Hormonal Regulation of Prolactin Cell Development in the Fetal Pituitary Gland of the Mouse
Hormonal Regulation of Prolactin Cell Development in the Fetal Pituitary Gland of the Mouse
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DOI：
10.1210/en.2008-1151
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发表时间：
2009-02-01
期刊：
影响因子：
4.8
通讯作者：
Hisano, Setsuji
中科院分区：
文献类型：
--
作者：
Ogasawara, Kiyomoto;Nogami, Haruo;Hisano, Setsuji
本文研究了小鼠胎脑垂体催乳素（PRL）细胞的发育过程。虽然PRL细胞在完整胎儿的脑垂体中几乎检测不到，但用17 β-雌二醇（E-2）在体外处理诱导了大量PRL细胞，这些细胞的数量根据妊娠阶段而变化，在胚胎d 15时达到峰值。这种作用是特定于E-2，表皮生长因子，胰岛素，毛喉素未能诱导PRL细胞。虽然雌激素受体（ER）α和ER β在胎儿垂体中表达，但ER敲除模型的结果表明，只有ER α介导E-2对PRL细胞的作用。在ER α缺陷小鼠及其对照同窝仔中观察到少数PRL细胞，表明PRL细胞的表型测定不需要雌激素。出乎意料的是，在胚胎d 15后，E-2对体外PRL细胞诱导的作用减弱。目前的研究结果表明，胎儿PRL细胞暴露于糖皮质激素（GC）的结果在降低敏感性E-2。雌激素敏感性的下调GC的机制被发现不是下调ER水平，诱导膜联蛋白1，GC诱导的PRL分泌抑制剂，或减少PRL前体细胞凋亡的数量。GC的作用在2小时内出现，并且不需要从头蛋白质合成。GC可能通过一种新的机制参与了妊娠期垂体PRL的沉默机制。（内分泌学150：1061-1068，2009）
The developmental process of prolactin (PRL) cells in the fetal pituitary gland was studied in mice. Although PRL cells were hardly detectable in the pituitary gland of intact fetuses, a treatment with 17 beta-estradiol (E-2) in vitro induced a number of PRL cells that varied drastically in number depending on the stage of gestation with a peak at embryonic d 15. This effect was specific to E-2, with epidermal growth factor, insulin, and forskolin failing to induce PRL cells. Although both estrogen receptor (ER)alpha and ER beta were expressed in the fetal pituitary gland, the results from ER knockout models showed that only ER alpha mediates E-2 action on PRL cells. A few PRL cells were observed in ER alpha-deficient mice as well as in their control littermates, suggesting that estrogen is not required for the phenotype determination of PRL cells. Unexpectedly, the effect of E-2 on the induction of PRL cells in vitro was diminished after embryonic d 15. Present results suggest that the exposure of fetal PRL cells to glucocorticoids (GCs) results in a reduction of sensitivity to E-2. The mechanism underlying the down-regulation of estrogen sensitivity by GCs was found not to be down-regulation of ER levels, induction of annexin 1, a GC-inducible inhibitor of PRL secretion, or a decrease in the number of PRL precursors by apoptosis. The effect of GCs appeared within 2 h and did not require a de novo protein synthesis. GCs are considered to be involved in the mechanisms of silencing pituitary PRL in gestation possibly through a novel mechanism. (Endocrinology 150: 1061-1068, 2009)