Transcriptional and spatiotemporal regulation of prolactin receptor mRNA and cooperativity with progesterone receptor function during ductal branch growth in the mammary gland

Transcriptional and spatiotemporal regulation of prolactin receptor mRNA and cooperativity with progesterone receptor function during ductal branch growth in the mammary gland
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DOI:
10.1002/dvdy.1179
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发表时间:
2001-10-01
影响因子:
2.5
通讯作者:
Vonderhaar, BK
Vonderhaar, BK
中科院分区:
生物学3区
文献类型:
--
作者:
Hovey, RC;Trott, JF;Vonderhaar, BK

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乳腺内的导管分支由通过其受体(PRLR和PR)起作用的催乳素(PRL)和孕酮(P)刺激。乳腺PRLR表达的分析表明,增加表达的长型(L-PRLR)和两个三个短的形式(S1-和S3-PRLR)在青春期,成为最大的青春期后期和妊娠早期,然后在妊娠期间下降。相反,S2-PRLR mRNA水平保持恒定。间质PRLR的检查显示L-PRLR mRNA的一致表达。相比之下,S1-PRLR仅存在于新生儿的乳腺脂肪垫中,而新生儿S2-PRLR的高表达在青春期变得不可检测。S3-PRLR的基质表达在青春期下降到较低水平,在哺乳期和退化期检测不到。外源性催乳素在体内刺激上皮细胞和邻近基质细胞的DNA合成。催乳素受体mRNA在青春期前乳腺上皮中的分布是均匀的,而在青春期、妊娠期和泌乳早期是不均匀的。PRLR和PR的相互作用的建议,其中PR mRNA增加超过6周,在青春期和妊娠期达到最高水平,然后在哺乳期变得不可检测。原位杂交结果显示,孕6周前乳腺导管上皮中PRmRNA的分布是均匀的,而在青春期和妊娠期乳腺导管上皮中PRLR和PR的分布是不均匀的。这两种激素都不能刺激去卵巢雌性乳腺的DNA合成,但它们的作用相互作用显着。这些结果证明了上皮细胞和基质细胞的差异PRLR转录,以及a. PRLR和PR的相似分布可能促进乳腺导管分支期间P和PRL之间的相互作用。出版于2001年Wiley-Liss,Inc.
Ductal branching within the mammary gland is stimulated by prolactin (PRL) and progesterone (P) acting through their receptors (PRLR and PR). Analysis of mammary gland PRLR expression revealed increasing expression of the long form (L-PRLR) and two of the three short forms (S1- and S3-PRLR) during puberty that became maximal late in pubescence and early gestation, then declined during gestation. By contrast, S2-PRLR mRNA levels remained constant. Examination of stromal PRLR revealed the consistent expression of L-PRLR mRNA. By contrast, S1-PRLR was present only in the mammary fat pad of neonates, whereas high neonatal expression of S2-PRLR became undetectable during puberty. Stromal expression of S3-PRLR decreased to low levels during puberty and was undetectable during lactation and involution. Exogenous PRL stimulated DNA synthesis in both epithelial and adjacent stromal cells in vivo. Distribution of PRLR mRNA in mammary epithelium was homogeneous before puberty, and heterogeneous during puberty, gestation, and early lactation. A mutual role for PRLR and PR was suggested wherein PR mRNA increased beyond 6 weeks to maximal levels during puberty and gestation then became undetectable during lactation. In situ hybridization revealed that PR mRNA distribution is homogeneous in the ductal epithelium before 6 weeks and heterogenous during puberty and gestation and that PRLR and PR are similarly distributed in the ductal epithelium. Neither hormone stimulated DNA synthesis in mammary glands of ovariectomized females while their effects interacted markedly. These results demonstrate differential PRLR transcription by epithelial and stromal cells and a. similar distribution of PRLR and PR that may facilitate the interaction between P and PRL during ductal branching in the Mammary gland. Published 2001 Wiley-Liss, Inc.