Tissue-specific induction of SOCS gene expression by PRL.
The mechanisms whereby tissue sensitivity to PRL is controlled are not well understood. Here we report that expression of mRNA and protein for members of the SOCS/CIS/JAB family of cytokine signaling inhibitors is increased by PRL administration in ovary and adrenal gland of the lactating rat deprived of circulating PRL and pups for 24 h but not in mammary gland. Moreover, suckling increases SOCS mRNA in the ovary but not in the mammary gland of pup-deprived rats. Deprivation of PRL and pups for 48 h allows the mammary gland to induce SOCS genes in response to PRL administration, and this is associated with a decrease in basal SOCS-3 mRNA and protein expression to the level seen in other tissues, suggesting that SOCS-3 induced refractoriness related to filling of the gland. In reporter assays, SOCS-1, SOCS-3, and CIS, but not SOCS-2, are able to inhibit transactivation of the STAT 5-responsive beta-lactoglobulin promoter in transient transfection assays. Moreover, suckling results in loss of ovarian and adrenal responsiveness to PRL administered 2 h after commencement of suckling, as determined by STAT 5 gel shift assay. Immunohistochemistry was used to localize the cellular sites of SOCS-3 and CIS protein expression in the ovary and adrenal gland. We propose that induced SOCS-1, SOCS-3, and CIS are actively involved in the cellular inhibitory feedback response to physiological PRL surges in the corpus luteum and adrenal cortex during lactation, but after pup withdrawal, the mammary gland is rendered unresponsive to PRL by increased levels of SOCS-3.
Tam
S P
SP
Department of Physiology and Pharmacology, and Institute for Molecular Bioscience, University of Queensland, St. Lucia, Brisbane 4072, Australia.
Lau
P
P
Djiane
J
J
Hilton
D J
DJ
Waters
M J
MJ
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000502:physiology; D007774:Lactation / Q000502:physiology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism; D008894:Milk Proteins; D010053:Ovary / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology / Q000502:physiology*; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D012756:Sheep; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D008894:Milk Proteins; D011388:Prolactin; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C491589:Socs1 protein, rat; C491408:Socs2 protein, rat; C491410:Socs3 protein, rat