Justice Nicholas J, Blount Amy L, Pelosi Emanuele, Schlessinger David, Vale Wylie, Bilezikjian Louise M
Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Mol Endocrinol. 2011 Aug;25(8):1404-15. doi: 10.1210/me.2011-0093. Epub 2011 Jun 23.
Forkhead box L2 (FoxL2) is required for ovarian development and differentiation. FoxL2 is also expressed in the pituitary where it has been implicated in the development and regulation of gonadotropes, which secrete LH and FSH, the endocrine signals that regulate folliculogenesis in the ovary and spermatogenesis in the testis. Here, we show that FoxL2 is not required for the specification of gonadotropes; the pituitaries of Foxl2 mutant mice contain normal numbers of gonadotropes that express glycoprotein α subunit and LHβ. Whereas the specification of gonadotropes and all other hormonal cell types is normal in the pituitaries of Foxl2 mutant animals, FSHβ levels are severely impaired in both male and female animals, suggesting that FoxL2 is required for normal Fshb expression. The size of the pituitary is reduced in proportion to the smaller body size of Foxl2 mutants, with a concomitant increase in the pituitary cellular density. In primary pituitary cultures, activin induces FSH secretion and Fshb mRNA expression in cells from wild-type mice. In cells from Foxl2 mutant mice, however, FSH secretion is not detected, and activin is unable to drive Fshb expression, suggesting that the mechanism of activin-dependent activation of Fshb transcription is impaired. However, a small number of gonadotropes in the ventromedial region of the pituitaries from Foxl2 mutant mice maintain FSHβ expression, suggesting that a FoxL2- and activin-independent mechanism can drive Fshb transcription. These data indicate that, in addition to its role in the ovary, FoxL2 function in the pituitary is required for normal expression of FSH.
叉头框L2（FoxL2）是卵巢发育和分化所必需的。FoxL2也在垂体中表达，它与促性腺激素细胞的发育和调节有关，促性腺激素细胞分泌促黄体生成素（LH）和促卵泡生成素（FSH），这两种内分泌信号调节卵巢中的卵泡生成和睾丸中的精子发生。在此，我们表明FoxL2不是促性腺激素细胞特化所必需的；Foxl2突变小鼠的垂体中促性腺激素细胞数量正常，这些细胞表达糖蛋白α亚基和LHβ。虽然Foxl2突变动物垂体中促性腺激素细胞和所有其他激素细胞类型的特化是正常的，但雄性和雌性动物的FSHβ水平均严重受损，这表明FoxL2是正常Fshb表达所必需的。垂体的大小与Foxl2突变体较小的体型成比例减小，同时垂体细胞密度增加。在原代垂体培养中，激活素诱导野生型小鼠细胞分泌FSH并表达Fshb mRNA。然而，在Foxl2突变小鼠的细胞中，未检测到FSH分泌，激活素也无法驱动Fshb表达，这表明激活素依赖的Fshb转录激活机制受损。然而，Foxl2突变小鼠垂体腹内侧区域的少数促性腺激素细胞维持FSHβ表达，这表明一种不依赖FoxL2和激活素的机制可以驱动Fshb转录。这些数据表明，除了在卵巢中的作用外，垂体中FoxL2的功能对于FSH的正常表达也是必需的。
