Mating Induces Switch From Hormone-Dependent to - Independent Steroid Receptor-Mediated Growth in Drosophila Prostate-Like Cells
Mating Induces Switch From Hormone-Dependent to - Independent Steroid Receptor-Mediated Growth in Drosophila Prostate-Like Cells
复制标题
交配诱导果蝇前列腺样细胞从激素依赖性生长转变为非类固醇受体介导的生长
DOI：
10.1101/533976
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Leiblich A
中科院分区：
文献类型：
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作者：
Leiblich A
雄性生殖腺，如哺乳动物的前列腺和成对的黑腹果蝇的副腺，分泌精液成分，提高繁殖力。在人类中，在环境调节的内分泌和局部雄激素的刺激下，前列腺在整个成年期都在生长。我们之前的研究表明，在每个苍蝇的副腺中，次生细胞（SCs）及其细胞核也在成虫体内生长，这一过程通过交配增强，并由骨形态发生蛋白（BMP）信号传导控制。在这里，我们证明了bmp介导的SC生长依赖于发育类固醇，蜕皮激素的受体，其浓度反映了成人的社会性经验。BMP信号在转录后部分通过EcR的n端调控蜕皮激素受体（EcR）的水平。处女雄性的核生长依赖于蜕皮激素。然而，交配激活基因组内复制，通过细胞类型特异性形式的激素非依赖性EcR信号，驱动额外的bmp介导的核生长。在蜕皮激素水平较低的处女中，这种机制确保了资源的保存。然而，通过在交配后切换到激素不依赖型，这种控制被推翻以过度激活分泌次生细胞的生长。我们的数据表明，这种生理、行为诱导的开关与前列腺癌进展相关的病理信号改变之间存在相似之处。
Male reproductive glands like the mammalian prostate and the pairedDrosophila melanogasteraccessory glands secrete seminal fluid components that enhance fecundity. In humans, the prostate grows throughout adult life, stimulated by environmentally regulated endocrine and local androgens. We previously showed that in each fly accessory gland, secondary cells (SCs) and their nuclei also grow in adults, a process enhanced by mating and controlled by bone morphogenetic protein (BMP) signalling. Here we demonstrate that BMP-mediated SC growth is dependent on the receptor for the developmental steroid, ecdysone, whose concentration reflects socio-sexual experience in adults. BMP signalling regulates ecdysone receptor (EcR) levels post-transcriptionally, partly via EcR’s N-terminus. Nuclear growth in virgin males is ecdysone-dependent. However, mating activates genome endoreplication to drive additional BMP-mediated nuclear growth via a cell type-specific form of hormone-independent EcR signalling. In virgin males with low ecdysone levels, this mechanism ensures resources are conserved. However, by switching to hormone-independence after mating, this control is overridden to hyper-activate growth of secretory secondary cells. Our data suggest parallels between this physiological, behaviour-induced switch and altered pathological signalling associated with prostate cancer progression.