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Am J Physiol Endocrinol Metab (January 22, 2002). doi:10.1152/ajpendo.00442.2001
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Articles in PresS, published online ahead of print January 22, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00442.2001
Submitted on October 4, 2001
Accepted on January 11, 2002

Opposing effects of pituitary leukemia inhibitory factor and SOCS 3 on the ACTH axis response to inflammation

Vera Chesnokova1*, Anastasia Kariagina1, and Shlomo Melmed1

1 Medicine/Endocrinology, Cedars-Sinai Research Institute-UCLA School of Medicine, Los Angeles, CA, USA

* To whom correspondence should be addressed. E-mail: chesnokovav{at}cshs.org.

We have shown that leukemia inhibitory factor (LIF) and SOCS 3 are expressed in the hypothalamus and pituitary, and that LIF induces POMC and ACTH, while SOCS 3 abrogates corticotroph POMC gene transcription and ACTH secretion. Here we determined the role of pituitary LIF and SOCS 3 in regulating HPA axis inflammatory responses. Murine pituitary LIF expression was induced up to 8-fold after ip injection of LPS or TNF {alpha}, concordant with elevated plasma levels of ACTH and corticosterone. In LIF knockout mice (LIFKO), induction of both ACTH and corticosterone were attenuated. LIF deletion was associated with elevated (p<0.05) levels of pituitary TNF{alpha}, IL 1ß and IL 6 mRNA and cytokine-inducible pituitary SOCS 3 expression. Abrogation of the HPA axis stress response, and higher pituitary levels of proinflammatory cytokines observed in LIFKO mice resulted in a stronger inflammatory process as evident by elevated ESR and increased serum amyloid A levels (p<0.05). The results indicate that while LIF induces ACTH, SOCS 3 acts to counter-regulate the HPA axis response to inflammation.




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