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Suppression and recovery of LH secretion by a potent and selective GnRH-receptor antagonist peptide in healthy early follicular-phase women are mediated via selective control of LH secretory burst mass
Summary aim GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH‐secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of t...
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| Published in: | Clinical endocrinology (Oxford) 2003-10, Vol.59 (4), p.526-532 |
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| container_title | Clinical endocrinology (Oxford) |
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| creator | Gianotti, L. Veldhuis, J. D. Destefanis, S. Lanfranco, F. Ramunni, J. Arvat, E. Marzetto, M. Boutignon, F. Deghenghi, R. Ghigo, E. |
| description | Summary
aim GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH‐secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of this study was to evaluate the effects of a potent GnRH antagonist, Teverelix (TEV), on the gonadal axis in healthy young women.
subjects and measurements In nine women [20–35 years old, body mass index (BMI) 19–25 kg/m2] in the early follicular phase, serum LH and FSH levels were evaluated every 10 min from 08·00 to 12·00 h before, and 24 h and 96 h after TEV injection (2·5 mg in 1 ml subcutaneusly on day 0). Serum gonadotrophin and oestradiol levels were also evaluated at baseline and at 6, 8, 12, 48, 72 h after TEV.
results The antagonist reduced both serum LH and FSH concentrations; LH levels were significantly and promptly reduced at +6 h (nadir at +8 h) until +48 h and recovered at +72 h, while FSH levels were reduced (P |
| doi_str_mv | 10.1046/j.1365-2265.2003.01882.x |
| format | article |
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aim GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH‐secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of this study was to evaluate the effects of a potent GnRH antagonist, Teverelix (TEV), on the gonadal axis in healthy young women.
subjects and measurements In nine women [20–35 years old, body mass index (BMI) 19–25 kg/m2] in the early follicular phase, serum LH and FSH levels were evaluated every 10 min from 08·00 to 12·00 h before, and 24 h and 96 h after TEV injection (2·5 mg in 1 ml subcutaneusly on day 0). Serum gonadotrophin and oestradiol levels were also evaluated at baseline and at 6, 8, 12, 48, 72 h after TEV.
results The antagonist reduced both serum LH and FSH concentrations; LH levels were significantly and promptly reduced at +6 h (nadir at +8 h) until +48 h and recovered at +72 h, while FSH levels were reduced (P < 0·05) 24 h after the antagonist and normalized at +48 h. LH (but not FSH) concentrations at +96 h exceeded baseline (P < 0·05). TEV suppressed oestradiol concentrations (P < 0·05) with a nadir at +24 h, comparable reduction at +48 h and recovery to baseline at +72 h. Deconvolution analysis showed that the antagonist peptide suppressed (P < 0·02) the pulsatile production rate, burst mass and amplitude of LH on day 1. Pulsatile FSH secretion also fell at this time (P < 0·05). LH and FSH pulse frequency were not modified by TEV. At +96 h, LH pulsatility did not significantly differ from that at baseline. Suppression of mean LH or FSH concentrations did not affect the relative pattern regularity (approximate entropy) of LH and FSH secretion.
conclusions This study demonstrates that the acute administration of a potent GnRH antagonist induces prompt inhibition of the gonadal axis lasting for 2 days in women due to mechanistically specific suppression of LH secretory burst mass and the mean FSH secretion rate. The trend toward rebound release of LH following the end of the pharmacological effect of the antagonist could reflect a rise in endogenous GnRH activity.</description><identifier>ISSN: 0300-0664</identifier><identifier>EISSN: 1365-2265</identifier><identifier>DOI: 10.1046/j.1365-2265.2003.01882.x</identifier><identifier>PMID: 14510918</identifier><identifier>CODEN: CLECAP</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; Biological and medical sciences ; Endocrinopathies ; Estradiol - blood ; Female ; Follicle Stimulating Hormone - blood ; Follicle Stimulating Hormone - metabolism ; Follicular Phase - physiology ; Fundamental and applied biological sciences. Psychology ; Hormone Antagonists - pharmacology ; Humans ; Injections, Subcutaneous ; Luteinizing Hormone - blood ; Luteinizing Hormone - metabolism ; Medical sciences ; Oligopeptides - pharmacology ; Ovary - drug effects ; Radioimmunoassay - methods ; Receptors, LHRH - antagonists & inhibitors ; Secretory Rate - drug effects ; Time Factors ; Vertebrates: endocrinology</subject><ispartof>Clinical endocrinology (Oxford), 2003-10, Vol.59 (4), p.526-532</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. Oct 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4602-f682d41a8f86d06f56ec43673571f804631429273e3adf54af4c8a73cdd8fd33</citedby><cites>FETCH-LOGICAL-c4602-f682d41a8f86d06f56ec43673571f804631429273e3adf54af4c8a73cdd8fd33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15149796$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14510918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gianotti, L.</creatorcontrib><creatorcontrib>Veldhuis, J. D.</creatorcontrib><creatorcontrib>Destefanis, S.</creatorcontrib><creatorcontrib>Lanfranco, F.</creatorcontrib><creatorcontrib>Ramunni, J.</creatorcontrib><creatorcontrib>Arvat, E.</creatorcontrib><creatorcontrib>Marzetto, M.</creatorcontrib><creatorcontrib>Boutignon, F.</creatorcontrib><creatorcontrib>Deghenghi, R.</creatorcontrib><creatorcontrib>Ghigo, E.</creatorcontrib><title>Suppression and recovery of LH secretion by a potent and selective GnRH-receptor antagonist peptide in healthy early follicular-phase women are mediated via selective control of LH secretory burst mass</title><title>Clinical endocrinology (Oxford)</title><addtitle>Clin Endocrinol (Oxf)</addtitle><description>Summary
aim GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH‐secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of this study was to evaluate the effects of a potent GnRH antagonist, Teverelix (TEV), on the gonadal axis in healthy young women.
subjects and measurements In nine women [20–35 years old, body mass index (BMI) 19–25 kg/m2] in the early follicular phase, serum LH and FSH levels were evaluated every 10 min from 08·00 to 12·00 h before, and 24 h and 96 h after TEV injection (2·5 mg in 1 ml subcutaneusly on day 0). Serum gonadotrophin and oestradiol levels were also evaluated at baseline and at 6, 8, 12, 48, 72 h after TEV.
results The antagonist reduced both serum LH and FSH concentrations; LH levels were significantly and promptly reduced at +6 h (nadir at +8 h) until +48 h and recovered at +72 h, while FSH levels were reduced (P < 0·05) 24 h after the antagonist and normalized at +48 h. LH (but not FSH) concentrations at +96 h exceeded baseline (P < 0·05). TEV suppressed oestradiol concentrations (P < 0·05) with a nadir at +24 h, comparable reduction at +48 h and recovery to baseline at +72 h. Deconvolution analysis showed that the antagonist peptide suppressed (P < 0·02) the pulsatile production rate, burst mass and amplitude of LH on day 1. Pulsatile FSH secretion also fell at this time (P < 0·05). LH and FSH pulse frequency were not modified by TEV. At +96 h, LH pulsatility did not significantly differ from that at baseline. Suppression of mean LH or FSH concentrations did not affect the relative pattern regularity (approximate entropy) of LH and FSH secretion.
conclusions This study demonstrates that the acute administration of a potent GnRH antagonist induces prompt inhibition of the gonadal axis lasting for 2 days in women due to mechanistically specific suppression of LH secretory burst mass and the mean FSH secretion rate. The trend toward rebound release of LH following the end of the pharmacological effect of the antagonist could reflect a rise in endogenous GnRH activity.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Endocrinopathies</subject><subject>Estradiol - blood</subject><subject>Female</subject><subject>Follicle Stimulating Hormone - blood</subject><subject>Follicle Stimulating Hormone - metabolism</subject><subject>Follicular Phase - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hormone Antagonists - pharmacology</subject><subject>Humans</subject><subject>Injections, Subcutaneous</subject><subject>Luteinizing Hormone - blood</subject><subject>Luteinizing Hormone - metabolism</subject><subject>Medical sciences</subject><subject>Oligopeptides - pharmacology</subject><subject>Ovary - drug effects</subject><subject>Radioimmunoassay - methods</subject><subject>Receptors, LHRH - antagonists & inhibitors</subject><subject>Secretory Rate - drug effects</subject><subject>Time Factors</subject><subject>Vertebrates: endocrinology</subject><issn>0300-0664</issn><issn>1365-2265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqNkc2O0zAUhSMEYsrAKyALCXYp_kviLFigamiRqkEaRmJpuc41dXHjYCed5hF5K5xpNQOsWNny_Y7v0TlZhgieE8zL97s5YWWRU1oWc4oxm2MiBJ0fn2Szh8HTbIYZxjkuS36RvYhxhzEuBK6eZxeEFwTXRMyyX1-HrgsQo_UtUm2DAmh_gDAib9B6hSLoAP003IxIoc730Pb3YAQHurcHQMv2ZpUnHXS9D2nWq---tbFHXXqxDSDboi0o129HBCq4ERnvnNWDUyHvtioCuvN7SPsDoD00VvXQoINVf-zQvu2Dd3-58snlZghp0V7F-DJ7ZpSL8Op8Xma3n65uF6t8_WX5efFxnWteYpqbUtCGEyWMKBtcmqIEzVlZsaIiRqRwGeG0phUDphpTcGW4FqpiummEaRi7zN6dvu2C_zlA7OXeRg3OqRb8EGVVVJin_BP45h9w54fQJmuS1EIQWjCRIHGCdPAxBjCyC3avwigJllPVcienRuXUqJyqlvdVy2OSvj7_P2xSaI_Cc7cJeHsGVNTKmaBabeMjVxBeV_Vk9MOJu7MOxv82IBdX19Mt6fOTPlUOxwe9Cj9kirUq5LfrpVxVK1rd1FxS9hufxNcV</recordid><startdate>200310</startdate><enddate>200310</enddate><creator>Gianotti, L.</creator><creator>Veldhuis, J. D.</creator><creator>Destefanis, S.</creator><creator>Lanfranco, F.</creator><creator>Ramunni, J.</creator><creator>Arvat, E.</creator><creator>Marzetto, M.</creator><creator>Boutignon, F.</creator><creator>Deghenghi, R.</creator><creator>Ghigo, E.</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>200310</creationdate><title>Suppression and recovery of LH secretion by a potent and selective GnRH-receptor antagonist peptide in healthy early follicular-phase women are mediated via selective control of LH secretory burst mass</title><author>Gianotti, L. ; Veldhuis, J. D. ; Destefanis, S. ; Lanfranco, F. ; Ramunni, J. ; Arvat, E. ; Marzetto, M. ; Boutignon, F. ; Deghenghi, R. ; Ghigo, E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4602-f682d41a8f86d06f56ec43673571f804631429273e3adf54af4c8a73cdd8fd33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Endocrinopathies</topic><topic>Estradiol - blood</topic><topic>Female</topic><topic>Follicle Stimulating Hormone - blood</topic><topic>Follicle Stimulating Hormone - metabolism</topic><topic>Follicular Phase - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Hormone Antagonists - pharmacology</topic><topic>Humans</topic><topic>Injections, Subcutaneous</topic><topic>Luteinizing Hormone - blood</topic><topic>Luteinizing Hormone - metabolism</topic><topic>Medical sciences</topic><topic>Oligopeptides - pharmacology</topic><topic>Ovary - drug effects</topic><topic>Radioimmunoassay - methods</topic><topic>Receptors, LHRH - antagonists & inhibitors</topic><topic>Secretory Rate - drug effects</topic><topic>Time Factors</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gianotti, L.</creatorcontrib><creatorcontrib>Veldhuis, J. D.</creatorcontrib><creatorcontrib>Destefanis, S.</creatorcontrib><creatorcontrib>Lanfranco, F.</creatorcontrib><creatorcontrib>Ramunni, J.</creatorcontrib><creatorcontrib>Arvat, E.</creatorcontrib><creatorcontrib>Marzetto, M.</creatorcontrib><creatorcontrib>Boutignon, F.</creatorcontrib><creatorcontrib>Deghenghi, R.</creatorcontrib><creatorcontrib>Ghigo, E.</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 & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & 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>Gianotti, L.</au><au>Veldhuis, J. D.</au><au>Destefanis, S.</au><au>Lanfranco, F.</au><au>Ramunni, J.</au><au>Arvat, E.</au><au>Marzetto, M.</au><au>Boutignon, F.</au><au>Deghenghi, R.</au><au>Ghigo, E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppression and recovery of LH secretion by a potent and selective GnRH-receptor antagonist peptide in healthy early follicular-phase women are mediated via selective control of LH secretory burst mass</atitle><jtitle>Clinical endocrinology (Oxford)</jtitle><addtitle>Clin Endocrinol (Oxf)</addtitle><date>2003-10</date><risdate>2003</risdate><volume>59</volume><issue>4</issue><spage>526</spage><epage>532</epage><pages>526-532</pages><issn>0300-0664</issn><eissn>1365-2265</eissn><coden>CLECAP</coden><abstract>Summary
aim GnRH antagonists are competitive inhibitors of GnRH receptors. Their administration induces prompt suppression of the gonadal axis. In animals, GnRH antagonists upregulate the activity of GnRH‐secreting neurones, which could cause gonadotrophin rebound following inhibition. The aim of this study was to evaluate the effects of a potent GnRH antagonist, Teverelix (TEV), on the gonadal axis in healthy young women.
subjects and measurements In nine women [20–35 years old, body mass index (BMI) 19–25 kg/m2] in the early follicular phase, serum LH and FSH levels were evaluated every 10 min from 08·00 to 12·00 h before, and 24 h and 96 h after TEV injection (2·5 mg in 1 ml subcutaneusly on day 0). Serum gonadotrophin and oestradiol levels were also evaluated at baseline and at 6, 8, 12, 48, 72 h after TEV.
results The antagonist reduced both serum LH and FSH concentrations; LH levels were significantly and promptly reduced at +6 h (nadir at +8 h) until +48 h and recovered at +72 h, while FSH levels were reduced (P < 0·05) 24 h after the antagonist and normalized at +48 h. LH (but not FSH) concentrations at +96 h exceeded baseline (P < 0·05). TEV suppressed oestradiol concentrations (P < 0·05) with a nadir at +24 h, comparable reduction at +48 h and recovery to baseline at +72 h. Deconvolution analysis showed that the antagonist peptide suppressed (P < 0·02) the pulsatile production rate, burst mass and amplitude of LH on day 1. Pulsatile FSH secretion also fell at this time (P < 0·05). LH and FSH pulse frequency were not modified by TEV. At +96 h, LH pulsatility did not significantly differ from that at baseline. Suppression of mean LH or FSH concentrations did not affect the relative pattern regularity (approximate entropy) of LH and FSH secretion.
conclusions This study demonstrates that the acute administration of a potent GnRH antagonist induces prompt inhibition of the gonadal axis lasting for 2 days in women due to mechanistically specific suppression of LH secretory burst mass and the mean FSH secretion rate. The trend toward rebound release of LH following the end of the pharmacological effect of the antagonist could reflect a rise in endogenous GnRH activity.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>14510918</pmid><doi>10.1046/j.1365-2265.2003.01882.x</doi><tpages>7</tpages></addata></record> |
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| ispartof | Clinical endocrinology (Oxford), 2003-10, Vol.59 (4), p.526-532 |
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| source | Wiley-Blackwell Read & Publish Collection |
| subjects | Adult Biological and medical sciences Endocrinopathies Estradiol - blood Female Follicle Stimulating Hormone - blood Follicle Stimulating Hormone - metabolism Follicular Phase - physiology Fundamental and applied biological sciences. Psychology Hormone Antagonists - pharmacology Humans Injections, Subcutaneous Luteinizing Hormone - blood Luteinizing Hormone - metabolism Medical sciences Oligopeptides - pharmacology Ovary - drug effects Radioimmunoassay - methods Receptors, LHRH - antagonists & inhibitors Secretory Rate - drug effects Time Factors Vertebrates: endocrinology |
| title | Suppression and recovery of LH secretion by a potent and selective GnRH-receptor antagonist peptide in healthy early follicular-phase women are mediated via selective control of LH secretory burst mass |
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