title: Neuronal STAT5 signaling is required for maintaining lactation but not for postpartum maternal behaviors in mice.
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.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.
authors.forename: Daniella C
authors.initials: DC
authors.lastname: Buonfiglio
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Ramos-Lobo
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Silveira
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil.
authors.forename: Isadora C
authors.initials: IC
authors.lastname: Furigo
authors.affiliation: Laboratory of Genetics and Physiology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lothar
authors.initials: L
authors.lastname: Hennighausen
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Frazão
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil. Electronic address: jdonato@icb.usp.br.
authors.forename: Jose
authors.initials: J
authors.lastname: Donato
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D005260:Female; D015870:Gene Expression / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D008297:Male; D008425:Maternal Behavior / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D049590:Postpartum Period / Q000523:psychology*; D011301:Preoptic Area / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D050799:STAT5 Transcription Factor; D011388:Prolactin
keywords: Hypothalamus; Preoptic region; Prolactin; Signaling pathways