Neuronal STAT5 signaling is required for maintaining lactation but not for postpartum maternal behaviors in mice

Author(s)

Buonfiglio, Daniella C. ^[1] ; Ramos-Lobo, Angela M. ^[1] ; Silveira, Marina A. ^[2] ; Furigo, Isadora C. ^[1] ; Hennighausen, Lothar ^[3] ; Frazao, Renata ^[2] ; Donato, Jr., Jose ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Anat, Inst Biomed Sci, BR-05508900 Sao Paulo, SP - Brazil

^[3] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 - USA

• Document type: Journal article
• Source: Hormones and Behavior; v. 71, p. 60-68, MAY 2015.
• Web of Science Citations: 12

Abstract

Prolactin and placental lactogens control mammary development and lactation as well as play an important role in maternal behaviors. However, the molecular mechanisms in the brain responsible for this regulation remain largely unknown. Therefore, the present study investigated whether Signal Transducer and Activator of Transcription 5 (STAT5) signaling in the brain, the key transcriptional factor recruited by prolactin receptor and other hormones, is required for postpartum maternal behavior, maintenance of lactation and offspring growth. Neuronal ablation of STAT5 impaired the control of prolactin secretion and reduced the hypothalamic expression of suppressors of cytokine signaling (i.e., SOCS3 and CISH). In addition, neuronal STAT5 deletion attenuated the hyperphagia commonly observed during lactation by decreasing the hypothalamic expression of orexigenic neurotransmitters such as the neuropeptide Y and agouti-related protein. The lower food intake of lactating neuron-specific STAT5 knockout females resulted in reduced milk production and offspring growth. Unexpectedly, postpartum maternal behavior expression was not impaired in neuron-specific STAT5 knockout females. On the contrary, the latency to retrieve and group the pups into the nest was reduced in mutant dams. Finally, we demonstrated that approximately 30% of recorded neurons in the medial preoptic area were acutely depolarized by prolactin suggesting that fast STAT5-independent signaling pathways may be involved in the regulation of maternal behaviors. Overall, our results revealed important information about the molecular mechanisms recruited by hormones to orchestrate the activation of neural circuitries engaged in the induction of maternal care. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 12/12202-4 - Kiss1 neurons biophysical properties modulation by circadian factors
• Grantee: Renata Frazão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/21722-4 - Mechanism of action of bromocriptine and prolactin antagonists in the treatment of Diabetes and Obesity
• Grantee: Isadora Clivatti Furigo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/11752-6 - Study of leptin functions during intrauterine and childhood stages in mice
• Grantee: Angela Maria Ramos Lobo
• Support Opportunities: Scholarships in Brazil - Doctorate