Pituitary Gonadotrophic Hormone Synthesis, Secretion, Subunit Gene Expression and Cell Structure in Normal and Follicle-Stimulating Hormone β Knockout, Follicle-Stimulating Hormone Receptor Knockout, Luteinising Hormone Receptor Knockout, Hypogonadal and Ovariectomised Female Mice
Pituitary Gonadotrophic Hormone Synthesis, Secretion, Subunit Gene Expression and Cell Structure in Normal and Follicle-Stimulating Hormone β Knockout, Follicle-Stimulating Hormone Receptor Knockout, Luteinising Hormone Receptor Knockout, Hypogonadal and Ovariectomised Female Mice
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DOI：
10.1111/jne.12178
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发表时间：
2014-11-01
影响因子：
3.2
通讯作者：
Christian, H. C.
中科院分区：
文献类型：
--
作者：
Abel, M. H.;Widen, A.;Christian, H. C.
为了研究促性腺激素功能和超微结构之间的关系，我们在雌性小鼠中平行比较了几种不同突变对下丘脑-垂体-性腺轴的影响。具体而言，血清和垂体促性腺激素浓度，促性腺激素基因表达，促性腺激素结构和数量进行了测量。将促卵泡激素敲除（FSHKO）、促卵泡激素受体敲除（FSHRKO）、促黄体生成激素受体敲除（LuRKO）、性腺功能减退（hpg）和卵巢切除小鼠与对照野生型或杂合子雌性小鼠进行比较。与杂合子雌性相比，FSHKO和FSHRKO中血清LH水平升高，反映KO雌性雌激素产生可能减少，正如线状子宫和无周期性所证明的那样。正如预期的那样，在FSHKO小鼠的血清或垂体中没有检测到FSH，并且FSH亚基基因不表达。然而，在FSHRKO雌性小鼠中FSH和LH亚基基因的表达显著增加。FSHKO和FSHRKO促性腺激素细胞的形态与对照组无显著差异，但FSHRKO促性腺激素细胞的分泌颗粒直径较大。在LuRKO和卵巢切除小鼠中，LH和FSH mRNA的刺激以及血清蛋白浓度反映在促性腺激素细胞形态的亚细胞变化中，包括更多扩张的粗面内质网和更少，更大的分泌颗粒。在促性腺激素释放激素缺乏的hpg小鼠，促性腺激素的mRNA和蛋白质水平显着低于对照组小鼠和促性腺激素细胞相应较小，丰富的内质网和分泌颗粒的数量减少。总之，在对照组和突变组雌性小鼠之间发现垂体含量和促性腺激素LH和FSH的血清浓度存在重大差异。这些变化与促性腺激素亚单位基因表达的变化有关，并反映在促性腺激素细胞内的细胞结构和分泌颗粒外观上。
To investigate the relationship between gonadotroph function and ultrastructure, we have compared, in parallel in female mice, the effects of several different mutations that perturb the hypothalamic-pituitary-gonadal axis. Specifically, serum and pituitary gonadotrophin concentrations, gonadotrophin gene expression, gonadotroph structure and number were measured. Follicle-stimulating hormone knockout (FSHKO), follicle-stimulating hormone receptor knockout (FSHRKO), luteinising hormone receptor knockout (LuRKO), hypogonadal (hpg) and ovariectomised mice were compared with control wild-type or heterozygote female mice. Serum levels of LH were elevated in FSHKO and FSHRKO compared to heterozygote females, reflecting the likely decreased oestrogen production in KO females, as demonstrated by the threadlike uteri and acyclicity. As expected, there was no detectable FSH in the serum or pituitary and an absence of expression of the FSH subunit gene in FSHKO mice. However, there was a significant increase in expression of the FSH and LH subunit genes in FSHRKO female mice. The morphology of FSHKO and FSHRKO gonadotrophs was not significantly different from the control, except that secretory granules in FSHRKO gonadotrophs were larger in diameter. In LuRKO and ovariectomised mice, stimulation of LH and FSH mRNA, as well as serum protein concentrations, were reflected in subcellular changes in gonadotroph morphology, including more dilated rough endoplasmic reticula and fewer, larger secretory granules. In the gonadotophin-releasing hormone deficient hpg mouse, gonadotrophin mRNA and protein levels were significantly lower than in control mice and gonadotrophs were correspondingly smaller with less abundant endoplasmic reticula and reduced numbers of secretory granules. In summary, major differences in pituitary content and serum concentrations of the gonadotrophins LH and FSH were found between control and mutant female mice. These changes were associated with changes in expression of the gonadotrophin subunit genes and were reflected in the cellular structure and secretory granule appearance within the gonadotroph cells.