PDF(Pubmed)
Abstract：
Postnatal development of functional pituitary gonadotrophs is necessary for maturation of the hypothalamic-pituitary-gonadal axis, puberty, and reproduction. Here we examined the role of PI4-kinase A, which catalyzes the biosynthesis of PI4P in mouse reproduction by knocking out this enzyme in cells expressing the gonadotropin-releasing hormone (GnRH) receptor. Knockout (KO) mice were infertile, reflecting underdeveloped gonads and reproductive tracts and lack of puberty. The number and distribution of hypothalamic GnRH neurons and Gnrh1 expression in postnatal KOs were not affected, whereas Kiss1/kisspeptin expression was increased. KO of PI4-kinase A also did not alter embryonic establishment and neonatal development and function of the gonadotroph population. However, during the postnatal period, there was a progressive loss of expression of gonadotroph-specific genes, including Fshb, Lhb, and Gnrhr, accompanied by low gonadotropin synthesis. The postnatal gonadotroph population also progressively declined, reaching approximately one-third of that observed in controls at 3 months of age. In these residual gonadotrophs, GnRH-dependent calcium signaling and calcium-dependent membrane potential changes were lost, but intracellular administration of inositol-14,5-trisphosphate rescued this signaling. These results indicate a key role for PI4-kinase A in the postnatal development and maintenance of a functional gonadotroph population.
摘要：
功能性垂体促性腺激素的出生后发育是下丘脑-垂体-性腺轴成熟所必需的，青春期,和繁殖。在这里，我们检查了PI4激酶A的作用，催化PI4P的生物合成，通过在表达促性腺激素释放激素（GnRH）受体的细胞中敲除该酶，在小鼠繁殖中。敲除小鼠不育，反映性腺和生殖道发育不发达，缺乏青春期。敲除后下丘脑GnRH神经元的数量和分布及Gnrh1的表达均不受影响，而Kiss1/Kisspeptin表达增加。PI4激酶A的基因敲除也不会改变促性腺激素群体的胚胎建立和新生儿发育以及功能。然而,在产后期间，促性腺激素特异性基因的表达逐渐丧失，包括Fshb,Lhb,和Gnrhr,伴有低促性腺激素合成。出生后的促性腺激素种群也逐渐下降，达到3个月大时对照组观察到的约1/3。在这些残留的促性腺激素中，GnRH依赖性钙信号,钙依赖性膜电位变化消失了，但是肌醇-1,4,5-三磷酸的细胞内给药挽救了这种信号。这些结果表明PI4-激酶A在功能性促性腺激素群体的出生后发育和维持中的关键作用。
