title: Possible crosstalk between leptin and prolactin during pregnancy.
abstract: Rodents exhibit leptin resistance and high levels of prolactin/placental lactogens during pregnancy. A crosstalk between prolactin and leptin signaling has been proposed as a possible mechanism to explain the changes in energy balance during gestation. However, it remains unclear if specific neuronal populations co-express leptin and prolactin receptors. Therefore, our present study was undertaken to identify in the mouse brain prolactin-responsive cells that possibly express the leptin receptor (LepR). In addition, we assessed the leptin response in different brain nuclei of pregnant and nulliparous mice. We used a LepR-reporter mouse to visualize LepR-expressing cells with the tdTomato fluorescent protein. Prolactin-responsive cells were visualized with the immunohistochemical detection of the phosphorylated form of the signal transducer and activator of transcription-5 (pSTAT5-ir). Notably, many neurons that co-expressed tdTomato and pSTAT5-ir were observed in the medial preoptic area (MPA, 27-48% of tdTomato cells), the retrochiasmatic area (34-51%) and the nucleus of the solitary tract (NTS, 16-24%) of prolactin-treated nulliparous mice, pregnant mice and prolactin-treated leptin-deficient (ob/ob) mice. The arcuate nucleus of the hypothalamus (8-22%), the medial tuberal nucleus (11-15%) and the ventral premammillary nucleus (4-10%) showed smaller percentages of double-labeled cells among the groups. Other brain nuclei did not show significant percentages of neurons that co-expressed tdTomato and pSTAT5-ir. Late pregnant mice exhibited a reduced leptin response in the MPA and NTS when compared with nulliparous mice; however, a normal leptin response was observed in other brain nuclei. In conclusion, our findings shed light on how the brain integrates the information conveyed by leptin and prolactin. Our results corroborate the hypothesis that high levels of prolactin or placental lactogens during pregnancy may directly interfere with LepR signaling, possibly predisposing to leptin resistance.
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors: V S
authors: VS
authors: Nagaishi
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors: L I
authors: LI
authors: Cardinali
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors: T T
authors: TT
authors: Zampieri
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors: I C
authors: IC
authors: Furigo
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors: M
authors: M
authors: Metzger
authors: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address: jdonato@icb.usp.br.
authors: J
authors: J
authors: Donato
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010298:Parity / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D020738:Leptin; D022661:RNA, Untranslated; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D011388:Prolactin
keywords: 0.02M potassium phosphate-buffered saline; 3,3′-diaminobenzidine; 3v; ANOVA; AP; ARH; AgRP; DAB; DMH; KPBS; LHA; LepR; MPA; MTu; NPY; NTS; OVLT; PBS; PMV; POMC; PVH; PrlR; RCA; SOCS; STAT3; STAT5; STATs; VMH; VMHdm; VMHvl; agouti-related peptide; analysis of variance; arcuate nucleus of the hypothalamus; area postrema; cc; central channel; cytokine receptor; dorsomedial nucleus of the hypothalamus; dorsomedial subdivision of the VMH; energy balance; f; fornix; gestation; hypothalamus; lateral hypothalamic area; leptin receptor; medial preoptic area; medial tuberal nucleus; neuropeptide Y; nucleus of the solitary tract; oc; optic chiasm; organum vasculosum of the lamina terminalis; pSTAT3; pSTAT3 immunoreactivity; pSTAT3-ir; pSTAT5; pSTAT5 immunoreactivity; pSTAT5-ir; paraventricular nucleus of the hypothalamus; phosphate-buffered saline; phosphorylated form of signal transducer and activator of transcription-3; phosphorylated form of signal transducer and activator of transcription-5; prolactin receptor; proopiomelanocortin; retrochiasmatic area; signal transducer and activators of transcription; suppressors of cytokine signaling; third ventricle; ventral premammillary nucleus; ventrolateral subdivision of the VMH; ventromedial nucleus of the hypothalamus