In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A

OBJECTIVE Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn‐omas). Since many of the NFAs and Gn‐omas secrete FSH in vitro, we hypothesized...

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Veröffentlicht in:Clinical endocrinology (Oxford) 2001-04, Vol.54 (4), p.485-492
Hauptverfasser: Wessels, H. T., Hofland, L. J., Van Der Wal, R., Van Gastel, L., Van Koetsveld, P. M., De Herder, W. W., De Jong, F. H.
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container_issue 4
container_start_page 485
container_title Clinical endocrinology (Oxford)
container_volume 54
creator Wessels, H. T.
Hofland, L. J.
Van Der Wal, R.
Van Gastel, L.
Van Koetsveld, P. M.
De Herder, W. W.
De Jong, F. H.
description OBJECTIVE Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn‐omas). Since many of the NFAs and Gn‐omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pituitary adenomas. PATIENTS and METHODS Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn‐omas (n = 5), prolactinomas (n = 6) or growth hormone (GH)‐producing adenomas (n = 10). Actual protein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigated correlations between concentrations of these growth factors and hormones in NFAs and Gn‐omas. RESULTS Gn‐omas were found to secrete significantly more activin A in their culture medium than PRL‐ and GH‐producing adenomas (P 
doi_str_mv 10.1046/j.1365-2265.2001.01194.x
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T. ; Hofland, L. J. ; Van Der Wal, R. ; Van Gastel, L. ; Van Koetsveld, P. M. ; De Herder, W. W. ; De Jong, F. H.</creator><creatorcontrib>Wessels, H. T. ; Hofland, L. J. ; Van Der Wal, R. ; Van Gastel, L. ; Van Koetsveld, P. M. ; De Herder, W. W. ; De Jong, F. H.</creatorcontrib><description>OBJECTIVE Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn‐omas). Since many of the NFAs and Gn‐omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pituitary adenomas. PATIENTS and METHODS Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn‐omas (n = 5), prolactinomas (n = 6) or growth hormone (GH)‐producing adenomas (n = 10). Actual protein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigated correlations between concentrations of these growth factors and hormones in NFAs and Gn‐omas. RESULTS Gn‐omas were found to secrete significantly more activin A in their culture medium than PRL‐ and GH‐producing adenomas (P &lt; 0·05). Inhibin A and inhibin B protein levels in culture media were very low. A positive correlation between levels of activin A and FSH (r = 0·56, P &lt; 0·005) was found, while no correlation between activin A and LH could be detected. Furthermore, levels of follistatin were positively correlated with activin A levels (r = 0·73, P &lt; 0·0005). Comparison of the activin A:follistatin ratio with the measured FSH protein levels showed an even stronger relationship (r = 0·79, P &lt; 0·0005). CONCLUSIONS It is concluded that levels of activin A, follistatin and FSH in media of cultured nonfunctioning adenomas and gonadotroph adenomas are positively correlated. This suggests that these adenomas secrete FSH in response to the relatively high locally produced levels of activin A.</description><identifier>ISSN: 0300-0664</identifier><identifier>EISSN: 1365-2265</identifier><identifier>DOI: 10.1046/j.1365-2265.2001.01194.x</identifier><identifier>PMID: 11318784</identifier><identifier>CODEN: CLECAP</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Activins - analysis ; Activins - metabolism ; Adenoma - metabolism ; Adult ; Aged ; Analysis of Variance ; Biological and medical sciences ; Culture Media - chemistry ; Endocrinopathies ; Female ; Follicle Stimulating Hormone - analysis ; Follicle Stimulating Hormone - metabolism ; Follistatin ; Humans ; Hypothalamus. Hypophysis. Epiphysis (diseases) ; Inhibin-beta Subunits - analysis ; Inhibin-beta Subunits - metabolism ; Inhibins - analysis ; Luteinizing Hormone - analysis ; Male ; Medical sciences ; Middle Aged ; Non tumoral diseases. Target tissue resistance. Benign neoplasms ; Pituitary Neoplasms - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Cells, Cultured</subject><ispartof>Clinical endocrinology (Oxford), 2001-04, Vol.54 (4), p.485-492</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. 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T.</creatorcontrib><creatorcontrib>Hofland, L. J.</creatorcontrib><creatorcontrib>Van Der Wal, R.</creatorcontrib><creatorcontrib>Van Gastel, L.</creatorcontrib><creatorcontrib>Van Koetsveld, P. M.</creatorcontrib><creatorcontrib>De Herder, W. W.</creatorcontrib><creatorcontrib>De Jong, F. H.</creatorcontrib><title>In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clin Endocrinol (Oxf)</addtitle><description>OBJECTIVE Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn‐omas). Since many of the NFAs and Gn‐omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pituitary adenomas. PATIENTS and METHODS Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn‐omas (n = 5), prolactinomas (n = 6) or growth hormone (GH)‐producing adenomas (n = 10). Actual protein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigated correlations between concentrations of these growth factors and hormones in NFAs and Gn‐omas. RESULTS Gn‐omas were found to secrete significantly more activin A in their culture medium than PRL‐ and GH‐producing adenomas (P &lt; 0·05). Inhibin A and inhibin B protein levels in culture media were very low. A positive correlation between levels of activin A and FSH (r = 0·56, P &lt; 0·005) was found, while no correlation between activin A and LH could be detected. Furthermore, levels of follistatin were positively correlated with activin A levels (r = 0·73, P &lt; 0·0005). Comparison of the activin A:follistatin ratio with the measured FSH protein levels showed an even stronger relationship (r = 0·79, P &lt; 0·0005). CONCLUSIONS It is concluded that levels of activin A, follistatin and FSH in media of cultured nonfunctioning adenomas and gonadotroph adenomas are positively correlated. This suggests that these adenomas secrete FSH in response to the relatively high locally produced levels of activin A.</description><subject>Activins - analysis</subject><subject>Activins - metabolism</subject><subject>Adenoma - metabolism</subject><subject>Adult</subject><subject>Aged</subject><subject>Analysis of Variance</subject><subject>Biological and medical sciences</subject><subject>Culture Media - chemistry</subject><subject>Endocrinopathies</subject><subject>Female</subject><subject>Follicle Stimulating Hormone - analysis</subject><subject>Follicle Stimulating Hormone - metabolism</subject><subject>Follistatin</subject><subject>Humans</subject><subject>Hypothalamus. Hypophysis. Epiphysis (diseases)</subject><subject>Inhibin-beta Subunits - analysis</subject><subject>Inhibin-beta Subunits - metabolism</subject><subject>Inhibins - analysis</subject><subject>Luteinizing Hormone - analysis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Non tumoral diseases. Target tissue resistance. Benign neoplasms</subject><subject>Pituitary Neoplasms - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tumor Cells, Cultured</subject><issn>0300-0664</issn><issn>1365-2265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1uEzEUhS0EoqHwCsgCid0M1_NjzyxYlKhNq1Zl0SKWlsf2tA6OHeyZNHkeXhRPEwWJFStb9nfOPboHIUwgJ1DRz8uclLTOioLWeQFAciCkrfLtCzQ7frxEMygBMqC0OkFvYlwCQN0Ae41OCClJw5pqhn5fObwxQ_A4ahn0YLzDvscXd5e422E52mEMWmFpjTNSWLvDzrt-dHIijXvAwin84J1QPpmsH_HaDKMZRNhhobTzKxGxiViZoOWQ1NKHoK0YkueTGR6x9XvXdfBqlOnV6o22ccog0oyNcfjsLXrVCxv1u8N5ir5fnN_PL7Obb4ur-dlNJmtoqozIVisoKFGyU4L1hCpBi6oDxZqiJ23ZQlnUtGugVbqRfU1kpZXQTABToLryFH3a-6Ywv0YdB74yUWprhdN-jJwBSyZ1kcAP_4BLPwaXsnHSNrQhLasS1OwhGXyMQfd8HcwqLYYT4FOLfMmnsvhUFp9a5M8t8m2Svj_4j91Kq7_CQ20J-HgAREz764Nw0sQj19KqLGiivuypJ2P17r_H8_n57XRL-myvN3HQ26NehJ-cspLV_Mftgi_ar9cLVt_x-_IPbrfKkw</recordid><startdate>200104</startdate><enddate>200104</enddate><creator>Wessels, H. T.</creator><creator>Hofland, L. J.</creator><creator>Van Der Wal, R.</creator><creator>Van Gastel, L.</creator><creator>Van Koetsveld, P. M.</creator><creator>De Herder, W. W.</creator><creator>De Jong, F. H.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7QP</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>200104</creationdate><title>In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A</title><author>Wessels, H. T. ; Hofland, L. J. ; Van Der Wal, R. ; Van Gastel, L. ; Van Koetsveld, P. M. ; De Herder, W. W. ; De Jong, F. 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Epiphysis (diseases)</topic><topic>Inhibin-beta Subunits - analysis</topic><topic>Inhibin-beta Subunits - metabolism</topic><topic>Inhibins - analysis</topic><topic>Luteinizing Hormone - analysis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Non tumoral diseases. Target tissue resistance. Benign neoplasms</topic><topic>Pituitary Neoplasms - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wessels, H. T.</creatorcontrib><creatorcontrib>Hofland, L. J.</creatorcontrib><creatorcontrib>Van Der Wal, R.</creatorcontrib><creatorcontrib>Van Gastel, L.</creatorcontrib><creatorcontrib>Van Koetsveld, P. M.</creatorcontrib><creatorcontrib>De Herder, W. W.</creatorcontrib><creatorcontrib>De Jong, F. H.</creatorcontrib><collection>Istex</collection><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>Calcium &amp; Calcified Tissue Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical endocrinology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wessels, H. T.</au><au>Hofland, L. J.</au><au>Van Der Wal, R.</au><au>Van Gastel, L.</au><au>Van Koetsveld, P. M.</au><au>De Herder, W. W.</au><au>De Jong, F. H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clin Endocrinol (Oxf)</addtitle><date>2001-04</date><risdate>2001</risdate><volume>54</volume><issue>4</issue><spage>485</spage><epage>492</epage><pages>485-492</pages><issn>0300-0664</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><abstract>OBJECTIVE Expression of mRNAs encoding activin and its antagonists inhibin and follistatin has been described in human pituitary adenomas, including clinically nonfunctioning adenomas (NFAs) and gonadotroph adenomas (Gn‐omas). Since many of the NFAs and Gn‐omas secrete FSH in vitro, we hypothesized that locally produced activin may stimulate secretion of FSH in these pituitary adenomas. PATIENTS and METHODS Pituitary adenoma tissue was obtained from 38 patients diagnosed preoperatively as having NFAs (n = 17), Gn‐omas (n = 5), prolactinomas (n = 6) or growth hormone (GH)‐producing adenomas (n = 10). Actual protein levels of activin, inhibin, follistatin, FSH and LH were measured in media of these 38 cultured pituitary adenomas. In addition, we investigated correlations between concentrations of these growth factors and hormones in NFAs and Gn‐omas. RESULTS Gn‐omas were found to secrete significantly more activin A in their culture medium than PRL‐ and GH‐producing adenomas (P &lt; 0·05). Inhibin A and inhibin B protein levels in culture media were very low. A positive correlation between levels of activin A and FSH (r = 0·56, P &lt; 0·005) was found, while no correlation between activin A and LH could be detected. Furthermore, levels of follistatin were positively correlated with activin A levels (r = 0·73, P &lt; 0·0005). Comparison of the activin A:follistatin ratio with the measured FSH protein levels showed an even stronger relationship (r = 0·79, P &lt; 0·0005). CONCLUSIONS It is concluded that levels of activin A, follistatin and FSH in media of cultured nonfunctioning adenomas and gonadotroph adenomas are positively correlated. This suggests that these adenomas secrete FSH in response to the relatively high locally produced levels of activin A.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>11318784</pmid><doi>10.1046/j.1365-2265.2001.01194.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Activins - analysis
Activins - metabolism
Adenoma - metabolism
Adult
Aged
Analysis of Variance
Biological and medical sciences
Culture Media - chemistry
Endocrinopathies
Female
Follicle Stimulating Hormone - analysis
Follicle Stimulating Hormone - metabolism
Follistatin
Humans
Hypothalamus. Hypophysis. Epiphysis (diseases)
Inhibin-beta Subunits - analysis
Inhibin-beta Subunits - metabolism
Inhibins - analysis
Luteinizing Hormone - analysis
Male
Medical sciences
Middle Aged
Non tumoral diseases. Target tissue resistance. Benign neoplasms
Pituitary Neoplasms - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
title In vitro secretion of FSH by cultured clinically nonfunctioning and gonadotroph pituitary adenomas is directly correlated with locally produced levels of activin A
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