STAT5 signaling in kisspeptin cells regulates the timing of puberty.
Previous studies have shown that kisspeptin neurons are important mediators of prolactin's effects on reproduction. However, the cellular mechanisms recruited by prolactin to affect kisspeptin neurons remain unknown. Using whole-cell patch-clamp recordings of brain slices from kisspeptin reporter mice, we observed that 20% of kisspeptin neurons in the anteroventral periventricular nucleus was indirectly depolarized by prolactin via an unknown population of prolactin responsive neurons. This effect required the phosphatidylinositol 3-kinase signaling pathway. No effects on the activity of arcuate kisspeptin neurons were observed, despite a high percentage (70%) of arcuate neurons expressing prolactin-induced STAT5 phosphorylation. To determine whether STAT5 expression in kisspeptin cells regulates reproduction, mice carrying Stat5a/b inactivation specifically in kisspeptin cells were generated. These mutants exhibited an early onset of estrous cyclicity, indicating that STAT5 transcription factors exert an inhibitory effect on the timing of puberty.
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Marina Augusto
MA
Silveira
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Isadora C
IC
Furigo
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Thais T
TT
Zampieri
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Tabata M
TM
Bohlen
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Daniella G
DG
de Paula
Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Celso Rodrigues
CR
Franci
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Jose
J
Donato
Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address: rfrazao@usp.br.
Renata
R
Frazao
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology; D015415:Biomarkers / Q000378:metabolism; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D007032:Hypothalamus, Anterior / Q000166:cytology; D059648:Kisspeptins / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011388:Prolactin / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D012741:Sexual Maturation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D015415:Biomarkers; D059648:Kisspeptins; D050799:STAT5 Transcription Factor; D011388:Prolactin; D019869:Phosphatidylinositol 3-Kinases
HPG axis; Hypothalamus; Kiss1; Prolactin; Sexual maturation; Whole-cell patch-clamp