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Am J Physiol Endocrinol Metab 276: E25-E33, 1999;
0193-1849/99 $5.00
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Vol. 276, Issue 1, E25-E33, January 1999

Biological roles of angiotensin II via its type 2 receptor during rat follicle atresia

Eri Kotani1, Masataka Sugimoto2, Hachiroh Kamata2, Nobuharu Fujii2, Masahiro Saitoh1, Satoshi Usuki1, Takeshi Kubo1, Keifu Song3, Mizuo Miyazaki3, Kazuo Murakami2, and Hitoshi Miyazaki2

2 Gene Experiment Center, Institute of Applied Biochemistry, and 1 Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8572; and 3 Department of Pharmacology, Osaka Medical College, Osaka 569, Japan

Type 1 angiotensin II (ANG II) receptors play crucial roles in the regulation of blood pressure and fluid osmolarity, whereas the physiological roles of type 2 ANG II receptors (AT2) remain unclear. Because AT2 is expressed in atretic follicles where granulosa cells undergo apoptosis, we examined the space and time relationship between AT2 expression and follicle atresia in vivo and the effect of AT2 on follicle-stimulating hormone (FSH) actions in vitro. Binding studies, autoradiography, and RT-PCR of AT2 revealed that the AT2 content in granulosa cells was time dependently increased at both protein and mRNA levels in equine chorionic gonadotropin-treated immature female rats. This increase paralleled the progression of atresia. ANG II suppressed FSH-caused prevention of DNA fragmentation, increases in luteinizing hormone receptor content, and estrogen production through AT2 in cultured granulosa cells. Moreover, FSH-induced stimulation of extracellular signal-regulated kinase activity, critical for cell survival, was inhibited by AT2 stimulation. These results suggest that AT2 mediates the progression of follicle atresia through granulosa cell apoptosis by inhibiting FSH actions.

ovarian renin-angiotensin system; follicle-stimulating hormone; luteinizing hormone receptor; estrogen; polycystic ovary syndrome


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J. R. Pepperell, G. Nemeth, Y. Yamada, F. Naftolin, and M. Merino
Localized accumulation of angiotensin II and production of angiotensin-(1-7) in rat luteal cells and effects on steroidogenesis
Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E221 - E233.
[Abstract] [Full Text] [PDF]


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