Growth hormone receptor contributes to the activation of STAT5 in the hypothalamus of pregnant mice

Autor(es)

Wasinski, Frederick ^[1] ; Teixeira, Pryscila D. S. ^[1] ; List, Edward O. ^{[2, 3]} ; Kopchick, John J. ^{[2, 3]} ; Donato Jr, Jose

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508000 Sao Paulo - Brazil

^[2] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 - USA

^[3] Ohio Univ, Heritage Coll Osteopath Med, Athens, OH 45701 - USA

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience Letters; v. 770, JAN 23 2022.
• Citações Web of Science: 0

Resumo

Growth hormone (GH) receptor (GHR) signaling induces the phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the cells of several tissues including in the hypothalamus. During pregnancy, several STAT5-recruiting hormones (e.g., prolactin, GH and placental lactogens) are highly secreted. However, the precise contribution of GHR signaling to the surge of pSTAT5 immunoreactive neurons that occurs in the hypothalamus of pregnant mice is currently unknown. Thus, the objective of the present study was to determine whether GHR expression in neurons is required for inducing pSTAT5 expression in several hypo-thalamic nuclei during pregnancy. Initially, we demonstrated that late pregnant C57BL/6 mice (gestational day 14 to 18) exhibited increased pulsatile GH secretion compared to virgin females. Next, we confirmed that neuron-specific GHR ablation robustly reduces hypothalamic Ghr mRNA levels and prevents GH-induced pSTAT5 in the arcuate, paraventricular and ventromedial hypothalamic nuclei. Subsequently, the number of pSTAT5 immunoreactive cells was determined in the hypothalamus of late pregnant mice. Although neuron-specific GHR ablation did not affect the number of pSTAT5 immunoreactive cells in the paraventricular nucleus of the hy-pothalamus, reduced pSTAT5 expression was observed in the arcuate and ventromedial nuclei of pregnant neuron-specific GHR knockouts, compared to control pregnant mice. In summary, a subset of hypothalamic neurons requires GHR signaling to express pSTAT5 during pregnancy. These findings contribute to the under-standing of the endocrine factors that affect the activation of transcription factors in the brain during pregnancy. (AU)

• Processo FAPESP: 20/01318-8 - Sistema nervoso central como um alvo do hormônio do crescimento para a regulação de múltiplas funções biológicas
• Beneficiário: Jose Donato Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/20897-3 - Papel dos neurônios orexina como mediadores dos efeitos centrais induzidos pelo hormônio do crescimento
• Beneficiário: Frederick Wasinski
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado