Kageyama Kazunori, Murasawa Shingo, Niioka Kanako, Otsuka Fumio, Yagi Hiroko, Daimon Makoto
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan.
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan.
Neurosci Lett. 2017 Nov 1;660:63-67. doi: 10.1016/j.neulet.2017.08.052. Epub 2017 Aug 26.
A close interaction has been shown between the hypothalamo-pituitary-gonadal axis and the hypothalamic-pituitary-adrenal axis. Urocortin 2 (Ucn2) has a very high affinity for the corticotropin-releasing factor (CRF) type 2 (CRF) receptor. Pituitary Ucn2 regulates expression and secretion of gonadotropins in response to stress. The CRF receptor in the pituitary contributes to the modulation of gonadotropins. To explore the possible function of Ucn2 and the CRF receptor in pituitary gonadotropic tumor cells, we examined the direct regulation of gonadotropins by Ucn2 in a representative pituitary gonadotropic tumor, mouse LβT2 cells. LβT2 cells were found to express CRF receptor and CRF receptor mRNA. Ucn2 decreased CRF receptor mRNA levels, while it increased CRF receptor mRNA levels. Ucn2 directly decreased the mRNA levels of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in LβT2 cells. Ucn2 also decreased gonadotropin-releasing hormone receptor (GnRHR) mRNA levels. A selective CRF receptor antagonist suppressed the Ucn2-induced decreases in LH, FSH, and GnRHR mRNA levels. Ucn2 acts on gonadotrophs expressing the CRF receptor, and inhibits the production of gonadotropins in the pituitary gonadotropic tumor cells. (177 words).
下丘脑 - 垂体 - 性腺轴与下丘脑 - 垂体 - 肾上腺轴之间已显示出密切的相互作用。尿皮质素2（Ucn2）对促肾上腺皮质激素释放因子（CRF）2型（CRF2）受体具有非常高的亲和力。垂体Ucn2可响应应激调节促性腺激素的表达和分泌。垂体中的CRF受体有助于调节促性腺激素。为了探究Ucn2和CRF受体在垂体促性腺肿瘤细胞中的可能功能，我们在一种代表性的垂体促性腺肿瘤——小鼠LβT2细胞中检测了Ucn2对促性腺激素的直接调节作用。发现LβT2细胞表达CRF受体和CRF受体mRNA。Ucn2降低了CRF受体mRNA水平，同时又增加了CRF受体mRNA水平。Ucn2直接降低了LβT2细胞中促黄体生成素（LH）和促卵泡生成素（FSH）的mRNA水平。Ucn2还降低了促性腺激素释放激素受体（GnRHR）的mRNA水平。一种选择性CRF受体拮抗剂抑制了Ucn2诱导的LH、FSH和GnRHR mRNA水平的降低。Ucn2作用于表达CRF受体的促性腺细胞，并抑制垂体促性腺肿瘤细胞中促性腺激素的产生。
