Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female Rats
Prolactin (PRL) regulates its own secretion by short-loop feedback to tuberoinfundibular dopaminergic (TIDA) neurons. PRL-induced cellular mechanisms in the regulation of tyrosine hydroxylase (TH) are not completely understood. The objectives were to (1) examine PRL-induced, time-dependent hypothala...
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2025-04-01
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| author | Philip J. Jensik Lydia A. Arbogast |
| author_facet | Philip J. Jensik Lydia A. Arbogast |
| author_sort | Philip J. Jensik |
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| description | Prolactin (PRL) regulates its own secretion by short-loop feedback to tuberoinfundibular dopaminergic (TIDA) neurons. PRL-induced cellular mechanisms in the regulation of tyrosine hydroxylase (TH) are not completely understood. The objectives were to (1) examine PRL-induced, time-dependent hypothalamic changes in JAK2-STAT5B signaling, TH activity, TH phosphorylation state and <i>Th</i> mRNA levels, and (2) evaluate direct influences of PRLR-STAT5B signaling on <i>Th</i> promoter activity. Ovariectomized rats were administered ovine PRL. JAK2 and STAT5 phosphorylation in the mediobasal hypothalamus peaked at 15 and 30–60 min, respectively. TH Ser40 phosphorylation in the median eminence was increased between 2 and 72 h, correlating with increased dihydroxyphenylalanine (DOPA) accumulation. <i>Th</i> mRNA levels in TIDA neurons were unchanged up to 72 h but elevated by 7 days. PRL did not alter <i>Th</i> promoter activity in CAD cells, and STAT5B did not bind three putative Gamma Interferon Activation Sites (GAS) elements. We conclude that PRL initiates an integrated cascade of cellular mechanisms in TIDA neurons, including JAK2-STAT5B activation, TH Ser40 phosphorylation coupled to increased TH activity, followed by a delayed rise in <i>Th</i> gene expression. PRL-induced changes in <i>Th</i> gene expression are not the result of STAT5-mediated transactivation but likely result from enduring changes in TIDA neuronal activity. |
| format | Article |
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| institution | OA Journals |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-fdae1724190e489d95c360438f35a9132025-08-20T02:24:47ZengMDPI AGCells2073-44092025-04-0114964210.3390/cells14090642Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female RatsPhilip J. Jensik0Lydia A. Arbogast1Division of Molecular and Integrative Physiology, Department of Biomedical Science, Southern Illinois University School of Medicine, Carbondale, IL 62901-6523, USADivision of Molecular and Integrative Physiology, Department of Biomedical Science, Southern Illinois University School of Medicine, Carbondale, IL 62901-6523, USAProlactin (PRL) regulates its own secretion by short-loop feedback to tuberoinfundibular dopaminergic (TIDA) neurons. PRL-induced cellular mechanisms in the regulation of tyrosine hydroxylase (TH) are not completely understood. The objectives were to (1) examine PRL-induced, time-dependent hypothalamic changes in JAK2-STAT5B signaling, TH activity, TH phosphorylation state and <i>Th</i> mRNA levels, and (2) evaluate direct influences of PRLR-STAT5B signaling on <i>Th</i> promoter activity. Ovariectomized rats were administered ovine PRL. JAK2 and STAT5 phosphorylation in the mediobasal hypothalamus peaked at 15 and 30–60 min, respectively. TH Ser40 phosphorylation in the median eminence was increased between 2 and 72 h, correlating with increased dihydroxyphenylalanine (DOPA) accumulation. <i>Th</i> mRNA levels in TIDA neurons were unchanged up to 72 h but elevated by 7 days. PRL did not alter <i>Th</i> promoter activity in CAD cells, and STAT5B did not bind three putative Gamma Interferon Activation Sites (GAS) elements. We conclude that PRL initiates an integrated cascade of cellular mechanisms in TIDA neurons, including JAK2-STAT5B activation, TH Ser40 phosphorylation coupled to increased TH activity, followed by a delayed rise in <i>Th</i> gene expression. PRL-induced changes in <i>Th</i> gene expression are not the result of STAT5-mediated transactivation but likely result from enduring changes in TIDA neuronal activity.https://www.mdpi.com/2073-4409/14/9/642prolactindopamineTIDAprolactin receptor signalingtyrosine hydroxylasephosphorylation |
| spellingShingle | Philip J. Jensik Lydia A. Arbogast Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female Rats Cells prolactin dopamine TIDA prolactin receptor signaling tyrosine hydroxylase phosphorylation |
| title | Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female Rats |
| title_full | Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female Rats |
| title_fullStr | Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female Rats |
| title_full_unstemmed | Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female Rats |
| title_short | Prolactin Mediates Distinct Time Course Regulation of Tyrosine Hydroxylase Phosphorylation and Gene Expression in Tuberoinfundibular Dopaminergic Neurons of Female Rats |
| title_sort | prolactin mediates distinct time course regulation of tyrosine hydroxylase phosphorylation and gene expression in tuberoinfundibular dopaminergic neurons of female rats |
| topic | prolactin dopamine TIDA prolactin receptor signaling tyrosine hydroxylase phosphorylation |
| url | https://www.mdpi.com/2073-4409/14/9/642 |
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