Growth hormone receptor contributes to the activation of STAT5 in the hypothalamus of pregnant mice.
Growth hormone receptor contributes to the activation of STAT5 in the hypothalamus of pregnant mice.
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DOI：
10.1016/j.neulet.2021.136402
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发表时间：
2022-01-23
影响因子：
2.5
通讯作者：
Donato J Jr
中科院分区：
文献类型：
--
作者：
Wasinski F;Teixeira PDS;List EO;Kopchick JJ;Donato J Jr
生长激素（GH）受体（GHR）信号传导诱导包括下丘脑在内的几种组织细胞中的信号转导子和转录激活子5（pSTAT 5）的磷酸化。在怀孕期间，几种STAT 5募集激素（例如，催乳素、GH和胎盘催乳素）高度分泌。然而，目前尚不清楚GHR信号对妊娠小鼠下丘脑中发生的pSTAT 5免疫反应性神经元激增的确切贡献。因此，本研究的目的是确定是否GHR在神经元中的表达是必需的诱导pSTAT 5在几个下丘脑核在怀孕期间的表达。最初，我们证明，晚期妊娠的C57 BL/6小鼠（妊娠第14至18天）表现出增加脉冲GH分泌相比，处女雌性。接下来，我们证实神经元特异性GHR消融可大幅降低下丘脑Ghr mRNA水平，并阻止下丘脑弓状核、室旁核和腹内侧核中GH诱导的pSTAT 5。随后，在晚孕小鼠的下丘脑中测定pSTAT 5免疫反应性细胞的数量。虽然神经元特异性GHR消融不影响下丘脑室旁核中pSTAT 5免疫反应性细胞的数量，但与对照妊娠小鼠相比，在妊娠神经元特异性GHR敲除小鼠的弓状核和腹内侧核中观察到pSTAT 5表达减少。总之，下丘脑神经元的一个子集需要GHR信号在怀孕期间表达pSTAT 5。这些发现有助于了解影响怀孕期间大脑中转录因子激活的内分泌因素。
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 hypothalamic 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 hypothalamus, 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 understanding of the endocrine factors that affect the activation of transcription factors in the brain during pregnancy.
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