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Article
| Open Access
Dicer ablation in Kiss1 neurons impairs puberty and fertility preferentially in female mice
Kiss1 neurons are essential for puberty and fertility. Here, the authors show that canonical microRNA biosynthesis in Kiss1 neurons plays an essential role in the control of puberty and fertility, especially in females, likely via repression of repressors on the Kiss1 gene.
- Juan Roa
- , Miguel Ruiz-Cruz
- & Manuel Tena-Sempere
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Article
| Open Access
Activating mutations in BRAF disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mice and humans
Mutations in components of the MAP kinase pathway are associated with a group of syndromes known as RASopathies. Here, the authors identify gain-of-function mutations in BRAF in patients with RASopathies and congenital hypopituitarisms. This article demonstrates a central role for BRAF in the development of the hypothalamo-pituitary axis leading to endocrine deficiencies in patients with RASopathies.
- Angelica Gualtieri
- , Nikolina Kyprianou
- & Carles Gaston-Massuet
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Article
| Open Access
Aberrant methylation underlies insulin gene expression in human insulinoma
Insulinomas are rare, benign beta cell tumours which overproduce insulin and have been associated to epigenetic alterations. Here the authors characterise insulinoma methylomes, finding changes in promoter methylation and chromatin structure proposed to drive the pathological expression of insulin.
- Esra Karakose
- , Huan Wang
- & Luca Lambertini
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Article
| Open Access
The circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders
Antenatal glucocorticoid therapy is indicated for mothers at risk of preterm delivery. Here, the authors show that the circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders later in life in mice and in a retrospective observational study in human infants.
- Mariana Astiz
- , Isabel Heyde
- & Henrik Oster
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Article
| Open Access
SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression
The onset of mammalian puberty is sensitive to metabolic changes and nutritional status, but the mechanisms underlying this phenomenon are poorly understood. Here the authors show that the epigenetic regulator of transcription, SIRT1, mediates the effects of under and overnutrition on pubertal timing by controlling the expression of Kiss1 in hypothalamic neurons.
- M. J. Vazquez
- , C. A. Toro
- & M. Tena-Sempere
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Article
| Open Access
p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1
Emerging studies suggest that p53 is an important regulator of energy metabolism, yet there is little known about the metabolic function of this tumor suppressor in the hypothalamus. Here, authors illustrate that p53, specifically in AgRP neurons, is required for adaptation to diet-induced obesity.
- Mar Quiñones
- , Omar Al-Massadi
- & Ruben Nogueiras
Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner