Glucocorticoids and progesterone prevent apoptosis in the lactating rat mammary gland
Glucocorticoids and progesterone prevent apoptosis in the lactating rat mammary gland
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DOI：
10.1210/en.143.1.222
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发表时间：
2002-01-01
期刊：
影响因子：
4.8
通讯作者：
Waddell, BJ
中科院分区：
文献类型：
--
作者：
Berg, MN;Dharmarajan, AM;Waddell, BJ
细胞凋亡是一种非炎症性细胞死亡形式，在断奶后乳腺退化中发挥着核心作用。先前的研究表明，用糖皮质激素或黄体酮治疗可大大减少断奶后乳腺的细胞凋亡，但这些类固醇在正常哺乳期间是否发挥类似的抗细胞凋亡作用尚不清楚。因此，本研究使用体内大鼠模型来评估黄体酮和糖皮质激素对哺乳期乳腺细胞凋亡的影响。大鼠在哺乳期第 10 天未经治疗、进行假手术、卵巢切除 (OVX) 和/或肾上腺切除 (ADX)。其他组的 OVX/ADX 大鼠接受黄体酮或皮质酮治疗。 3天后，通过片段化DNA的3'末端标记和原位末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记分析(TUNEL)来测定乳腺细胞凋亡。未经治疗和假手术大鼠的乳腺中 DNA 碎片相对较低，且不受单独 ADX 或 OVX 的影响。相比之下，OVX/ADX 大鼠中的 DNA 碎片显着升高（P < 0.01），但通过用皮质酮或黄体酮替代可以防止这种对乳腺细胞凋亡的影响。与这些数据一致的是，在 OVX/ADX 大鼠乳腺组织的肺泡上皮中很容易观察到通过 TUNEL 分析鉴定出的死亡细胞，但在任何其他组中均未观察到。这些数据表明，在正常哺乳期间，乳腺细胞凋亡受到内源性黄体酮和糖皮质激素的抑制。重要的是，任何一种类固醇的单独存在都足以防止细胞凋亡，这表明它们在哺乳期乳腺中的抗细胞凋亡作用可能是通过类似的信号通路介导的。
Apoptosis, a form of noninflammatory cell death, plays a central role in mammary gland involution after weaning. Previous studies have shown that apoptosis in the post-weaning mammary gland is substantially reduced by treatment with glucocorticoids or progesterone, but whether these steroids exert a similar antiapoptotic effect during normal lactation is not known. Therefore, the present study used an in vivo rat model to assess the effects of progesterone and glucocorticoids on apoptosis in the lactating mammary gland. Rats were untreated, sham operated, ovariectomized (OVX), and/or adrenalectomized (ADX) on d 10 of lactation. Additional groups of OVX/ADX rats were treated with either progesterone or corticosterone. Mammary gland apoptosis was determined 3 d later by 3'-end labeling of fragmented DNA and by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling analysis (TUNEL). DNA fragmentation was relatively low in the mammary gland from untreated and sham-operated rats and was unaffected by either ADX or OVX alone. In contrast, DNA fragmentation was markedly elevated in OVX/ADX rats (P < 0.01), but this effect on mammary gland apoptosis was prevented by replacement with either corticosterone or progesterone. Consistent with these data, dying cells identified by TUNEL analysis were readily observed in the alveolar epithelium of mammary tissue from OVX/ADX rats but not in any of the other groups, These data demonstrate that during normal lactation, mammary gland apoptosis is inhibited by endogenous progesterone and glucocorticoids. Importantly, the presence of either steroid alone was sufficient to prevent apoptosis, suggesting that their antiapoptotic effects in the lactating mammary gland may be mediated via similar signaling pathways.