Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy

Tsunekazu Matsumoto, Norimasa Sagawa, Masashi Mukoyama, Issei Tanaka, Hiroaki Itoh, Masahisa Goto, Hiroshi Itoh, Masatsugu Horiuchi, Victor J. Dzau, Takahide Mori, Kazuwa Nakao

研究成果: Article査読

32 被引用数 (Scopus)

抄録

Angiotensin II (Ang II) acts on at least two receptor subtypes, type 1 (AT1) and type 2 (AT2). The AT2 receptor is abundant in the fetus and decreases rapidly after birth. The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role in reproduction. To explore the roles and regulation of the AT2 receptor in human uterus and to examine whether its expression is related to the proliferative characteristics of leiomyoma, we studied Ang II receptor gene expressions in nonpregnant and pregnant myometrium and in uterine leiomyomas obtained from patients who underwent gynecological surgery. Receptor binding studies revealed that all samples exhibited high-affinity binding for [Ser1,Ile8]Ang II, most (>90%) of which was of the AT2 subtype. In nonpregnant myometrium (n = 5), receptor density [maximum binding capacity (B(max))] and dissociation constant (K(d)) for AT2-selective CGP42112A were 287 ± 46 fmol/mg protein and 0.48 ± 0.09 nM, respectively. In the myometrium of early (n = 6) and late pregnancy (n = 3), B(max) for the AT2 receptor was significantly decreased (62 ± 17 and 25 ± 6 fmol/mg protein, respectively). Furthermore, administration of combined oral contraceptive pills induced a comparable reduction in AT2 B(max) (54 ± 12 fmol/mg protein, n = 4). AT2 B(max) or K(d) values in uterine leiomyomas from nonpregnant women showed no significant differences from those in nonpregnant myometrium. Changes of AT2 B(max) in uterine leiomyomas during pregnancy or with oral contraceptives were similar to those in the myometrium. Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter. Although the AT1 receptor mRNA expression did not change significantly, the AT2 receptor mRNA level was significantly decreased during pregnancy or with oral contraceptives. These results indicate that AT1 and AT2 receptors are expressed in human myometrium and uterine leiomyoma, in which the AT2 receptor is predominant, AT2 receptor gene expression is down-regulated during pregnancy, possibly mediated by sex steroids.

本文言語English
ページ(範囲)4366-4372
ページ数7
ジャーナルJournal of Clinical Endocrinology and Metabolism
81
12
DOI
出版ステータスPublished - 1996 12月 19
外部発表はい

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 内分泌学
  • 臨床生化学
  • 生化学、医学

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