Alcohol Delays the Onset of Puberty in the Female Rat by Altering Key Hypothalamic Events
Background Because alcohol (ALC) delays signs of pubertal development, we assessed the time course of events associated with the synthesis of critical hypothalamic peptides that regulate secretion of luteinizing hormone‐releasing hormone (LHRH), the peptide that drives the pubertal process. Methods...
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| Veröffentlicht in: | Alcoholism, clinical and experimental research clinical and experimental research, 2018-07, Vol.42 (7), p.1166-1176 |
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| creator | Srivastava, Vinod K. Hiney, Jill K. Dees, William L. |
| description | Background
Because alcohol (ALC) delays signs of pubertal development, we assessed the time course of events associated with the synthesis of critical hypothalamic peptides that regulate secretion of luteinizing hormone‐releasing hormone (LHRH), the peptide that drives the pubertal process.
Methods
Immature female rats were administered either laboratory chow or BioServe isocaloric control or ALC‐liquid diets from 27 through 33 days of age. On days 28, 29, 31, and 33, animals were killed by decapitation and tissue blocks containing the medial basal hypothalamus (MBH) and the rostral hypothalamic area (RHA) were isolated and stored frozen until assessed by Western blot analysis.
Results
Synthesis of dynorphin (DYN), a prepubertal inhibitor of LHRH secretion, was increased (p |
| doi_str_mv | 10.1111/acer.13762 |
| format | Article |
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Because alcohol (ALC) delays signs of pubertal development, we assessed the time course of events associated with the synthesis of critical hypothalamic peptides that regulate secretion of luteinizing hormone‐releasing hormone (LHRH), the peptide that drives the pubertal process.
Methods
Immature female rats were administered either laboratory chow or BioServe isocaloric control or ALC‐liquid diets from 27 through 33 days of age. On days 28, 29, 31, and 33, animals were killed by decapitation and tissue blocks containing the medial basal hypothalamus (MBH) and the rostral hypothalamic area (RHA) were isolated and stored frozen until assessed by Western blot analysis.
Results
Synthesis of dynorphin (DYN), a prepubertal inhibitor of LHRH secretion, was increased (p < 0.05) in the MBH of ALC‐treated animals by day 29. DYN was further elevated (p < 0.01) on day 33 and was associated with an increase (p < 0.01) in DYN receptor expression. ALC did not affect synthesis of neurokinin B (NKB), a prepubertal stimulator of LHRH; however, it did suppress (p < 0.05) NKB receptor expression in the MBH by day 31. The most potent stimulator of prepubertal LHRH secretion, kisspeptin (Kp), was also decreased (p < 0.05) in the MBH as early as day 29, with continued suppression (p < 0.01) through day 33. Similar timely suppressions of mammalian target of rapamycin (mTOR), an immediate upstream regulator of Kp, were also noted. These decreases in mTOR and Kp were consistent with ALC stimulating (p < 0.05) the p‐AMP‐activated protein kinase/Raptor inhibitory pathway to mTOR on day 29, then later suppressing (p < 0.001) an Akt‐mediated induction pathway to mTOR by day 31. In the RHA, ALC affected the pathways regulating Kp in a manner similar to that described in the MBH; however, these effects were not noted until day 33.
Conclusions
ALC acts within the MBH as early as 29 days to induce inhibitor and repressor inputs to LHRH, while depressing stimulatory inputs to the peptide. Collectively, these events lead to delayed signs of pubertal development.
Our study shows the timing of ALC effects resulting in delayed signs of pubertal development. In the medial basal hypothalamus (MBH), ALC stimulated dynorphin (DYN), as well as the p‐AMP protein kinase α (AMPKα)/p‐Raptor pathway by day 29; hence, suppressing kisspeptin (KP) control of LHRH secretion. In the rostral hypothalamic area (RHA), there were no effects of ALC until day 33, at which time it suppressed the insulin‐like growth factor 1 receptor (IGF‐1R)/ p‐Akt pathway to kisspeptin (Kp) and thus, further suppressed the LHRH needed to enter first proestrus.]]></description><identifier>ISSN: 0145-6008</identifier><identifier>EISSN: 1530-0277</identifier><identifier>DOI: 10.1111/acer.13762</identifier><identifier>PMID: 29689132</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>AKT protein ; Alcohol ; Alcohol use ; Alcohols ; AMP ; Animals ; Developmental biology ; Dynorphin ; Gonadotropin-releasing hormone ; Hypothalamus ; Hypothalamus (medial) ; Kinases ; Kiss1 protein ; Kisspeptin ; Luteinizing hormone ; Neurokinin ; Neurokinin B ; Peptides ; Protein kinase ; Puberty ; Rapamycin ; Rodents ; Secretion ; Stimulators ; TOR protein</subject><ispartof>Alcoholism, clinical and experimental research, 2018-07, Vol.42 (7), p.1166-1176</ispartof><rights>Copyright © 2018 by the Research Society on Alcoholism</rights><rights>Copyright © 2018 by the Research Society on Alcoholism.</rights><rights>2018 Research Society on Alcoholism</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4482-d5c66e2b55df8c93cb5ca5ed0eec4724aeeb5a8ea953cef831421bc5465e06073</citedby><cites>FETCH-LOGICAL-c4482-d5c66e2b55df8c93cb5ca5ed0eec4724aeeb5a8ea953cef831421bc5465e06073</cites><orcidid>0000-0001-9286-9229</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Facer.13762$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Facer.13762$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29689132$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Srivastava, Vinod K.</creatorcontrib><creatorcontrib>Hiney, Jill K.</creatorcontrib><creatorcontrib>Dees, William L.</creatorcontrib><title>Alcohol Delays the Onset of Puberty in the Female Rat by Altering Key Hypothalamic Events</title><title>Alcoholism, clinical and experimental research</title><addtitle>Alcohol Clin Exp Res</addtitle><description><![CDATA[Background
Because alcohol (ALC) delays signs of pubertal development, we assessed the time course of events associated with the synthesis of critical hypothalamic peptides that regulate secretion of luteinizing hormone‐releasing hormone (LHRH), the peptide that drives the pubertal process.
Methods
Immature female rats were administered either laboratory chow or BioServe isocaloric control or ALC‐liquid diets from 27 through 33 days of age. On days 28, 29, 31, and 33, animals were killed by decapitation and tissue blocks containing the medial basal hypothalamus (MBH) and the rostral hypothalamic area (RHA) were isolated and stored frozen until assessed by Western blot analysis.
Results
Synthesis of dynorphin (DYN), a prepubertal inhibitor of LHRH secretion, was increased (p < 0.05) in the MBH of ALC‐treated animals by day 29. DYN was further elevated (p < 0.01) on day 33 and was associated with an increase (p < 0.01) in DYN receptor expression. ALC did not affect synthesis of neurokinin B (NKB), a prepubertal stimulator of LHRH; however, it did suppress (p < 0.05) NKB receptor expression in the MBH by day 31. The most potent stimulator of prepubertal LHRH secretion, kisspeptin (Kp), was also decreased (p < 0.05) in the MBH as early as day 29, with continued suppression (p < 0.01) through day 33. Similar timely suppressions of mammalian target of rapamycin (mTOR), an immediate upstream regulator of Kp, were also noted. These decreases in mTOR and Kp were consistent with ALC stimulating (p < 0.05) the p‐AMP‐activated protein kinase/Raptor inhibitory pathway to mTOR on day 29, then later suppressing (p < 0.001) an Akt‐mediated induction pathway to mTOR by day 31. In the RHA, ALC affected the pathways regulating Kp in a manner similar to that described in the MBH; however, these effects were not noted until day 33.
Conclusions
ALC acts within the MBH as early as 29 days to induce inhibitor and repressor inputs to LHRH, while depressing stimulatory inputs to the peptide. Collectively, these events lead to delayed signs of pubertal development.
Our study shows the timing of ALC effects resulting in delayed signs of pubertal development. In the medial basal hypothalamus (MBH), ALC stimulated dynorphin (DYN), as well as the p‐AMP protein kinase α (AMPKα)/p‐Raptor pathway by day 29; hence, suppressing kisspeptin (KP) control of LHRH secretion. In the rostral hypothalamic area (RHA), there were no effects of ALC until day 33, at which time it suppressed the insulin‐like growth factor 1 receptor (IGF‐1R)/ p‐Akt pathway to kisspeptin (Kp) and thus, further suppressed the LHRH needed to enter first proestrus.]]></description><subject>AKT protein</subject><subject>Alcohol</subject><subject>Alcohol use</subject><subject>Alcohols</subject><subject>AMP</subject><subject>Animals</subject><subject>Developmental biology</subject><subject>Dynorphin</subject><subject>Gonadotropin-releasing hormone</subject><subject>Hypothalamus</subject><subject>Hypothalamus (medial)</subject><subject>Kinases</subject><subject>Kiss1 protein</subject><subject>Kisspeptin</subject><subject>Luteinizing hormone</subject><subject>Neurokinin</subject><subject>Neurokinin B</subject><subject>Peptides</subject><subject>Protein kinase</subject><subject>Puberty</subject><subject>Rapamycin</subject><subject>Rodents</subject><subject>Secretion</subject><subject>Stimulators</subject><subject>TOR protein</subject><issn>0145-6008</issn><issn>1530-0277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kUFrFDEYhoModq1e_AES8CLCtF8ySSZzEZbt1oqFStGDp5DJftOdkpmsyUzL_HvTbi3qod8l8OXhyRteQt4yOGJ5jq3DeMTKSvFnZMFkCQXwqnpOFsCELBSAPiCvUroGAKGVekkOeK10zUq-ID-X3oVt8PQEvZ0THbdIL4aEIw0t_TY1GMeZdsP9_hR765Fe2pE2M136EWM3XNGvONOzeRfGrfW27xxd3-AwptfkRWt9wjcP5yH5cbr-vjorzi8-f1ktzwsnhObFRjqlkDdSblrt6tI10lmJG0B0ouLCIjbSarS1LB22umSCs8ZJoSSCgqo8JJ_23t3U9Lhx-e1ovdnFrrdxNsF25t-boduaq3BjFPBs01nw4UEQw68J02j6Ljn03g4YpmQ4lFAzkJXM6Pv_0OswxSF_L1OKa4Ba8Ex93FMuhpQito9hGJi7xsxdY-a-sQy_-zv-I_qnogywPXDbeZyfUJnlan25l_4GXrKhKQ</recordid><startdate>201807</startdate><enddate>201807</enddate><creator>Srivastava, Vinod K.</creator><creator>Hiney, Jill K.</creator><creator>Dees, William L.</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>K7.</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9286-9229</orcidid></search><sort><creationdate>201807</creationdate><title>Alcohol Delays the Onset of Puberty in the Female Rat by Altering Key Hypothalamic Events</title><author>Srivastava, Vinod K. ; Hiney, Jill K. ; Dees, William L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4482-d5c66e2b55df8c93cb5ca5ed0eec4724aeeb5a8ea953cef831421bc5465e06073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>AKT protein</topic><topic>Alcohol</topic><topic>Alcohol use</topic><topic>Alcohols</topic><topic>AMP</topic><topic>Animals</topic><topic>Developmental biology</topic><topic>Dynorphin</topic><topic>Gonadotropin-releasing hormone</topic><topic>Hypothalamus</topic><topic>Hypothalamus (medial)</topic><topic>Kinases</topic><topic>Kiss1 protein</topic><topic>Kisspeptin</topic><topic>Luteinizing hormone</topic><topic>Neurokinin</topic><topic>Neurokinin B</topic><topic>Peptides</topic><topic>Protein kinase</topic><topic>Puberty</topic><topic>Rapamycin</topic><topic>Rodents</topic><topic>Secretion</topic><topic>Stimulators</topic><topic>TOR protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Srivastava, Vinod K.</creatorcontrib><creatorcontrib>Hiney, Jill K.</creatorcontrib><creatorcontrib>Dees, William L.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Criminal Justice (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alcoholism, clinical and experimental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Srivastava, Vinod K.</au><au>Hiney, Jill K.</au><au>Dees, William L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alcohol Delays the Onset of Puberty in the Female Rat by Altering Key Hypothalamic Events</atitle><jtitle>Alcoholism, clinical and experimental research</jtitle><addtitle>Alcohol Clin Exp Res</addtitle><date>2018-07</date><risdate>2018</risdate><volume>42</volume><issue>7</issue><spage>1166</spage><epage>1176</epage><pages>1166-1176</pages><issn>0145-6008</issn><eissn>1530-0277</eissn><abstract><![CDATA[Background
Because alcohol (ALC) delays signs of pubertal development, we assessed the time course of events associated with the synthesis of critical hypothalamic peptides that regulate secretion of luteinizing hormone‐releasing hormone (LHRH), the peptide that drives the pubertal process.
Methods
Immature female rats were administered either laboratory chow or BioServe isocaloric control or ALC‐liquid diets from 27 through 33 days of age. On days 28, 29, 31, and 33, animals were killed by decapitation and tissue blocks containing the medial basal hypothalamus (MBH) and the rostral hypothalamic area (RHA) were isolated and stored frozen until assessed by Western blot analysis.
Results
Synthesis of dynorphin (DYN), a prepubertal inhibitor of LHRH secretion, was increased (p < 0.05) in the MBH of ALC‐treated animals by day 29. DYN was further elevated (p < 0.01) on day 33 and was associated with an increase (p < 0.01) in DYN receptor expression. ALC did not affect synthesis of neurokinin B (NKB), a prepubertal stimulator of LHRH; however, it did suppress (p < 0.05) NKB receptor expression in the MBH by day 31. The most potent stimulator of prepubertal LHRH secretion, kisspeptin (Kp), was also decreased (p < 0.05) in the MBH as early as day 29, with continued suppression (p < 0.01) through day 33. Similar timely suppressions of mammalian target of rapamycin (mTOR), an immediate upstream regulator of Kp, were also noted. These decreases in mTOR and Kp were consistent with ALC stimulating (p < 0.05) the p‐AMP‐activated protein kinase/Raptor inhibitory pathway to mTOR on day 29, then later suppressing (p < 0.001) an Akt‐mediated induction pathway to mTOR by day 31. In the RHA, ALC affected the pathways regulating Kp in a manner similar to that described in the MBH; however, these effects were not noted until day 33.
Conclusions
ALC acts within the MBH as early as 29 days to induce inhibitor and repressor inputs to LHRH, while depressing stimulatory inputs to the peptide. Collectively, these events lead to delayed signs of pubertal development.
Our study shows the timing of ALC effects resulting in delayed signs of pubertal development. In the medial basal hypothalamus (MBH), ALC stimulated dynorphin (DYN), as well as the p‐AMP protein kinase α (AMPKα)/p‐Raptor pathway by day 29; hence, suppressing kisspeptin (KP) control of LHRH secretion. In the rostral hypothalamic area (RHA), there were no effects of ALC until day 33, at which time it suppressed the insulin‐like growth factor 1 receptor (IGF‐1R)/ p‐Akt pathway to kisspeptin (Kp) and thus, further suppressed the LHRH needed to enter first proestrus.]]></abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29689132</pmid><doi>10.1111/acer.13762</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-9286-9229</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete; Journals@Ovid Complete |
| subjects | AKT protein Alcohol Alcohol use Alcohols AMP Animals Developmental biology Dynorphin Gonadotropin-releasing hormone Hypothalamus Hypothalamus (medial) Kinases Kiss1 protein Kisspeptin Luteinizing hormone Neurokinin Neurokinin B Peptides Protein kinase Puberty Rapamycin Rodents Secretion Stimulators TOR protein |
| title | Alcohol Delays the Onset of Puberty in the Female Rat by Altering Key Hypothalamic Events |
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