The Low Gonadotropin-Independent Constitutive Production of Testicular Testosterone Is Sufficient to Maintain Spermatogenesis
Spermatogenesis is thought to critically depend on the high intratesticular testosterone (T) levels induced by gonadotropic hormones. Strategies for hormonal male contraception are based on disruption of this regulatory mechanism through blockage of gonadotropin secretion. Although exogenous T or T...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2003-11, Vol.100 (23), p.13692-13697 |
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| creator | Zhang, Fu-Ping Pakarainen, Tomi Poutanen, Matti Toppari, Jorma Huhtaniemi, Ilpo |
| description | Spermatogenesis is thought to critically depend on the high intratesticular testosterone (T) levels induced by gonadotropic hormones. Strategies for hormonal male contraception are based on disruption of this regulatory mechanism through blockage of gonadotropin secretion. Although exogenous T or T plus progestin treatments efficiently block gonadotropin secretion and suppress testicular T production, only ≈60% of treated Caucasian men reach contraceptive azoospermia. We now report that in luteinizing hormone receptor knockout mice, qualitatively full spermatogenesis, up to elongated spermatids of late stages 13-16, is achieved at the age of 12 months, despite absent luteinizing hormone action and very low intratesticular T (2% of control level). However, postmeiotic spermiogenesis was blocked by the antiandrogen flutamide, indicating a crucial role of the residual low testicular T level in this process. The persistent follicle-stimulating hormone action in luteinizing hormone receptor knockout mice apparently stimulates spermatogenesis up to postmeiotic round spermatids, as observed in gonadotropin-deficient rodent models on follicle-stimulating hormone supplementation. The finding that spermatogenesis is possible without a luteinizing hormone-stimulated high level of intratesticular T contradicts the current dogma. Extrapolated to humans, it may indicate that only total abolition of testicular androgen action will result in consistent azoospermia, which is necessary for effective male contraception. |
| doi_str_mv | 10.1073/pnas.2232815100 |
| format | Article |
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Strategies for hormonal male contraception are based on disruption of this regulatory mechanism through blockage of gonadotropin secretion. Although exogenous T or T plus progestin treatments efficiently block gonadotropin secretion and suppress testicular T production, only ≈60% of treated Caucasian men reach contraceptive azoospermia. We now report that in luteinizing hormone receptor knockout mice, qualitatively full spermatogenesis, up to elongated spermatids of late stages 13-16, is achieved at the age of 12 months, despite absent luteinizing hormone action and very low intratesticular T (2% of control level). However, postmeiotic spermiogenesis was blocked by the antiandrogen flutamide, indicating a crucial role of the residual low testicular T level in this process. The persistent follicle-stimulating hormone action in luteinizing hormone receptor knockout mice apparently stimulates spermatogenesis up to postmeiotic round spermatids, as observed in gonadotropin-deficient rodent models on follicle-stimulating hormone supplementation. The finding that spermatogenesis is possible without a luteinizing hormone-stimulated high level of intratesticular T contradicts the current dogma. Extrapolated to humans, it may indicate that only total abolition of testicular androgen action will result in consistent azoospermia, which is necessary for effective male contraception.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2232815100</identifier><identifier>PMID: 14585929</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>17-Hydroxysteroid Dehydrogenases - metabolism ; Anatomy & physiology ; Androgens ; Androgens - metabolism ; Animals ; Biological Sciences ; Birth control ; Colforsin - metabolism ; Flutamide - pharmacology ; Gonadotropins ; Gonadotropins - metabolism ; Histology ; Homozygote ; Hormones ; Humans ; Immunohistochemistry ; Leydig cells ; Male ; Meiosis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Protamines ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Sex hormones ; Signal Transduction ; Spermatids ; Spermatogenesis ; Testes ; Testis - pathology ; Testosterone - biosynthesis ; Testosterone - metabolism ; Thrombospondins - metabolism ; Time Factors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2003-11, Vol.100 (23), p.13692-13697</ispartof><rights>Copyright 1993-2003 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 11, 2003</rights><rights>Copyright © 2003, The National Academy of Sciences 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c561t-4546375061d55c03207e6f66f04d1039b1e58f3e7ccca574124cd6adcbd36ee13</citedby><cites>FETCH-LOGICAL-c561t-4546375061d55c03207e6f66f04d1039b1e58f3e7ccca574124cd6adcbd36ee13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/100/23.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3148201$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3148201$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14585929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Fu-Ping</creatorcontrib><creatorcontrib>Pakarainen, Tomi</creatorcontrib><creatorcontrib>Poutanen, Matti</creatorcontrib><creatorcontrib>Toppari, Jorma</creatorcontrib><creatorcontrib>Huhtaniemi, Ilpo</creatorcontrib><title>The Low Gonadotropin-Independent Constitutive Production of Testicular Testosterone Is Sufficient to Maintain Spermatogenesis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Spermatogenesis is thought to critically depend on the high intratesticular testosterone (T) levels induced by gonadotropic hormones. Strategies for hormonal male contraception are based on disruption of this regulatory mechanism through blockage of gonadotropin secretion. Although exogenous T or T plus progestin treatments efficiently block gonadotropin secretion and suppress testicular T production, only ≈60% of treated Caucasian men reach contraceptive azoospermia. We now report that in luteinizing hormone receptor knockout mice, qualitatively full spermatogenesis, up to elongated spermatids of late stages 13-16, is achieved at the age of 12 months, despite absent luteinizing hormone action and very low intratesticular T (2% of control level). However, postmeiotic spermiogenesis was blocked by the antiandrogen flutamide, indicating a crucial role of the residual low testicular T level in this process. The persistent follicle-stimulating hormone action in luteinizing hormone receptor knockout mice apparently stimulates spermatogenesis up to postmeiotic round spermatids, as observed in gonadotropin-deficient rodent models on follicle-stimulating hormone supplementation. The finding that spermatogenesis is possible without a luteinizing hormone-stimulated high level of intratesticular T contradicts the current dogma. Extrapolated to humans, it may indicate that only total abolition of testicular androgen action will result in consistent azoospermia, which is necessary for effective male contraception.</description><subject>17-Hydroxysteroid Dehydrogenases - metabolism</subject><subject>Anatomy & physiology</subject><subject>Androgens</subject><subject>Androgens - metabolism</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Birth control</subject><subject>Colforsin - metabolism</subject><subject>Flutamide - pharmacology</subject><subject>Gonadotropins</subject><subject>Gonadotropins - metabolism</subject><subject>Histology</subject><subject>Homozygote</subject><subject>Hormones</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Leydig cells</subject><subject>Male</subject><subject>Meiosis</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Phenotype</subject><subject>Protamines</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Sex hormones</subject><subject>Signal Transduction</subject><subject>Spermatids</subject><subject>Spermatogenesis</subject><subject>Testes</subject><subject>Testis - pathology</subject><subject>Testosterone - biosynthesis</subject><subject>Testosterone - metabolism</subject><subject>Thrombospondins - metabolism</subject><subject>Time Factors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtvEzEUhS0EoqGwZoOQxQKJxbR-z8yiCxSVEikIpIa15XjutI4m9mB7Cl3w33FI1AAbFn5I9ztX5-gg9JKSM0pqfj56k84Y46yhkhLyCM0oaWmlREseoxkhrK4awcQJepbShhDSyoY8RSdUyEa2rJ2hn6tbwMvwHV8Fb7qQYxidrxa-gxHK5TOeB5-yy1N2d4C_xNBNNrvgcejxCsrEToOJv78hZYjBA14kfD31vbNutyAH_Mk4n8vB1yPErcnhBjwkl56jJ70ZErw4vKfo64fL1fxjtfx8tZi_X1ZWKporIYXitSSKdlJawhmpQfVK9UR0lPB2TUE2PYfaWmtkLSgTtlOms-uOKwDKT9HFfu84rbfQ2WIrmkGP0W1NvNfBOP33xLtbfRPuNFO8qWXRvz3oY_g2lah665KFYTAewpR0TbloGl4X8M0_4CZM0ZdsmhEqSgGsKdD5HrIxpBShfzBCid7Vqne16mOtRfH6T_9H_tBjAd4dgJ3yuI5oxjXlqmW6n4Yhw49cWPwftiCv9simtBofGE5FU2LwX1g5w6c</recordid><startdate>20031111</startdate><enddate>20031111</enddate><creator>Zhang, Fu-Ping</creator><creator>Pakarainen, Tomi</creator><creator>Poutanen, Matti</creator><creator>Toppari, Jorma</creator><creator>Huhtaniemi, Ilpo</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20031111</creationdate><title>The Low Gonadotropin-Independent Constitutive Production of Testicular Testosterone Is Sufficient to Maintain Spermatogenesis</title><author>Zhang, Fu-Ping ; 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Strategies for hormonal male contraception are based on disruption of this regulatory mechanism through blockage of gonadotropin secretion. Although exogenous T or T plus progestin treatments efficiently block gonadotropin secretion and suppress testicular T production, only ≈60% of treated Caucasian men reach contraceptive azoospermia. We now report that in luteinizing hormone receptor knockout mice, qualitatively full spermatogenesis, up to elongated spermatids of late stages 13-16, is achieved at the age of 12 months, despite absent luteinizing hormone action and very low intratesticular T (2% of control level). However, postmeiotic spermiogenesis was blocked by the antiandrogen flutamide, indicating a crucial role of the residual low testicular T level in this process. The persistent follicle-stimulating hormone action in luteinizing hormone receptor knockout mice apparently stimulates spermatogenesis up to postmeiotic round spermatids, as observed in gonadotropin-deficient rodent models on follicle-stimulating hormone supplementation. The finding that spermatogenesis is possible without a luteinizing hormone-stimulated high level of intratesticular T contradicts the current dogma. Extrapolated to humans, it may indicate that only total abolition of testicular androgen action will result in consistent azoospermia, which is necessary for effective male contraception.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>14585929</pmid><doi>10.1073/pnas.2232815100</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 17-Hydroxysteroid Dehydrogenases - metabolism Anatomy & physiology Androgens Androgens - metabolism Animals Biological Sciences Birth control Colforsin - metabolism Flutamide - pharmacology Gonadotropins Gonadotropins - metabolism Histology Homozygote Hormones Humans Immunohistochemistry Leydig cells Male Meiosis Mice Mice, Inbred C57BL Mice, Knockout Phenotype Protamines Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Sex hormones Signal Transduction Spermatids Spermatogenesis Testes Testis - pathology Testosterone - biosynthesis Testosterone - metabolism Thrombospondins - metabolism Time Factors |
| title | The Low Gonadotropin-Independent Constitutive Production of Testicular Testosterone Is Sufficient to Maintain Spermatogenesis |
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