchiectomized male rats showed very low levels of LAGS. Administration of physiological doses of GH and/or T3 to these rats greatly increased their LAGS level (from 0.3 to 15 and 16 pmol/mg protein, respectively). Implantation of estrogen capsules to these rats two weeks prior to starting treatment completely inhibited the increase in the LAGS level in response to T3, and significantly decreased the response to hGH, and to a combination of hGH and T3. These results suggest that physiological estradiol levels can antagonize the LAGS induction by T3 and hGH in the male rat, and could be responsible for the low level of LAGS in the female rat. Moreover, estrogen capsules also inhibited the increase in the body and hepatic weights observed after hGH treatment, which suggests a powerful inhibitory effect of low estradiol levels on the male rat liver functions under regulation by T3 and/or GH.</description><identifier>ISSN: 0960-0760</identifier><identifier>EISSN: 1879-1220</identifier><identifier>DOI: 10.1016/S0960-0760(97)00123-4</identifier><identifier>PMID: 9459188</identifier><language>eng</language><publisher>Oxford: Elsevier Science</publisher><subject>Animals ; Binding Sites ; Biological and medical sciences ; Estrogen Antagonists - pharmacology ; Estrogens - physiology ; Female ; Fundamental and applied biological sciences. Psychology ; Glucocorticoids - metabolism ; Growth Hormone - antagonists & inhibitors ; Growth Hormone - physiology ; Humans ; Hypophysectomy ; Male ; Microsomes, Liver - metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Steroid hormones. Cholecalciferol derivatives ; Tamoxifen - pharmacology ; Triiodothyronine - antagonists & inhibitors ; Triiodothyronine - physiology ; Vertebrates: endocrinology</subject><ispartof>The Journal of steroid biochemistry and molecular biology, 1997-11, Vol.63 (4-6), p.219-228</ispartof><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c248t-e8f53d315ddc01e326138e91f352b73d3906dc9b6f5238fe6fde0fd4b4076af33</citedby><cites>FETCH-LOGICAL-c248t-e8f53d315ddc01e326138e91f352b73d3906dc9b6f5238fe6fde0fd4b4076af33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2111510$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9459188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LOPEZ-GUERRA, A</creatorcontrib><creatorcontrib>CHIRINO, R</creatorcontrib><creatorcontrib>NAVARRO, D</creatorcontrib><creatorcontrib>FERNANDEZ, L</creatorcontrib><creatorcontrib>BOADA, L. D</creatorcontrib><creatorcontrib>ZUMBADO, M</creatorcontrib><creatorcontrib>DIAZ-CHICO, B. N</creatorcontrib><title>Estrogen antagonism on T3 and growth hormone control of the liver microsomal low-affinity glucocorticoid binding site (LAGS)</title><title>The Journal of steroid biochemistry and molecular biology</title><addtitle>J Steroid Biochem Mol Biol</addtitle><description>Male rat liver microsomes contain a low-affinity glucocorticoid binding site (LAGS) capable of binding all natural glucocorticoids and progesterone with a Kd from 20 to 100 nM. The LAGS level is under endocrine control by T3, glucocorticoids and GH. These hormones act synergistically at physiological concentrations to increase the LAGS level. Since female rats show a LAGS level that is much lower than the males (0.15 vs 23 pmol/mg protein, respectively), here we investigated whether estradiol could decrease the LAGS in the male rat. Orchiectomized (OX) male rats showed a higher LAGS level than intact rats. This effect was reversed by implanting a Sylastic capsule containing testosterone. When the OX rats were implanted for 20 days with estrogen capsules that provided an estradiol level in serum of 40 pg/ml, their LAGS level decreased from 23 to 0.2 pmol/mg protein. This effect was not observed in intact male rats and can be partially reversed by testosterone implants into OX rats. Both hypophysectomized male rats and hypothyroid-orchiectomized male rats showed very low levels of LAGS. Administration of physiological doses of GH and/or T3 to these rats greatly increased their LAGS level (from 0.3 to 15 and 16 pmol/mg protein, respectively). Implantation of estrogen capsules to these rats two weeks prior to starting treatment completely inhibited the increase in the LAGS level in response to T3, and significantly decreased the response to hGH, and to a combination of hGH and T3. These results suggest that physiological estradiol levels can antagonize the LAGS induction by T3 and hGH in the male rat, and could be responsible for the low level of LAGS in the female rat. Moreover, estrogen capsules also inhibited the increase in the body and hepatic weights observed after hGH treatment, which suggests a powerful inhibitory effect of low estradiol levels on the male rat liver functions under regulation by T3 and/or GH.</description><subject>Animals</subject><subject>Binding Sites</subject><subject>Biological and medical sciences</subject><subject>Estrogen Antagonists - pharmacology</subject><subject>Estrogens - physiology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glucocorticoids - metabolism</subject><subject>Growth Hormone - antagonists & inhibitors</subject><subject>Growth Hormone - physiology</subject><subject>Humans</subject><subject>Hypophysectomy</subject><subject>Male</subject><subject>Microsomes, Liver - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rats, Wistar</subject><subject>Steroid hormones. Cholecalciferol derivatives</subject><subject>Tamoxifen - pharmacology</subject><subject>Triiodothyronine - antagonists & inhibitors</subject><subject>Triiodothyronine - physiology</subject><subject>Vertebrates: endocrinology</subject><issn>0960-0760</issn><issn>1879-1220</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1LJDEQhsPiorO6P0HIQUQP7VaS_spRxFVhwIN6Dul89ETSiSYZB2F__PboMKeCep-qoh6ETglcESDtnyfgLVTQtXDBu0sAQllV_0AL0ne8IpTCAVrskSP0K-dXAGCMdIfokNcNJ32_QP9uc0lxNAHLUOQYg8sTjgE_s7mh8ZjipqzwKqYpBoNVDDPtcbS4rAz27sMkPDmVYo6T9NjHTSWtdcGVTzz6tYoqpuJUdBoPLmgXRpxdMfhieX33dHmCflrps_m9q8fo5e_t8819tXy8e7i5XlaK1n2pTG8bphlptFZADKMtYb3hxLKGDt2ccGi14kNrG8p6a1qrDVhdD_X8urSMHaPz771vKb6vTS5iclkZ72UwcZ1Fx5ua9m09g803uP0oJ2PFW3KTTJ-CgNhaF1_WxVap4J34si62c6e7A-thMno_tdM852e7XGYlvU0yKJf3GCWENATYf29Ri6E</recordid><startdate>199711</startdate><enddate>199711</enddate><creator>LOPEZ-GUERRA, A</creator><creator>CHIRINO, R</creator><creator>NAVARRO, D</creator><creator>FERNANDEZ, L</creator><creator>BOADA, L. D</creator><creator>ZUMBADO, M</creator><creator>DIAZ-CHICO, B. N</creator><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>7X8</scope></search><sort><creationdate>199711</creationdate><title>Estrogen antagonism on T3 and growth hormone control of the liver microsomal low-affinity glucocorticoid binding site (LAGS)</title><author>LOPEZ-GUERRA, A ; CHIRINO, R ; NAVARRO, D ; FERNANDEZ, L ; BOADA, L. D ; ZUMBADO, M ; DIAZ-CHICO, B. N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c248t-e8f53d315ddc01e326138e91f352b73d3906dc9b6f5238fe6fde0fd4b4076af33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Binding Sites</topic><topic>Biological and medical sciences</topic><topic>Estrogen Antagonists - pharmacology</topic><topic>Estrogens - physiology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glucocorticoids - metabolism</topic><topic>Growth Hormone - antagonists & inhibitors</topic><topic>Growth Hormone - physiology</topic><topic>Humans</topic><topic>Hypophysectomy</topic><topic>Male</topic><topic>Microsomes, Liver - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rats, Wistar</topic><topic>Steroid hormones. Cholecalciferol derivatives</topic><topic>Tamoxifen - pharmacology</topic><topic>Triiodothyronine - antagonists & inhibitors</topic><topic>Triiodothyronine - physiology</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LOPEZ-GUERRA, A</creatorcontrib><creatorcontrib>CHIRINO, R</creatorcontrib><creatorcontrib>NAVARRO, D</creatorcontrib><creatorcontrib>FERNANDEZ, L</creatorcontrib><creatorcontrib>BOADA, L. D</creatorcontrib><creatorcontrib>ZUMBADO, M</creatorcontrib><creatorcontrib>DIAZ-CHICO, B. 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N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estrogen antagonism on T3 and growth hormone control of the liver microsomal low-affinity glucocorticoid binding site (LAGS)</atitle><jtitle>The Journal of steroid biochemistry and molecular biology</jtitle><addtitle>J Steroid Biochem Mol Biol</addtitle><date>1997-11</date><risdate>1997</risdate><volume>63</volume><issue>4-6</issue><spage>219</spage><epage>228</epage><pages>219-228</pages><issn>0960-0760</issn><eissn>1879-1220</eissn><abstract>Male rat liver microsomes contain a low-affinity glucocorticoid binding site (LAGS) capable of binding all natural glucocorticoids and progesterone with a Kd from 20 to 100 nM. The LAGS level is under endocrine control by T3, glucocorticoids and GH. These hormones act synergistically at physiological concentrations to increase the LAGS level. Since female rats show a LAGS level that is much lower than the males (0.15 vs 23 pmol/mg protein, respectively), here we investigated whether estradiol could decrease the LAGS in the male rat. Orchiectomized (OX) male rats showed a higher LAGS level than intact rats. This effect was reversed by implanting a Sylastic capsule containing testosterone. When the OX rats were implanted for 20 days with estrogen capsules that provided an estradiol level in serum of 40 pg/ml, their LAGS level decreased from 23 to 0.2 pmol/mg protein. This effect was not observed in intact male rats and can be partially reversed by testosterone implants into OX rats. Both hypophysectomized male rats and hypothyroid-orchiectomized male rats showed very low levels of LAGS. Administration of physiological doses of GH and/or T3 to these rats greatly increased their LAGS level (from 0.3 to 15 and 16 pmol/mg protein, respectively). Implantation of estrogen capsules to these rats two weeks prior to starting treatment completely inhibited the increase in the LAGS level in response to T3, and significantly decreased the response to hGH, and to a combination of hGH and T3. These results suggest that physiological estradiol levels can antagonize the LAGS induction by T3 and hGH in the male rat, and could be responsible for the low level of LAGS in the female rat. Moreover, estrogen capsules also inhibited the increase in the body and hepatic weights observed after hGH treatment, which suggests a powerful inhibitory effect of low estradiol levels on the male rat liver functions under regulation by T3 and/or GH.</abstract><cop>Oxford</cop><pub>Elsevier Science</pub><pmid>9459188</pmid><doi>10.1016/S0960-0760(97)00123-4</doi><tpages>10</tpages></addata></record> |
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subjects | Animals Binding Sites Biological and medical sciences Estrogen Antagonists - pharmacology Estrogens - physiology Female Fundamental and applied biological sciences. Psychology Glucocorticoids - metabolism Growth Hormone - antagonists & inhibitors Growth Hormone - physiology Humans Hypophysectomy Male Microsomes, Liver - metabolism Rats Rats, Sprague-Dawley Rats, Wistar Steroid hormones. Cholecalciferol derivatives Tamoxifen - pharmacology Triiodothyronine - antagonists & inhibitors Triiodothyronine - physiology Vertebrates: endocrinology |
title | Estrogen antagonism on T3 and growth hormone control of the liver microsomal low-affinity glucocorticoid binding site (LAGS) |
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