title: Prolactin transport into mouse brain is independent of prolactin receptor.
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 (125)I-labeled prolactin ((125)I-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 (125)I-prolactin transport into the brain was significantly increased compared to nonlactating controls. There was no change in the rate of (125)I-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 (125)I-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.
authors.affiliation: *Centre for Neurendocrinology and Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; INSERM U1185, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France; Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington, USA; and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Rosemary S E
authors.initials: RS
authors.lastname: Brown
authors.affiliation: *Centre for Neurendocrinology and Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; INSERM U1185, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France; Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington, USA; and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Wyatt
authors.affiliation: *Centre for Neurendocrinology and Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; INSERM U1185, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France; Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington, USA; and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Herbison
authors.affiliation: *Centre for Neurendocrinology and Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; INSERM U1185, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France; Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington, USA; and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Knowles
authors.affiliation: *Centre for Neurendocrinology and Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; INSERM U1185, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France; Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington, USA; and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Ladyman
authors.affiliation: *Centre for Neurendocrinology and Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; INSERM U1185, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France; Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington, USA; and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
authors.affiliation: *Centre for Neurendocrinology and Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; INSERM U1185, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France; Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington, USA; and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
authors.affiliation: *Centre for Neurendocrinology and Department of Anatomy, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand; INSERM U1185, Faculté de Médecine Paris Sud, Le Kremlin-Bicêtre, France; Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care Center, Seattle, Washington, USA; and Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA dave.grattan@otago.ac.nz.
authors.forename: David R
authors.initials: DR
authors.lastname: Grattan
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D011388:Prolactin
keywords: blood-brain barrier; choroid plexus; lactation