Department of Interdisciplinary Medicine, "Aldo Moro" University of Bari, Bari, Italy.
INBB, National Institute for Biostuctures and Biosystems, Rome, Italy.
Cell Mol Life Sci. 2019 Dec;76(24):5011-5025. doi: 10.1007/s00018-019-03160-y. Epub 2019 Jun 1.
The PPARγ coactivator 1α (PGC-1α) is a transcriptional regulator of mitochondrial biogenesis and oxidative metabolism. Recent studies have highlighted a fundamental role of PGC-1α in promoting breast cancer progression and metastasis, but the physiological role of this coactivator in the development of mammary glands is still unknown. First, we show that PGC-1α is highly expressed during puberty and involution, but nearly disappeared in pregnancy and lactation. Then, taking advantage of a newly generated transgenic mouse model with a stable and specific overexpression of PGC-1α in mammary glands, we demonstrate that the re-expression of this coactivator during the lactation stage leads to a precocious regression of the mammary glands. Thus, we propose that PGC-1α action is non-essential during pregnancy and lactation, whereas it is indispensable during involution. The rapid preadipocyte-adipocyte transition, together with an increased rate of apoptosis promotes a premature mammary glands involution that cause lactation defects and pup growth retardation. Overall, we provide new insights in the comprehension of female reproductive cycles and lactation deficiency, thus opening new roads for mothers that cannot breastfeed.
过氧化物酶体增殖物激活受体γ 共激活因子 1α（PGC-1α）是一种参与调控线粒体生物发生和氧化代谢的转录调节因子。最近的研究强调了 PGC-1α 在促进乳腺癌进展和转移方面的基本作用，但这种共激活因子在乳腺发育中的生理作用仍不清楚。首先，我们发现 PGC-1α 在青春期和退化期高度表达，但在怀孕和哺乳期几乎消失。然后，利用新生成的乳腺特异性过表达 PGC-1α 的转基因小鼠模型，我们证明在哺乳期重新表达这种共激活因子会导致乳腺提前退化。因此，我们提出 PGC-1α 在怀孕期间和哺乳期的作用不是必需的，而在退化期则是必不可少的。快速的前脂肪细胞-脂肪细胞转化，加上凋亡率的增加，促进了乳腺的过早退化，导致哺乳缺陷和幼崽生长迟缓。总的来说，我们为理解女性生殖周期和哺乳不足提供了新的见解，为无法母乳喂养的母亲开辟了新的道路。
