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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. 2006 Mar; 147(3):1195-202.E

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.

Authors+Show Affiliations

School of Biomedical Sciences, The University of Queensland, Queensland 4072, Australia. stephen.anderson@uq.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16357045

Citation

Anderson, Stephen T., et al. "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, vol. 147, no. 3, 2006, pp. 1195-202.
Anderson ST, Barclay JL, Fanning KJ, et al. 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. 2006;147(3):1195-202.
Anderson, S. T., Barclay, J. L., Fanning, K. J., Kusters, D. H., Waters, M. J., & Curlewis, J. 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), 1195-202.
Anderson ST, et al. 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. 2006;147(3):1195-202. PubMed PMID: 16357045.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Anderson,Stephen T, AU - Barclay,Johanna L, AU - Fanning,Kent J, AU - Kusters,Daphne H L, AU - Waters,Michael J, AU - Curlewis,Jon D, Y1 - 2005/12/15/ PY - 2005/12/17/pubmed PY - 2006/4/14/medline PY - 2005/12/17/entrez SP - 1195 EP - 202 JF - Endocrinology JO - Endocrinology VL - 147 IS - 3 N2 - 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. SN - 0013-7227 UR - https://www.unboundmedicine.com/medline/citation/16357045/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_ DB - PRIME DP - Unbound Medicine ER -