垂體（pituitary）是下丘腦-垂體-腎上腺 （HPA） 軸的重要樞紐。垂體激素分泌細胞 （HPC） 釋放多種激素，以在正常和壓力條件下調節基本身體功能。垂體內分泌腺通過釋放促腎上腺皮質激素 （ACTH） 來調節免疫系統，以響應下丘腦的神經元激活。然而，目前尚不清楚全身炎癥如何調節垂體HPC的轉錄組學特征。在這里，我們對小鼠垂體進行了單細胞RNA測序（scRNA-seq），發現在炎癥發生時，所有主要的垂體HPC都以細胞類型特異性方式產生強烈反應，其中皮質促物表現出強烈的(de)(de)反應(ying)。全(quan)身炎癥還導致非典型生物活性分子的(de)(de)產生和釋放(fang)，包括皮質激素的(de)(de) Nptx2，以調節(jie)免疫(yi)穩態(tai)。同時(shi)，HPCs上調了趨化因子的(de)(de)基因表達，促進了HPCs與免疫(yi)細胞(bao)之(zhi)間(jian)的(de)(de)通訊。總之(zhi)，我們的(de)(de)研究揭示了垂體(ti)和免疫(yi)系統(tong)之(zhi)間(jian)的(de)(de)廣泛(fan)相互作用(yong)，表明垂體(ti)在介導炎癥對身體(ti)生理學(xue)許多方面的(de)(de)影響方面發(fa)揮著多方面的(de)(de)作用(yong)。
Mice were anesthetized with pentobarbital (80 mg/kg, i.p.) before surgery and then placed in a mouse stereotaxic instrument. Injections were performed using a microsyringe pump and a Micro4 controller (World Precision Instruments). For macrophage depletion, liposome-PBS or liposome-Clodronate (Liposoma,CP-005-005) was stereotaxically microinjected into the anterior pituitary (2.5 mm posterior from Bregma, 0.4 mm lateral, 6 mm below pia). The liposomes were delivered to the target site at a rate of 60 nL/min for 500 nL per site. Mice received saline or 0.5 mg/kg LPS 18 h after liposome delivery and were killed 6 h after inflammation was established. For CCL2 expression and Nptx2-KO, AAV was delivered directly into the pituitary. The injection site, rate, and volume were the same as those used for the liposome injection. Subsequent experiments were performed at least 3 weeks after virus injection.
(C) Representative images showing Iba1 (the marker of macrophage) expression in the pituitary from mice that received liposome-PBS (left) or liposome-Clodronate (right) directly to the pituitary for 24 h. Scale bar, 100 μm.
(D) Serum concentrations of ACTH in saline- or LPS-treated (0.5 mg/kg LPS for 6 h) mice pretreated with liposome-PBS or liposome-Clodronate (n = 4–7 mice).
(E) Serum concentrations of corticosterone in LPS-treated (0.5 mg/kg LPS for 6 h) mice pretreated with liposome-PBS or liposome-Clodronate (n = 6–7 mice).
