長庚婦產通訊--第42期
 

Intermedin:一個的新胜太荷爾蒙

林口院區 張嘉琳 醫師

  Calcitonin, calcitonin gene-related peptides (CGRP), adrenomedullinamylin屬於同一胜太荷爾蒙家族,分別在調節血鈣濃度、調控神經傳導維持心臟血管恆定、維持血壓平衡和調節血糖代謝上扮演重要角色。我們最近利用研究基因生物資訊學,發現一個屬於此荷爾蒙家族的新胜太—intermedin (IMD)。人類成熟的intermedin40個胺基酸組成,主要表現於腦下垂體前葉之促腎上腺皮質細胞。Intermedin主要經由與CRLR/RAMPs受體複合體結合,刺激cAMP釋放來傳達訊息。在老鼠身上投予intermedin能有效降低老鼠血壓和增加心跳速度。卵巢切除的老鼠腦下垂體intermedin的表現量會下降10倍,而對已被切除卵巢的老鼠投予動情激素,則可以有效的恢復intermedin在腦下垂體中的表現量至與正常鼠相同的水平。綜合上述,我們了解intermedin可以調節心臟血管系統,並可經由動情激素來調控。Morimoto等人利用radioimmunoassayimmunocytochemistry 兩種方法發現Immunoreactive-IMD可以在human brains, pituitaries, left ventricles of hearts kidneys被偵測到而利用Immunocytochemistry 可以發現 paraventricular and supraoptic nuclei of hypothalamus, anterior and posterior lobes of pituitary, cardiomyocytes, pericardial adipocytes, vascular endothelial cells of pericardial veins, vascular smooth muscle cells of coronary arteries and renal arterioles as well as in renal tubular cells都有 IMD的表現 (Fig.2- 4).

經由後續實驗發現:

患有慢性缺氧性肺動脈高血壓的老鼠其體內IMD/ADM2的濃度會增加。將20隻公鼠以隨機取樣方式分成缺氧的實驗組及正常的對照組觀察4週,缺氧實驗組安置於氧含量9%-11%,CO2含量維持低於3%的缺氧空間共4週(每天8小時每週6天)而對照組的老鼠則安置於正常室內空氣中。血漿及右心室組織中的IMDADM的含量是以放射免疫測定儀來測定,其受體CRLR, RAMP1, RAMP2, RAMP3等的mRNA量則以RT-PCR測定。結果顯示實驗組其平均肺動脈壓(mPAP)高於對照組,缺氧組的血

漿及右心室組織中的ADM含量比對照組增加了1.26-1.68倍,IMD含量增加了0.90-1.19 倍。而RT-PCR測定mRNA量結果ADMIMDRAMP2於缺氧組各增加:155.1%80.9%52.9%而兩組之間的CRLR, RAMP1, RAMP3mRNA含量並沒有明顯的差異。

  1. 經老鼠腦室投與IMD,可刺激老鼠下視丘分泌催產素。
  2. IMD能有效降低老鼠血壓,且此降低老鼠血壓的效果對於懷孕期間的老鼠影響更為顯著。
  3. 於老鼠中期懷孕期間靜脈注射IMD結抗劑後,可引發胎盤凋零,引起胎兒生長遲緩。
縱合言之,IMD 是一個對心臟血管和內分泌生殖系統均有相當效力之新的胜?荷爾蒙。

Reference

  1. Intermedin is a calcitonin/calcitonin gene-related peptide family peptide acting through the calcitonin receptor-like receptor/receptor activity-modifying protein receptor complexes
    J Biol Chem. 2004 Feb 20; 279(8):7264-74. Epub 2003 Nov 13. Roh J, Chang CL, Bhalla A, Klein C, Hsu SY.
  2. Intermedin functions as a pituitary paracrine factor regulating prolactin release.Mol Endocrinol. 2005 Nov; 19(11):2824-38. Epub 2005 Jul 7. Chang CL, Roh J, Park JI, Klein C, Cushman N, Haberberger RV, Hsu SY.
  3. Adrenomedullin 2 (AM2)/intermedin is a more potent activator of hypothalamic oxytocin-secreting neurons than AM possibly through an unidentified receptor in rats.
    Peptides. 2007 Feb 14; [Epub ahead of print]
    Hashimoto H, Hyodo S, Kawasaki M, Shibata M, Saito T, Suzuki H, Otsubo H, Yokoyama T, Fujihara H, Higuchi T, Takei Y, Ueta Y.
  4. Adrenomedullin-2, a novel calcitonin/calcitonin-gene-related peptide family peptide, relaxes rat mesenteric artery: influence of pregnancy.
    Endocrinology. 2007 Apr; 148(4):1727-35. Epub 2007 Jan 11. Chauhan M, Ross GR, Yallampalli U, Yallampalli C.
  5. Adrenomedullin 2 antagonist infusion to rats during midgestation causes fetoplacental growth restriction through apoptosis.
    Biol Reprod. 2006 Dec; 75(6):940-7. Epub 2006 Sep 13. Chauhan M, Yallampalli U, Reed L, Yallampalli C.
  6. Expression of adrenomedullin2/intermedin in human brain, heart, and kidney.
    Peptides. 2007 May; 28(5):1095-103. Epub 2007 Feb 8. Morimoto R, Satoh F, Murakami O, Totsune K, Suzuki T, Sasano H, Ito S, Takahashi K.
 
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