Evans A C, Fortune J E
Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Endocrinology. 1997 Jul;138(7):2963-71. doi: 10.1210/endo.138.7.5245.
Mechanisms that allow selection of a dominant ovarian follicle from a cohort of growing follicles are unknown. Large healthy, estrogen-active follicles contain more LH receptors than atretic estrogen-inactive follicles, and levels of messenger RNA (mRNA) for LH receptor increase in the granulosa cells of dominant follicles as growth progresses. The aim of the present study was to test the hypothesis that changes in the temporal pattern of expression of mRNA for LH and FSH receptors are associated with selection of dominant follicles in cattle. Based on size, the dominant and two largest subordinate follicles were collected from the ovaries of heifers on days 2 (n = 3) or 3 (n = 3) of a follicular wave. On day 2, the dominant follicle was 1 mm larger than the largest subordinate follicle, but by day 3 of the wave the dominant follicle was 2-4 mm larger than the largest subordinate. Follicular fluid concentrations of estradiol and estradiol secretion in vitro by pieces of follicle wall (granulosa and theca cells) were greatest by the dominant compared with the subordinate follicles (P < 0.05). These data indicate that selection of a dominant follicle had occurred by the second day of the follicular wave. By in situ hybridization, mRNAs for LH and FSH receptors, P450 aromatase and P450 17alpha-hydroxylase (17alpha-OH) were localized in frozen sections from each follicle. The expression of mRNA for LH receptor in granulosa cells was always at or near background and was not different between days or follicle types (P = 0.63). In contrast, the expression of mRNA for LH receptor in theca cells of the same sections was readily detectable; there was no difference between follicle types on the second day of the follicular wave, but by the third day expression in the subordinate follicles had decreased (P < 0.05). The expression of mRNA for FSH receptor was highest in granulosa cells of dominant follicles collected on day 3 of the follicular wave (P < 0.05) and was not different between dominant and subordinate follicles on day 2 of the wave (P > 0.05). The expression of mRNA for aromatase in granulosa cells was similar (P > 0.05) between the dominant follicles on days 2 and 3 and the largest subordinate follicle on day 2 of the follicular wave and was much lower in the remaining follicles (P < 0.01). On day 2 of the wave, the expression of mRNA for 17alpha-OH was not different between the dominant and subordinate follicles, but by day 3 the dominant follicles had more mRNA for 17alpha-OH than the subordinate follicles (P < 0.05). These data show that the dominant follicle had been selected by the second day of the follicular wave (based on diameter and estradiol secretion) and that selection occurred in the absence of detectable levels of mRNA for LH receptor in the granulosa cells or differences between dominant and subordinate follicles in mRNA for LH receptor in theca cells or FSH receptor in granulosa cells. However, the divergent pattern of growth between dominant and subordinate follicles (after follicle selection) was associated with higher levels of mRNA for gonadotropin receptors and steroidogenic enzymes in dominant compared with subordinate follicles. Therefore, selection of the dominant follicle in cattle does not appear to involve the regulation of expression of mRNA for gonadotropin receptors, although such regulation may be important at other stages of differentiation of the dominant follicle.
从一群生长中的卵泡中选择优势卵泡的机制尚不清楚。健康的、具有雌激素活性的大卵泡比闭锁的、无雌激素活性的卵泡含有更多的促黄体生成素(LH)受体,并且随着优势卵泡的生长,其颗粒细胞中LH受体的信使核糖核酸(mRNA)水平会升高。本研究的目的是检验以下假设:LH和促卵泡素(FSH)受体mRNA表达的时间模式变化与牛优势卵泡的选择有关。根据大小,在卵泡波的第2天(n = 3)或第3天(n = 3)从后备母牛的卵巢中收集优势卵泡和两个最大的次级卵泡。在第2天,优势卵泡比最大的次级卵泡大1毫米,但到卵泡波的第3天,优势卵泡比最大的次级卵泡大2 - 4毫米。与次级卵泡相比,优势卵泡的卵泡液中雌二醇浓度以及卵泡壁(颗粒细胞和卵泡膜细胞)体外分泌的雌二醇量最大(P < 0.05)。这些数据表明,在卵泡波的第二天就已经发生了优势卵泡的选择。通过原位杂交,LH和FSH受体、细胞色素P450芳香化酶和细胞色素P450 17α - 羟化酶(17α - OH)的mRNA定位在每个卵泡的冰冻切片中。颗粒细胞中LH受体mRNA的表达始终处于或接近背景水平,在不同天数或卵泡类型之间没有差异(P = 0.63)。相反,同一切片中卵泡膜细胞中LH受体mRNA的表达很容易检测到;在卵泡波的第二天,不同卵泡类型之间没有差异,但到第三天,次级卵泡中的表达下降(P < 0.05)。FSH受体mRNA的表达在卵泡波第3天收集的优势卵泡的颗粒细胞中最高(P < 0.05),在卵泡波第2天,优势卵泡和次级卵泡之间没有差异(P > 0.05)。颗粒细胞中芳香化酶mRNA的表达在卵泡波第2天和第3天的优势卵泡以及第2天最大的次级卵泡之间相似(P > 0.05),在其余卵泡中则低得多(P < 0.01)。在卵泡波的第2天,优势卵泡和次级卵泡中17α - OH的mRNA表达没有差异,但到第3天,优势卵泡中17α - OH的mRNA比次级卵泡多(P < 0.05)。这些数据表明,在卵泡波的第二天(基于直径和雌二醇分泌)就已经选择了优势卵泡,并且这种选择发生在颗粒细胞中LH受体mRNA检测不到水平,或者优势卵泡和次级卵泡在卵泡膜细胞中LH受体mRNA或颗粒细胞中FSH受体mRNA没有差异的情况下。然而,优势卵泡和次级卵泡之间(卵泡选择后)不同的生长模式与优势卵泡中促性腺激素受体和类固醇生成酶的mRNA水平高于次级卵泡有关。因此,牛优势卵泡的选择似乎不涉及促性腺激素受体mRNA表达的调节,尽管这种调节在优势卵泡分化的其他阶段可能很重要。