DECIDUAL-TYPE PROLACTIN EXPRESSION BY THE HUMAN MYOMETRIUM

DECIDUAL-TYPE PROLACTIN EXPRESSION BY THE HUMAN MYOMETRIUM
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DOI:
10.1210/endo-129-1-158
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发表时间:
1991-07-01
期刊:
影响因子:
4.8
通讯作者:
BOHNET, HG
BOHNET, HG
中科院分区:
医学2区
文献类型:
--
作者:
GELLERSEN, B;BONHOFF, A;BOHNET, HG

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人子宫肌层,除了黄体晚期和妊娠期的蜕膜化子宫内膜外,已被提出作为子宫PRL的第二来源,因为在子宫肌层外植体培养物的上清液中发现了免疫反应性PRL。 我们在这里证明:1)人(h)PRL基因在体内子宫肌层中表达; 2)子宫肌层PRL与垂体hPRL相同; 3)编码转录物与垂体hPRL信使(m)RNA不同,但与蜕膜和IM-9-P3淋巴hPRL mRNA同源; 4)子宫肌层hPRL mRNA的表达被孕酮抑制。 用北方印迹杂交法在新鲜分离的子宫肌层中检测到hPRL mRNA,其大于垂体信使。 序列和引物延伸分析显示,该转录本与垂体帽位点下游的垂体hPRL mRNA相同,并携带与蜕膜/IM-9-P3淋巴hPRL mRNA同源的5 '非翻译区的延伸。 这种mRNA种类是由选择性转录起始引起的,包含hPRL基因的外显子1a,该基因在垂体中不转录。 hPRL mRNA稳态水平和hPRL分泌显着增加时,子宫肌层外植体保持在长期培养。 除了23,000 mol wt形式外,子宫肌层外植体还合成了糖基化hPRL变体(G-hPRL),其比垂体G-hPRL大约500道尔顿,但与淋巴G-hPRL大小相似(26,500)。 在Nb 2淋巴瘤生物测定中,子宫肌层条件培养基的泌乳活性与垂体hPRL的泌乳活性相同,并且通过加入hPRL的单克隆抗体来中和。 hPRL分泌和hPRL mRNA丰度不受雌激素的影响,但醋酸甲羟孕酮可显著降低hPRL分泌和hPRL mRNA丰度,醋酸甲羟孕酮在低至10(-10)M的剂量下最有效。
The human myometrium, in addition to the decidualized endometrium of the late luteal phase and of pregnancy, has been proposed as a second source of uterine PRL, since immunoreactive PRL was found in supernatants from myometrial explant cultures. We demonstrate here that: 1) the human (h) PRL gene is expressed in the myometrium in vivo; 2) myometrial PRL is identical to pituitary hPRL; 3) the encoding transcript differs from pituitary hPRL messenger (m) RNA but is homologous to decidual and IM-9-P3 lymphoid hPRL mRNA; and 4) the expression of myometrial hPRL mRNA is inhibited by progestin. hPRL mRNA was detected in freshly isolated myometrium by Northern blot hybridization and was larger than the pituitary message. Sequence and primer extension analyses revealed that the transcript is identical to pituitary hPRL mRNA downstream of the pituitary cap site and carries an extension of the 5'-untranslated region homologous to that of decidual/IM-9-P3 lymphoid hPRL mRNA. This mRNA species results from alternative transcription initiation and comprises exon 1a of the hPRL gene, which is not transcribed in the pituitary. hPRL mRNA steady state levels and hPRL secretion increased dramatically when myometrial explants were maintained in long term culture. In addition to the 23,000 mol wt form, myometrial explants synthesized a glycosylated hPRL variant (G-hPRL) which was approximately 500 Daltons larger than pituitary G-hPRL but of similar size as lymphoid G-hPRL (26,500). Lactogenic activity of myometrial conditioned medium paralleled that of pituitary hPRL in the Nb2 lymphoma bioassay and was neutralized by the addition of monoclonal antibody to hPRL. hPRL secretion and hPRL mRNA abundance were not affected by estrogen but were markedly reduced by medroxy-progesterone acetate, which was maximally effective at a dose as low as 10(-10) M.