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Tissue-specific induction of SOCS gene expression by PRL
1Department of Physiology and Pharmacology, and Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Endocrinology
|October 19, 2001
Summary
Prolactin (PRL) signaling is regulated by Suppressors of Cytokine Signaling (SOCS) proteins. Lactating rats show increased SOCS in the ovary and adrenal gland, but mammary gland refractoriness to PRL is linked to SOCS-3 after pup withdrawal.
Area of Science:
- Endocrinology
- Molecular Biology
- Reproductive Biology
Background:
- Tissue sensitivity to prolactin (PRL) is crucial during lactation but its regulatory mechanisms remain unclear.
- The Suppressors of Cytokine Signaling (SOCS) family, including CIS/JAB, are known cytokine signaling inhibitors.
Purpose of the Study:
- To investigate the role of SOCS/CIS/JAB proteins in regulating PRL sensitivity in lactating rats.
- To elucidate the impact of PRL, suckling, and pup deprivation on SOCS gene expression and PRL responsiveness in different tissues.
Main Methods:
- Quantitative analysis of SOCS/CIS/JAB mRNA and protein expression in response to PRL administration and suckling.
- Reporter assays to assess the inhibitory function of SOCS proteins on STAT 5-mediated gene transactivation.
- STAT 5 gel shift assays to determine PRL responsiveness in ovarian and adrenal tissues.
- Immunohistochemistry to localize SOCS-3 and CIS protein expression.
Main Results:
- PRL administration increased SOCS/CIS/JAB mRNA and protein in the ovary and adrenal gland, but not the mammary gland, of pup-deprived lactating rats.
- Suckling increased SOCS mRNA in the ovary but not the mammary gland.
- Mammary gland refractoriness to PRL after 48-hour pup deprivation was associated with decreased basal SOCS-3 expression.
- SOCS-1, SOCS-3, and CIS inhibited STAT 5-mediated beta-lactoglobulin promoter activity, while SOCS-2 did not.
- Suckling reduced ovarian and adrenal responsiveness to PRL.
Conclusions:
- Induced SOCS-1, SOCS-3, and CIS are actively involved in the feedback inhibition of PRL signaling in the corpus luteum and adrenal cortex during lactation.
- Mammary gland unresponsiveness to PRL following pup withdrawal is mediated by elevated SOCS-3 levels, suggesting a role in regulating lactation cessation.