Lack of cross-desensitization between leptin and prolactin signaling pathways despite the induction of suppressor of cytokine signaling 3 and PTP-1B

A. F. Roy, Y. Benomar, V. Bailleux, C. M. Vacher, A. Aubourg, A. Gertler, J. Djiane, Mohammed Taouis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Hyperprolactinemia and hyperleptinemia occur during gestation and lactation with marked hyperphagia associated with leptin resistance. Prolactin (PRL) induces the expression of orexigenic neuropeptide Y (NPY) through the activation of JAK-2/STAT-3 signaling pathway in hypothalamic paraventricular nucleus (PVN) leading to hyperphagia. PRL may also act through the inhibition of anorexigenic effiect of leptin via induction of suppressor of cytokine signaling 3 (SOCS-3). This paper aimed to co-localize PRL (PRL-R) and leptin (ObRb) receptors in the hypothalamus offernale rats and investigate the possible cross-desensitization between PRL-R and ObRb. We showed that: 1) PRL-R and ObRb are expressed in the PVN and co-localized in the same neurons; 2) in lactating females leptin failed to activate JAK-2/STAT-3 signaling pathway; 3) in Chinese Hamster Ovary (CHO) stably co-expressing PRL-R and ObRb, overexposure to PRL did not afFect leptin signaling but totally abolished PRI-dependent STAT-5 phosphorylation. The overexposure to leptin produces similar results with strong alteration of leptin-dependent STAT-3 phosphorylation, whereas PRL-dependent STAT-5 was not affected; and 4) CHO-ObRb/PRL-R cells overexposure to leptin or PRL induces the expression of negative regulators SOCS-3 and PTP-1B. Thus, we conclude that these negative regulators afFect specifically the inducer signaling pathway; for instance, SOCS-3 induced by PRL will affect PRL-R signaling but not ObRb signaling and vice versa. Finally, the lack of cross-desensitization between PPL-R and ObRb suggests that hyperphagia observed during gestation and lactation may be attributed to a direct effect of PRL on NPY expression, and is most likely exacerbated by the physiological leptin resistance state.

Original languageEnglish
Pages (from-to)341-350
Number of pages10
JournalJournal of Endocrinology
Volume195
Issue number2
DOIs
StatePublished - Nov 2007

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