STAT5 signaling in kisspeptin cells regulates the timing of puberty

Author(s)

Silveira, Marina Augusto ; Furigo, Isadora C. ; Zampieri, Thais T. ; Bohlen, Tabata M. ; de Paula, Daniella G. ; Franci, Celso Rodrigues ; Donato, Jr., Jose ; Frazao, Renata

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 448, n. C, p. 55-65, JUN 15 2017.
• Web of Science Citations: 13

Abstract

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. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 15/20198-5 - Role of Leptin in puberal neuromodulation
• Grantee: Thais Tessari Zampieri
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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: 15/10992-6 - Investigation of metabolic programming through different approaches
• Grantee: Jose Donato Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07908-8 - Precocious puberty in childhood obesity: possible mechanisms and influence of leptin
• 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: 15/14588-5 - Influence of leptin sensitivity in mice sexual maturation
• Grantee: Tabata Mariz Bohlen
• Support Opportunities: Scholarships in Brazil - Doctorate