The arcuate nucleus (ARH) is an important hypothalamic area for the homeostatic control of feeding and other metabolic functions. In the ARH, proopiomelanocortin- (POMC) and agouti-related peptide (AgRP)-expressing neurons play a key role in the central regulation of metabolism. These neurons are influenced by circulating factors, such as leptin and growth hormone (GH). The objective of the present study was to determine whether a direct action of GH on ARH neurons regulates the density of POMC and AgRP axonal projections to major postsynaptic targets. We studied POMC and AgRP axonal projections to the hypothalamic paraventricular (PVH), lateral (LHA) and dorsomedial (DMH) nuclei in leptin receptor (LepR)-deficient mice (Leprdb/db), GH-deficient mice (Ghrhrlit/lit) and in mice carrying specific ablations of GH receptor (GHR) either in LepR- or AgRP-expressing cells. Leprdb/db mice presented reduction in the density of POMC innervation to the PVH compared to wild-type and Ghrhrlit/lit mice. Additionally, both Leprdb/db and Ghrhrlit/lit mice showed reduced AgRP fiber density in the PVH, LHA and DMH. LepR GHR knockout mice showed decreased density of POMC innervation in the PVH and DMH, compared to control mice, whereas a reduction in the density of AgRP innervation was observed in all areas analyzed. Conversely, AgRP-specific ablation of GHR led to a significant reduction in AgRP projections to the PVH, LHA and DMH, without affecting POMC innervation. Our findings indicate that GH has direct trophic effects on the formation of POMC and AgRP axonal projections and provide additional evidence that GH regulates hypothalamic neurocircuits controlling energy homeostasis.

中文翻译：

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生长激素受体的缺失降低了下丘脑弓状弓形核神经元的轴突投射密度。

弓形核（ARH）是下丘脑的重要区域，可用于稳定控制进食和其他代谢功能。在ARH中，表达proopiomelanocortin-（POMC）和与刺豚鼠相关的肽（AgRP）的神经元在代谢的中央调节中起关键作用。这些神经元受到诸如瘦素和生长激素（GH）等循环因素的影响。本研究的目的是确定GH对ARH神经元的直接作用是否调节POMC和AgRP轴突向主要突触后靶标的密度。我们研究了瘦素受体（LepR）缺陷小鼠（Leprdb / db）对下丘脑室旁（PVH），外侧（LHA）和背体（DMH）核的POMC和AgRP轴突投射，GH缺陷小鼠（Ghrhrlit / lit）和在表达LepR或AgRP的细胞中携带GH受体（GHR）特异性切除的小鼠中。与野生型和Ghrhrlit / lit小鼠相比，Leprdb / db小鼠的POMC对PVH的神经支配密度降低。此外，Leprdb / db和Ghrhrlit / lit小鼠均显示PVH，LHA和DMH中的AgRP纤维密度降低。与对照小鼠相比，LepR GHR基因敲除小鼠显示PVH和DMH中POMC神经支配密度降低，而在所有分析区域中均观察到AgRP神经支配密度降低。相反，AgHR特异性的GHR消融导致AgRP对PVH，LHA和DMH的预测显着减少，而不会影响POMC的神经支配。