Hormonal regulation of suppressors of cytokine signaling expression in the arcuate nucleus during late pregnancy

Steyn, Frederik J., Anderson, Greg M. and Grattan, David R. (2008) Hormonal regulation of suppressors of cytokine signaling expression in the arcuate nucleus during late pregnancy. Endocrinology, 149 6: 3206-3214. doi:10.1210/en.2007-1623

Author Steyn, Frederik J.
Anderson, Greg M.
Grattan, David R.
Title Hormonal regulation of suppressors of cytokine signaling expression in the arcuate nucleus during late pregnancy
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 2008-06
Sub-type Article (original research)
DOI 10.1210/en.2007-1623
Volume 149
Issue 6
Start page 3206
End page 3214
Total pages 9
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Language eng
Subject 11 Medical and Health Sciences
110306 Endocrinology
Abstract Prolactin stimulates tuberoinfundibular dopamine neurons in the arcuate nucleus of the hypothalamus, mediated by signal transducer and activator of transcription 5b (STAT5b). During late pregnancy, these neurons become unresponsive to prolactin, with a loss of prolactin-induced activation of STAT5b and decreased dopamine secretion. Suppressors of cytokine signaling (SOCS) proteins inhibit STAT-mediated signaling, and SOCS mRNAs are specifically elevated in the arcuate nucleus during late pregnancy. We hypothesized that changes in circulating ovarian steroids during late pregnancy might induce expression of SOCS mRNAs, thus disrupting STAT5b-mediated prolactin signaling. Rats were ovariectomized on d 18 of pregnancy and treated with ovarian steroids to simulate an advanced, normal, or delayed decline in progesterone. Early progesterone withdrawal caused an early increase in prolactin secretion, and increased SOCS-1 and -3 and cytokine-inducible SH2-containing protein (CIS) mRNA levels in the arcuate nucleus. Prolonged progesterone treatment prevented these changes. To determine whether ovarian steroids directly alter SOCS mRNA levels, estrogen- and/or progesterone-treated ovariectomized nonpregnant rats were acutely injected with prolactin (300 g sc) or vehicle. SOCS-1 and -3 and CIS mRNA levels in the arcuate nucleus were significantly increased by estrogen or prolactin, whereas progesterone treatment reversed the effect of estrogen. Results demonstrate that estrogen and prolactin can independently induce SOCSmRNAin the arcuate nucleus and that this effect is negatively regulated by progesterone. This is consistent with the hypothesis that declining progesterone and high levels of estrogen during late pregnancy induce SOCS in the tuberoinfundibular dopamine neurons, thus contributing to their insensitivity to prolactin at this time.
Keyword Endocrinology
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
ERA 2012 Admin Only
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
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