Prolactin transport into mouse brain is independent of prolactin receptor
The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood‐brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it...
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| Veröffentlicht in: | The FASEB journal 2016-02, Vol.30 (2), p.1002-1010 |
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| description | The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood‐brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF). This study aimed to test this hypothesis by investigating transport of 125I‐labeled prolactin (125I‐prolactin) into the brain of female mice in the presence and absence of the prolactin receptor (PRLR–/–). Peripherally administered prolactin rapidly activates brain neurons, as evidenced by prolactin‐induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) in neurons within 30 min of administration. The transport of prolactin into the brain was saturable, with transport effectively blocked only by a very high dose of unlabeled ovine prolactin. Transport was regulated, as in lactating mice with chronically elevated levels of prolactin, the rate of 125I‐prolactin transport into the brain was significantly increased compared to non‐lactating controls. There was no change in the rate of 125I‐prolactin transport into the brain in PRLR–/– mice lacking functional prolactin receptors compared to control mice, indicating transport is independent of the prolactin receptor. These data suggest that prolactin transport into the brain involves another as yet unidentified transporter molecule. Because CSF levels of 125I‐prolactin were very low, even up to 90 min after administration, the data suggest that CSF is not the major route by which blood prolactin gains access to neurons in the brain.—Brown, R. S. E., Wyatt, A. K., Herbison, R. E., Knowles, P. J., Ladyman, S. R., Binart, N., Banks, W. A., Grattan, D. R. Prolactin transport into mouse brain is independent of prolactin receptor. FASEB J. 30, 1002–1010 (2016). www.fasebj.org |
| doi_str_mv | 10.1096/fj.15-276519 |
| format | Article |
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E. ; Wyatt, Amanda K. ; Herbison, Ryan E. ; Knowles, Penelope J. ; Ladyman, Sharon R. ; Binart, Nadine ; Banks, William A. ; Grattan, David R.</creator><creatorcontrib>Brown, Rosemary S. E. ; Wyatt, Amanda K. ; Herbison, Ryan E. ; Knowles, Penelope J. ; Ladyman, Sharon R. ; Binart, Nadine ; Banks, William A. ; Grattan, David R.</creatorcontrib><description>The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood‐brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF). This study aimed to test this hypothesis by investigating transport of 125I‐labeled prolactin (125I‐prolactin) into the brain of female mice in the presence and absence of the prolactin receptor (PRLR–/–). Peripherally administered prolactin rapidly activates brain neurons, as evidenced by prolactin‐induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) in neurons within 30 min of administration. The transport of prolactin into the brain was saturable, with transport effectively blocked only by a very high dose of unlabeled ovine prolactin. Transport was regulated, as in lactating mice with chronically elevated levels of prolactin, the rate of 125I‐prolactin transport into the brain was significantly increased compared to non‐lactating controls. There was no change in the rate of 125I‐prolactin transport into the brain in PRLR–/– mice lacking functional prolactin receptors compared to control mice, indicating transport is independent of the prolactin receptor. These data suggest that prolactin transport into the brain involves another as yet unidentified transporter molecule. Because CSF levels of 125I‐prolactin were very low, even up to 90 min after administration, the data suggest that CSF is not the major route by which blood prolactin gains access to neurons in the brain.—Brown, R. S. E., Wyatt, A. K., Herbison, R. E., Knowles, P. J., Ladyman, S. R., Binart, N., Banks, W. A., Grattan, D. R. Prolactin transport into mouse brain is independent of prolactin receptor. 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E.</creatorcontrib><creatorcontrib>Wyatt, Amanda K.</creatorcontrib><creatorcontrib>Herbison, Ryan E.</creatorcontrib><creatorcontrib>Knowles, Penelope J.</creatorcontrib><creatorcontrib>Ladyman, Sharon R.</creatorcontrib><creatorcontrib>Binart, Nadine</creatorcontrib><creatorcontrib>Banks, William A.</creatorcontrib><creatorcontrib>Grattan, David R.</creatorcontrib><title>Prolactin transport into mouse brain is independent of prolactin receptor</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood‐brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF). This study aimed to test this hypothesis by investigating transport of 125I‐labeled prolactin (125I‐prolactin) into the brain of female mice in the presence and absence of the prolactin receptor (PRLR–/–). Peripherally administered prolactin rapidly activates brain neurons, as evidenced by prolactin‐induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) in neurons within 30 min of administration. The transport of prolactin into the brain was saturable, with transport effectively blocked only by a very high dose of unlabeled ovine prolactin. Transport was regulated, as in lactating mice with chronically elevated levels of prolactin, the rate of 125I‐prolactin transport into the brain was significantly increased compared to non‐lactating controls. There was no change in the rate of 125I‐prolactin transport into the brain in PRLR–/– mice lacking functional prolactin receptors compared to control mice, indicating transport is independent of the prolactin receptor. These data suggest that prolactin transport into the brain involves another as yet unidentified transporter molecule. Because CSF levels of 125I‐prolactin were very low, even up to 90 min after administration, the data suggest that CSF is not the major route by which blood prolactin gains access to neurons in the brain.—Brown, R. S. E., Wyatt, A. K., Herbison, R. E., Knowles, P. J., Ladyman, S. R., Binart, N., Banks, W. A., Grattan, D. R. Prolactin transport into mouse brain is independent of prolactin receptor. FASEB J. 30, 1002–1010 (2016). www.fasebj.org</description><subject>Animals</subject><subject>blood‐brain barrier</subject><subject>Brain - metabolism</subject><subject>choroid plexus</subject><subject>Female</subject><subject>lactation</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neurons - metabolism</subject><subject>Prolactin - genetics</subject><subject>Prolactin - metabolism</subject><subject>Protein Transport - physiology</subject><subject>Receptors, Prolactin - genetics</subject><subject>Receptors, Prolactin - metabolism</subject><subject>STAT5 Transcription Factor - genetics</subject><subject>STAT5 Transcription Factor - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFLwzAUh4Mobk5vnqVHD3a-JE3SHHU4HQwU1HNI0gQ6urYmHbL_3kjnjl7eg_e-9-PxIXSNYY5B8nu_mWOWE8EZlidoihmFnJccTtEUSklyzmk5QRcxbgAAA-bnaEI44wKATdHqLXSNtkPdZkPQbey7MGR1O3TZtttFl5mg06qOaVa53qXSDlnns_54Fpx1_dCFS3TmdRPd1aHP0Ofy6WPxkq9fn1eLh3VuKZUiN5gAAcGxI9wyXHlrSkFKCb4ylfHacWOw1JyXpPSSClYISSqpS4Kt80zSGbodc9MLXzsXB7Wto3VNo1uXXlZYcEKLAjhN6N2I2tDFGJxXfai3OuwVBvUrT_mNwkyN8hJ-c0jema2rjvCfrQSIEfiuG7f_N0wt3x8J0KScQCHoDyhLepo</recordid><startdate>201602</startdate><enddate>201602</enddate><creator>Brown, Rosemary S. 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E. ; Wyatt, Amanda K. ; Herbison, Ryan E. ; Knowles, Penelope J. ; Ladyman, Sharon R. ; Binart, Nadine ; Banks, William A. ; Grattan, David R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3397-b12020761e26c51dfcb872890fdbdbfae6bb19a66828f93754792d9a821cef593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>blood‐brain barrier</topic><topic>Brain - metabolism</topic><topic>choroid plexus</topic><topic>Female</topic><topic>lactation</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neurons - metabolism</topic><topic>Prolactin - genetics</topic><topic>Prolactin - metabolism</topic><topic>Protein Transport - physiology</topic><topic>Receptors, Prolactin - genetics</topic><topic>Receptors, Prolactin - metabolism</topic><topic>STAT5 Transcription Factor - genetics</topic><topic>STAT5 Transcription Factor - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brown, Rosemary S. E.</creatorcontrib><creatorcontrib>Wyatt, Amanda K.</creatorcontrib><creatorcontrib>Herbison, Ryan E.</creatorcontrib><creatorcontrib>Knowles, Penelope J.</creatorcontrib><creatorcontrib>Ladyman, Sharon R.</creatorcontrib><creatorcontrib>Binart, Nadine</creatorcontrib><creatorcontrib>Banks, William A.</creatorcontrib><creatorcontrib>Grattan, David R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brown, Rosemary S. E.</au><au>Wyatt, Amanda K.</au><au>Herbison, Ryan E.</au><au>Knowles, Penelope J.</au><au>Ladyman, Sharon R.</au><au>Binart, Nadine</au><au>Banks, William A.</au><au>Grattan, David R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prolactin transport into mouse brain is independent of prolactin receptor</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2016-02</date><risdate>2016</risdate><volume>30</volume><issue>2</issue><spage>1002</spage><epage>1010</epage><pages>1002-1010</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>The anterior pituitary hormone prolactin exerts important physiologic actions in the brain. However, the mechanism by which prolactin crosses the blood‐brain barrier and enters the brain is not completely understood. On the basis of high expression of the prolactin receptor in the choroid plexus, it has been hypothesized that the receptor may bind to prolactin in the blood and translocate it into the cerebrospinal fluid (CSF). This study aimed to test this hypothesis by investigating transport of 125I‐labeled prolactin (125I‐prolactin) into the brain of female mice in the presence and absence of the prolactin receptor (PRLR–/–). Peripherally administered prolactin rapidly activates brain neurons, as evidenced by prolactin‐induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) in neurons within 30 min of administration. The transport of prolactin into the brain was saturable, with transport effectively blocked only by a very high dose of unlabeled ovine prolactin. Transport was regulated, as in lactating mice with chronically elevated levels of prolactin, the rate of 125I‐prolactin transport into the brain was significantly increased compared to non‐lactating controls. There was no change in the rate of 125I‐prolactin transport into the brain in PRLR–/– mice lacking functional prolactin receptors compared to control mice, indicating transport is independent of the prolactin receptor. These data suggest that prolactin transport into the brain involves another as yet unidentified transporter molecule. Because CSF levels of 125I‐prolactin were very low, even up to 90 min after administration, the data suggest that CSF is not the major route by which blood prolactin gains access to neurons in the brain.—Brown, R. S. E., Wyatt, A. K., Herbison, R. E., Knowles, P. J., Ladyman, S. R., Binart, N., Banks, W. A., Grattan, D. R. Prolactin transport into mouse brain is independent of prolactin receptor. 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| subjects | Animals blood‐brain barrier Brain - metabolism choroid plexus Female lactation Male Mice Mice, Knockout Neurons - metabolism Prolactin - genetics Prolactin - metabolism Protein Transport - physiology Receptors, Prolactin - genetics Receptors, Prolactin - metabolism STAT5 Transcription Factor - genetics STAT5 Transcription Factor - metabolism |
| title | Prolactin transport into mouse brain is independent of prolactin receptor |
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