One class of growth hormone (GH) receptor and binding protein messenger ribonucleic acid in rat liver, GHR1, is sexually dimorphic and regulated by GH.
One class of growth hormone (GH) receptor and binding protein messenger ribonucleic acid in rat liver, GHR1, is sexually dimorphic and regulated by GH.
复制标题
大鼠肝脏中的一类生长激素 (GH) 受体和结合蛋白信使核糖核酸 GHR1 具有性二态性并受 GH 调节。
作者：
W. Baumbach;B. Bingham
在大鼠中，选择性剪接的信使 RNA (mRNA) 种类编码 GH 受体 (GHR) 和 GH 结合蛋白 (GHBP)。此外，这些 mRNA 在 5'-非翻译区进行选择性剪接，产生至少两类具有不同第一外显子和相同编码区的 GHR 和 GHBP mRNA。这些替代的第一个外显子定义了 GHR 和 GHBP mRNA 的两个独特类别（称为 GHR1 和 GHR2）。 GHR1 类 RNA 仅在肝脏中表达，在女性中比男性丰富得多，并且在怀孕期间尤其丰富。 GHR1 RNA 在发育过程中比 GHR2 更晚被诱导。还可能存在其他类别的 GHR 和 GHBP RNA。 GHR1 第一个外显子的基因组结构揭示了一个推定的启动子区域，没有 TATA 盒、CAAT 盒或其他表明特定反应的序列元件。使用体内方法来研究 GHR1 表达的调节。在雌性大鼠中，性腺切除术被发现会降低肝脏中稳态 GHR1 RNA 水平的百分比，而雄性大鼠去势会导致 GHR1 RNA 的诱导。然而，雌激素或睾酮的短期治疗效果甚微，这表明 GHR1 表达的直接调节可能是通过性腺类固醇以外的效应物发生的。垂体切除术消除了女性体内的 GHR1 RNA。单次注射GH治疗垂体切除的雌性和去势雄性并没有显着诱导GHR1 RNA，但连续输注GH治疗却能显着诱导GHR1 RNA。对于每种处理，观察到非 GHR1 RNA 水平几乎没有变化。结果表明：1）大鼠肝脏中总GHR和GHBP RNA中观察到的性别二态性归因于GHR1类RNA的性别二态性表达； 2) 大鼠 GH 释放的性别二态性模式调节 GHR1 类 RNA； 3）在性腺切除术、垂体切除术、GH治疗和妊娠中观察到的GHR和GHBP表达的变化最好归因于GHR1调节； 4) 由于 GHR1 是肝脏特异性的，因此观察到的血清 GHBP 浓度因性类固醇、GH 模式和妊娠而增加的现象很可能源自肝脏。
In the rat, alternatively spliced messenger RNA (mRNA) species encode GH receptor (GHR) and GH-binding protein (GHBP). Additionally, these mRNAs are alternatively spliced in the 5'-untranslated region, resulting in at least two classes of GHR and GHBP mRNA with distinct first exons and identical coding regions. These alternative first exons define two unique classes of GHR and GHBP mRNA (called GHR1 and GHR2). The GHR1 class of RNA is expressed only in the liver, is far more abundant in females than males, and is particularly abundant during pregnancy. GHR1 RNA is induced later in development than is GHR2. Additional classes of GHR and GHBP RNA may also exist. The genomic structure of the GHR1 first exon reveals a putative promotor region with no TATA box, CAAT box, or other sequence elements suggesting specific responses. An in vivo approach was used to investigate the regulation of GHR1 expression. In female rats, gonadectomy was found to reduce the percentage of steady state GHR1 RNA levels in the liver, whereas male castration resulted in an induction of GHR1 RNA. However, short-term treatment with estrogen or testosterone had little effect, suggesting that direct regulation of GHR1 expression may occur through effector(s) other than gonadal steroids. Hypophysectomy abolished GHR1 RNA in females. Treatment of hypophysectomized females and castrated males with GH by single injection did not significantly induce GHR1 RNA, but treatment by continuous infusion of GH did. Little change in non-GHR1 RNA levels was observed for each of these treatments. The results suggest that: 1) the sexual dimorphism observed in total GHR and GHBP RNA in rat liver is attributable to the sexually dimorphic expression of the GHR1 class of RNA; 2) the sexually dimorphic pattern of GH release in rats regulates the GHR1 class of RNA; 3) changes in GHR and GHBP expression observed on gonadectomy, hypophysectomy, GH treatment, and pregnancy are best attributed to GHR1 regulation; and 4) since GHR1 is liver specific, the observed increases in serum GHBP concentration in response to sex steroids, GH pattern, and pregnancy are likely to originate from the liver.