Estrogen upregulates renal angiotensin II AT(2) receptors.
AT(2) receptors may act in opposition to and in balance with AT(1) receptors, their stimulation having beneficial effects. We found renal AT(2) receptor expression in female mice higher than in male mice. We asked the question of whether such expression might be estrogen dependent. In male, female, ovariectomized, and estrogen-treated ovariectomized mice, we studied renal AT(1) and AT(2) receptors by immunocytochemistry and autoradiography, AT(2) receptor mRNA by RT-PCR, and cAMP, cGMP, and PGE(2) by RIA. AT(1) receptors predominated. AT(2) receptors were present in glomeruli, medullary rays, and inner medulla, and in female kidney capsule. AT(1) and AT(2) receptors colocalized in glomeruli. Female mice expressed fewer glomerular AT(1) receptors. Ovariectomy decreased AT(1) receptors in medullary rays and capsular AT(2) receptors. Estrogen administration normalized AT(1) receptors in medullary rays and increased AT(2) receptors predominantly in capsule and inner medulla, and also in glomeruli, medullary rays, and inner stripe of outer medulla. In medullas of estrogen-treated ovariectomized mice there was higher AT(2) receptor mRNA, decreased cGMP, and increased PGE(2) content. We propose that the protective effects of estrogen may be partially mediated through enhancement of AT(2) receptor stimulation.
Armando
Ines
I
Section on Pharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. ArmandoI@intra.nimh.nih.gov
Jezova
Miroslava
M
Juorio
Augusto V
AV
Terrón
José A
JA
Falcón-Neri
Alicia
A
Semino-Mora
Cristina
C
Imboden
Hans
H
Saavedra
Juan M
JM
D000818:Animals; D001345:Autoradiography; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D015232:Dinoprostone / Q000032:analysis; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007679:Kidney Medulla / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D004967:Estrogens; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000242:Cyclic AMP; D006152:Cyclic GMP; D015232:Dinoprostone