Mechanisms underlying the diminished sensitivity to prolactin negative feedback during lactation: Reduced STAT5 signaling and up-regulation of cytokine-inducible SH2 domain-containing protein (CIS) expression in tuberoinfundibular dopaminergic neurons

Anderson, Stephen T., Barclay, Johanna L., Fanning, Kent J., Kusters, Daphne H. L., Waters, Michael J. and Curlewis, Jon D. (2006) Mechanisms underlying the diminished sensitivity to prolactin negative feedback during lactation: Reduced STAT5 signaling and up-regulation of cytokine-inducible SH2 domain-containing protein (CIS) expression in tuberoinfundibular dopaminergic neurons. Endocrinology, 147 3: 1195-1202. doi:10.1210/en.2005-0905

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Author Anderson, Stephen T.
Barclay, Johanna L.
Fanning, Kent J.
Kusters, Daphne H. L.
Waters, Michael J.
Curlewis, Jon D.
Title Mechanisms underlying the diminished sensitivity to prolactin negative feedback during lactation: Reduced STAT5 signaling and up-regulation of cytokine-inducible SH2 domain-containing protein (CIS) expression in tuberoinfundibular dopaminergic neurons
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 2006-01-01
Year available 2006
Sub-type Article (original research)
DOI 10.1210/en.2005-0905
Open Access Status File (Author Post-print)
Volume 147
Issue 3
Start page 1195
End page 1202
Total pages 8
Editor Kenneth Korach
Place of publication Bethesda, MA, U.S.A.
Publisher The Endocrine Society
Language eng
Subject C1
270603 Animal Physiology - Systems
321004 Endocrinology
1105 Dentistry
Abstract Hyperprolactinaemia during lactation is a consequence of the sucking stimulus and in part due to reduced prolactin (PRL) negative feedback. To date, the mechanisms involved in this diminished sensitivity to PRL feedback are unknown but may involve changes in PRL signal transduction within tuberoinfundibular dopaminergic (TIDA) neurons. Therefore, we investigated signal transducers and activators of transcription (STAT) 5 signaling in the TIDA neurons of lactating rats. Dual-label confocal immunofluorescence studies were used to determine the intracellular distribution of STAT5 within TIDA neurons in the dorsomedial arcuate nucleus. In lactating rats with pups removed for 16 h, injection of ovine PRL significantly (P < 0.05) increased the STAT5 nuclear/cytoplasmic ratio compared with vehicle-treated mothers. In contrast, ovine PRL injection did not increase the STAT5 nuclear/cytoplasmic ratio in lactating mothers with pups, demonstrating that PRL signal transduction through STAT5 is reduced in TIDA neurons in the presence of pups. To investigate possible mechanisms involved in reduced PRL signaling, we examined the expression of suppressors of cytokine signaling (SOCS) proteins. Northern analysis on whole hypothalamus showed that CIS (cytokine-inducible SH2 domain-containing protein), but not SOCS1 or SOCS3, mRNA expression was significantly (P < 0.01) up-regulated in suckled lactating rats. Semiquantitative RT-PCR on arcuate nucleus micropunches also showed up-regulation of CIS transcripts. Immunofluorescence studies demonstrated that CIS is expressed in all TIDA neurons in the dorsomedial arcuate nucleus, and the intensity of CIS staining in these neurons is significantly (P < 0.05) increased in lactating rats with sucking pups. Together, these results support the hypothesis that loss of sensitivity to PRL-negative feedback during lactation is a result of increased CIS expression in TIDA neurons.
Keyword Endocrinology & Metabolism
Receptor Immunoreactivity
Prl
Rat
Suppressors
Secretion
Hypothalamus
Transduction
Activation
Induction
Growth
Q-Index Code C1
Institutional Status UQ

 
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