Jih M H, Lu J K, Wan Y J, Wu T C
Department of Obstetrics and Gynecology, University of California School of Medicine, Los Angeles 90024.
Endocrinology. 1993 Jan;132(1):319-26. doi: 10.1210/endo.132.1.8419130.
In young adult female rats, the patterns of inhibin subunit mRNA expression during the estrous cycle are regulated by cyclic changes in gonadotropin secretion and follicular development. Since there are distinct alterations in profiles of both hormone secretion and folliculogenesis during the reproductive lifespan of the female rat, we have characterized the gene expression and distribution of inhibin subunit mRNAs in immature (22 days), young adult cyclic (3-4 months), middle-aged cyclic (9-10 months), and old (12-13 months) persistent estrous (PE) rat ovaries. Northern blot analyses revealed that in contrast to young adult cyclic rats, inhibin alpha- and beta A-subunit mRNA levels in the ovaries of middle-aged cyclic rats remained substantially elevated after the proestrous gonadotropin surges and ovulation. Likewise, acyclic immature and old PE rats showed high levels of inhibin alpha- and beta A-subunit transcripts in their ovaries. In situ hybridization analyses demonstrated that inhibin alpha- and beta A mRNAs were abundantly expressed in maturing follicles of both young and middle-aged cyclic females, while high levels of alpha-subunit transcripts were only detected in the ovarian stroma of middle-aged animals. The ovaries of old PE rats had numerous large cystic follicles (with variable layers of granulosa cells) and few degenerating cyst-like structures (completely devoid of granulosa cells). Inhibin subunit transcripts were expressed abundantly in both the granulosa (alpha and beta A-subunits) and theca interna (alpha-subunit only) layers of large follicles, but were absent from degenerating cysts devoid of granulosa cells. The ovarian stroma of PE rats also expressed very high levels of inhibin-alpha, but not beta A mRNA. The ovaries of immature rats contained large numbers of uniformly developing secondary follicles. High levels of inhibin-alpha mRNA were expressed homogeneously in the granulosa layer of all growing follicles, whereas inhibin beta A mRNAs were only detected in selectively larger follicles with multiple layers of granulosa cells. Hormone RIAs of serum samples from these same groups of animals showed that basal levels of serum FSH were substantially higher in immature, middle-aged cyclic, and old PE rats than in young adult rats. These results demonstrate that enhanced ovarian inhibin subunit gene expression in the female rat is associated with increased serum FSH levels regardless of chronological age. On the other hand, aging appears to selectively enhance inhibin alpha, but not beta A, gene expression in the ovarian stroma, such that it may gradually become a major secondary site of alpha-subunit mRNA production in addition to the follicular compartments.
在年轻成年雌性大鼠中，动情周期中抑制素亚基mRNA的表达模式受促性腺激素分泌和卵泡发育的周期性变化调节。由于雌性大鼠生殖寿命期间激素分泌和卵泡发生的概况有明显改变，我们已对未成熟（22日龄）、年轻成年动情周期（3 - 4月龄）、中年动情周期（9 - 10月龄）和老年（12 - 13月龄）持续性动情（PE）大鼠卵巢中抑制素亚基mRNA的基因表达和分布进行了表征。Northern印迹分析显示，与年轻成年动情周期大鼠相比，中年动情周期大鼠卵巢中抑制素α和βA亚基mRNA水平在动情前期促性腺激素高峰和排卵后仍显著升高。同样，无周期的未成熟和老年PE大鼠卵巢中也显示出高水平的抑制素α和βA亚基转录本。原位杂交分析表明，抑制素α和βA mRNA在年轻和中年动情周期雌性的成熟卵泡中大量表达，而仅在中年动物的卵巢基质中检测到高水平的α亚基转录本。老年PE大鼠的卵巢有许多大的囊性卵泡（颗粒细胞层数可变）和少数退化的囊肿样结构（完全没有颗粒细胞）。抑制素亚基转录本在大卵泡的颗粒层（α和βA亚基）和内膜层（仅α亚基）中大量表达，但在没有颗粒细胞的退化囊肿中不存在。PE大鼠的卵巢基质也表达非常高水平的抑制素α，但不表达βA mRNA。未成熟大鼠的卵巢含有大量均匀发育的次级卵泡。所有生长卵泡的颗粒层中均均匀表达高水平的抑制素α mRNA，而仅在有多层颗粒细胞的选择性较大卵泡中检测到抑制素βA mRNA。对这些相同组动物的血清样本进行激素放射免疫分析表明，未成熟、中年动情周期和老年PE大鼠血清FSH的基础水平显著高于年轻成年大鼠。这些结果表明，雌性大鼠卵巢抑制素亚基基因表达增强与血清FSH水平升高相关，与实际年龄无关。另一方面，衰老似乎选择性地增强卵巢基质中抑制素α而不是βA的基因表达，使得它除了卵泡区室之外可能逐渐成为α亚基mRNA产生的主要次要部位。
