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Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell‐only syndrome
Summary Several observational studies have showed a combination of lower testosterone (T) to LH ratio and higher estradiol (E2) to T ratio in secretory infertile men compared to men with normal spermatogenesis, suggesting a steroidogenic dysfunction of Leydig cells (Lc) that may involve increased ar...
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| Published in: | Andrology (Oxford) 2017-01, Vol.5 (1), p.41-48 |
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| container_title | Andrology (Oxford) |
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| creator | Lardone, M. C. Argandoña, F. Flórez, M. Parada‐Bustamante, A. Ebensperger, M. Palma, C. Piottante, A. Castro, A. |
| description | Summary
Several observational studies have showed a combination of lower testosterone (T) to LH ratio and higher estradiol (E2) to T ratio in secretory infertile men compared to men with normal spermatogenesis, suggesting a steroidogenic dysfunction of Leydig cells (Lc) that may involve increased aromatase activity. Low T/LH ratio is associated with Lc hyperplasia, which together with LH hyperstimulation may represent compensation for impaired T production. Aromatase expression and oestrogen production are mainly detected in Lc of the testis, although Sertoli and germ cells also contribute to testicular aromatase activity. The aim of this study was to assess the transcriptional expression of CYP19A1 (aromatase) in isolated Lc of subjects with Sertoli cell‐only syndrome (SCOS) and signs of Lc impairment. Nineteen patients with SCOS and 10 controls with normal spermatogenesis who had medical indication of testicular biopsy for sperm retrieval were studied. Leydig cells were isolated by Laser Capture Microdissection (LCM) and CYP19A1 mRNA expression was quantified by SYBR® Green‐based qPCR. In addition, testicular T and E2 and serum hormonal levels were measured. Relative to control group, CYP19A1 was overexpressed more than twofold in 10/19 cases (2.3–12.2‐fold increase), showing a significant increment in cases with low T/LH ratio (T/LH |
| doi_str_mv | 10.1111/andr.12289 |
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Several observational studies have showed a combination of lower testosterone (T) to LH ratio and higher estradiol (E2) to T ratio in secretory infertile men compared to men with normal spermatogenesis, suggesting a steroidogenic dysfunction of Leydig cells (Lc) that may involve increased aromatase activity. Low T/LH ratio is associated with Lc hyperplasia, which together with LH hyperstimulation may represent compensation for impaired T production. Aromatase expression and oestrogen production are mainly detected in Lc of the testis, although Sertoli and germ cells also contribute to testicular aromatase activity. The aim of this study was to assess the transcriptional expression of CYP19A1 (aromatase) in isolated Lc of subjects with Sertoli cell‐only syndrome (SCOS) and signs of Lc impairment. Nineteen patients with SCOS and 10 controls with normal spermatogenesis who had medical indication of testicular biopsy for sperm retrieval were studied. Leydig cells were isolated by Laser Capture Microdissection (LCM) and CYP19A1 mRNA expression was quantified by SYBR® Green‐based qPCR. In addition, testicular T and E2 and serum hormonal levels were measured. Relative to control group, CYP19A1 was overexpressed more than twofold in 10/19 cases (2.3–12.2‐fold increase), showing a significant increment in cases with low T/LH ratio (T/LH < 2) compared to cases with T/LH ≥ 2 (p = 0.038, REST®). Moreover, Rq data for CYP19A1 had a direct correlation with testicular levels of E2 and the E2/T ratio (r = 0.869; p < 0.001 and r = 0.633; p = 0.005). In summary, Lc from infertile patients with signs of Lc dysfunction overexpressed aromatase and showed an increment of testicular E2. Our results suggest that increased expression of aromatase in Lc leads to higher E2 production and may account for the functional impairment of the Lc in patients with SCOS.</description><identifier>ISSN: 2047-2919</identifier><identifier>EISSN: 2047-2927</identifier><identifier>DOI: 10.1111/andr.12289</identifier><identifier>PMID: 27769104</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adult ; Androgens ; aromatase ; Aromatase - genetics ; Aromatase - metabolism ; Estradiol - blood ; Estrogens ; Follicle Stimulating Hormone - blood ; Humans ; Laser Capture Microdissection ; Leydig cell dysfunction ; Leydig Cells - metabolism ; Luteinizing Hormone - blood ; Male ; Sertoli Cell-Only Syndrome - genetics ; Sertoli Cell-Only Syndrome - metabolism ; Spermatogenesis ; Spermatogenesis - genetics ; spermatogenic failure ; Testis - metabolism ; Testosterone - blood</subject><ispartof>Andrology (Oxford), 2017-01, Vol.5 (1), p.41-48</ispartof><rights>2016 American Society of Andrology and European Academy of Andrology</rights><rights>2016 American Society of Andrology and European Academy of Andrology.</rights><rights>Andrology © 2017 American Society of Andrology and European Academy of Andrology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27769104$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lardone, M. C.</creatorcontrib><creatorcontrib>Argandoña, F.</creatorcontrib><creatorcontrib>Flórez, M.</creatorcontrib><creatorcontrib>Parada‐Bustamante, A.</creatorcontrib><creatorcontrib>Ebensperger, M.</creatorcontrib><creatorcontrib>Palma, C.</creatorcontrib><creatorcontrib>Piottante, A.</creatorcontrib><creatorcontrib>Castro, A.</creatorcontrib><title>Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell‐only syndrome</title><title>Andrology (Oxford)</title><addtitle>Andrology</addtitle><description>Summary
Several observational studies have showed a combination of lower testosterone (T) to LH ratio and higher estradiol (E2) to T ratio in secretory infertile men compared to men with normal spermatogenesis, suggesting a steroidogenic dysfunction of Leydig cells (Lc) that may involve increased aromatase activity. Low T/LH ratio is associated with Lc hyperplasia, which together with LH hyperstimulation may represent compensation for impaired T production. Aromatase expression and oestrogen production are mainly detected in Lc of the testis, although Sertoli and germ cells also contribute to testicular aromatase activity. The aim of this study was to assess the transcriptional expression of CYP19A1 (aromatase) in isolated Lc of subjects with Sertoli cell‐only syndrome (SCOS) and signs of Lc impairment. Nineteen patients with SCOS and 10 controls with normal spermatogenesis who had medical indication of testicular biopsy for sperm retrieval were studied. Leydig cells were isolated by Laser Capture Microdissection (LCM) and CYP19A1 mRNA expression was quantified by SYBR® Green‐based qPCR. In addition, testicular T and E2 and serum hormonal levels were measured. Relative to control group, CYP19A1 was overexpressed more than twofold in 10/19 cases (2.3–12.2‐fold increase), showing a significant increment in cases with low T/LH ratio (T/LH < 2) compared to cases with T/LH ≥ 2 (p = 0.038, REST®). Moreover, Rq data for CYP19A1 had a direct correlation with testicular levels of E2 and the E2/T ratio (r = 0.869; p < 0.001 and r = 0.633; p = 0.005). In summary, Lc from infertile patients with signs of Lc dysfunction overexpressed aromatase and showed an increment of testicular E2. Our results suggest that increased expression of aromatase in Lc leads to higher E2 production and may account for the functional impairment of the Lc in patients with SCOS.</description><subject>Adult</subject><subject>Androgens</subject><subject>aromatase</subject><subject>Aromatase - genetics</subject><subject>Aromatase - metabolism</subject><subject>Estradiol - blood</subject><subject>Estrogens</subject><subject>Follicle Stimulating Hormone - blood</subject><subject>Humans</subject><subject>Laser Capture Microdissection</subject><subject>Leydig cell dysfunction</subject><subject>Leydig Cells - metabolism</subject><subject>Luteinizing Hormone - blood</subject><subject>Male</subject><subject>Sertoli Cell-Only Syndrome - genetics</subject><subject>Sertoli Cell-Only Syndrome - metabolism</subject><subject>Spermatogenesis</subject><subject>Spermatogenesis - genetics</subject><subject>spermatogenic failure</subject><subject>Testis - metabolism</subject><subject>Testosterone - blood</subject><issn>2047-2919</issn><issn>2047-2927</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpdkc9O3DAQxq2qqCDgwgNUlrj0stRje5P4uFpKi7QqVf8cOEVOPKFeJfHiSQq59QkqnpEnIdkFDh1Z8kj--dM38zF2AuIMxvpoWxfPQMrMvGEHUuh0Jo1M3772YPbZMdFajJVNR75j-zJNEwNCH7B_V38w4v0mIpEPLQ8VX15_A7MAbmNobGcJuW_5Cgfnb3iJdU3cE7dEofS2Q8fvfPebU4cxeBdusPUldwNVfVt2k-L4mfpijWVHO_QHxi7Ufqv1-PchtPXAaRjHCA0esb3K1oTHz_ch-3Xx6efyy2x19flyuVjNNgpSMzPSCmWcMImCDKsMMJOlMoVOEgHVPIF5oa3VxkmQaJUV6GxhtVNolEoyUIfsw053E8Ntj9TljafJkG0x9JRDpuZz0FqqET39D12HPraju5HSJgMjk4l6_0z1RYMu30Tf2DjkL5seAdgBd77G4fUdRD7FmE8x5tsY88XX8-_bTj0B1O6RrQ</recordid><startdate>201701</startdate><enddate>201701</enddate><creator>Lardone, M. C.</creator><creator>Argandoña, F.</creator><creator>Flórez, M.</creator><creator>Parada‐Bustamante, A.</creator><creator>Ebensperger, M.</creator><creator>Palma, C.</creator><creator>Piottante, A.</creator><creator>Castro, A.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201701</creationdate><title>Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell‐only syndrome</title><author>Lardone, M. C. ; Argandoña, F. ; Flórez, M. ; Parada‐Bustamante, A. ; Ebensperger, M. ; Palma, C. ; Piottante, A. ; Castro, A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3179-92a039d096318ef81e82c39b46601f5615b4aa49d212ea3a0edaba4d3e9336813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Androgens</topic><topic>aromatase</topic><topic>Aromatase - genetics</topic><topic>Aromatase - metabolism</topic><topic>Estradiol - blood</topic><topic>Estrogens</topic><topic>Follicle Stimulating Hormone - blood</topic><topic>Humans</topic><topic>Laser Capture Microdissection</topic><topic>Leydig cell dysfunction</topic><topic>Leydig Cells - metabolism</topic><topic>Luteinizing Hormone - blood</topic><topic>Male</topic><topic>Sertoli Cell-Only Syndrome - genetics</topic><topic>Sertoli Cell-Only Syndrome - metabolism</topic><topic>Spermatogenesis</topic><topic>Spermatogenesis - genetics</topic><topic>spermatogenic failure</topic><topic>Testis - metabolism</topic><topic>Testosterone - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lardone, M. C.</creatorcontrib><creatorcontrib>Argandoña, F.</creatorcontrib><creatorcontrib>Flórez, M.</creatorcontrib><creatorcontrib>Parada‐Bustamante, A.</creatorcontrib><creatorcontrib>Ebensperger, M.</creatorcontrib><creatorcontrib>Palma, C.</creatorcontrib><creatorcontrib>Piottante, A.</creatorcontrib><creatorcontrib>Castro, A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Andrology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lardone, M. C.</au><au>Argandoña, F.</au><au>Flórez, M.</au><au>Parada‐Bustamante, A.</au><au>Ebensperger, M.</au><au>Palma, C.</au><au>Piottante, A.</au><au>Castro, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell‐only syndrome</atitle><jtitle>Andrology (Oxford)</jtitle><addtitle>Andrology</addtitle><date>2017-01</date><risdate>2017</risdate><volume>5</volume><issue>1</issue><spage>41</spage><epage>48</epage><pages>41-48</pages><issn>2047-2919</issn><eissn>2047-2927</eissn><abstract>Summary
Several observational studies have showed a combination of lower testosterone (T) to LH ratio and higher estradiol (E2) to T ratio in secretory infertile men compared to men with normal spermatogenesis, suggesting a steroidogenic dysfunction of Leydig cells (Lc) that may involve increased aromatase activity. Low T/LH ratio is associated with Lc hyperplasia, which together with LH hyperstimulation may represent compensation for impaired T production. Aromatase expression and oestrogen production are mainly detected in Lc of the testis, although Sertoli and germ cells also contribute to testicular aromatase activity. The aim of this study was to assess the transcriptional expression of CYP19A1 (aromatase) in isolated Lc of subjects with Sertoli cell‐only syndrome (SCOS) and signs of Lc impairment. Nineteen patients with SCOS and 10 controls with normal spermatogenesis who had medical indication of testicular biopsy for sperm retrieval were studied. Leydig cells were isolated by Laser Capture Microdissection (LCM) and CYP19A1 mRNA expression was quantified by SYBR® Green‐based qPCR. In addition, testicular T and E2 and serum hormonal levels were measured. Relative to control group, CYP19A1 was overexpressed more than twofold in 10/19 cases (2.3–12.2‐fold increase), showing a significant increment in cases with low T/LH ratio (T/LH < 2) compared to cases with T/LH ≥ 2 (p = 0.038, REST®). Moreover, Rq data for CYP19A1 had a direct correlation with testicular levels of E2 and the E2/T ratio (r = 0.869; p < 0.001 and r = 0.633; p = 0.005). In summary, Lc from infertile patients with signs of Lc dysfunction overexpressed aromatase and showed an increment of testicular E2. Our results suggest that increased expression of aromatase in Lc leads to higher E2 production and may account for the functional impairment of the Lc in patients with SCOS.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>27769104</pmid><doi>10.1111/andr.12289</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Andrology (Oxford), 2017-01, Vol.5 (1), p.41-48 |
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| subjects | Adult Androgens aromatase Aromatase - genetics Aromatase - metabolism Estradiol - blood Estrogens Follicle Stimulating Hormone - blood Humans Laser Capture Microdissection Leydig cell dysfunction Leydig Cells - metabolism Luteinizing Hormone - blood Male Sertoli Cell-Only Syndrome - genetics Sertoli Cell-Only Syndrome - metabolism Spermatogenesis Spermatogenesis - genetics spermatogenic failure Testis - metabolism Testosterone - blood |
| title | Overexpression of CYP19A1 aromatase in Leydig cells is associated with steroidogenic dysfunction in subjects with Sertoli cell‐only syndrome |
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