Baumbach W R, Bingham B
Agricultural Research Division, American Cyanamid Company, Princeton, New Jersey 08543.
Endocrinology. 1995 Feb;136(2):749-60. doi: 10.1210/endo.136.2.7835307.
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.
在大鼠中，可变剪接的信使核糖核酸（mRNA）种类编码生长激素受体（GHR）和生长激素结合蛋白（GHBP）。此外，这些mRNA在5'非翻译区进行可变剪接，产生至少两类具有不同首个外显子和相同编码区的GHR和GHBP mRNA。这些可变的首个外显子定义了两类独特的GHR和GHBP mRNA（称为GHR1和GHR2）。GHR1类RNA仅在肝脏中表达，在雌性中比雄性丰富得多，在怀孕期间尤其丰富。GHR1 RNA在发育后期比GHR2诱导得晚。可能还存在其他类别的GHR和GHBP RNA。GHR1首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。采用体内方法研究GHR1表达的调控。在雌性大鼠中，发现卵巢切除会降低肝脏中稳态GHR1 RNA水平的百分比，而雄性去势则导致GHR1 RNA的诱导。然而，短期用雌激素或睾酮治疗影响不大，这表明GHR1表达的直接调控可能通过性腺类固醇以外的效应物发生。垂体切除消除了雌性中的GHR1 RNA。对垂体切除的雌性和去势的雄性单次注射生长激素治疗并未显著诱导GHR1 RNA，但持续输注生长激素治疗则可以。这些治疗中每种治疗对非GHR1 RNA水平的影响很小。结果表明：1）在大鼠肝脏中观察到的总GHR和GHBP RNA中的性别二态性归因于GHR1类RNA的性别二态性表达；2）大鼠中生长激素释放的性别二态性模式调节GHR1类RNA；3）在性腺切除、垂体切除、生长激素治疗和怀孕时观察到的GHR和GHBP表达变化最好归因于GHR1的调节；4）由于GHR1是肝脏特异性的，因此观察到的血清GHBP浓度对性类固醇、生长激素模式和怀孕的反应增加可能源于肝脏。
