In vivo investigation of estrogen regulation of adrenal and renal angiotensin (AT1) receptor expression by PET.
The renin angiotensin system (RAS) has been implicated as one mediator of the cardiovascular effects of estrogen. Since changes in angiotensin type 1 (AT(1)) receptor expression are central to modulation of the RAS, we used the noninvasive PET imaging technique to study for the in vivo effects of estrogen on membrane and intracellular AT(1) receptors.


METHODS
Dynamic PET measurements of canine AT(1) (cAT(1)) receptors using the radiolabeled AT(1) receptor antagonist, (11)C-L-159,884, were performed during 2-wk consecutive periods of estrogen deprivation induced by ovariectomy and 17beta-estradiol (E(2)) replacement.


RESULTS
Kinetic modeling of time-activity curves in the kidney and adrenal showed lower receptor expression in the estrogen replete state (21% and 30% decrease in Gjedde-Patlak slope, influx constant, respectively). These in vivo findings correlated with in vitro radioligand-binding assays with (125)I-[Sar(1),Ile(8)]angiotensin II showing reduced AT(1) receptor number in the adrenal (35%), glomeruli (30%), myocardium (35%), and liver (21%) in the estrogen-replenished compared with estrogen-depleted animals.


CONCLUSIONS
Although other endogenous systems are known to regulate AT(1) receptors and could compete with estrogenic actions, these PET studies reveal that estrogen attenuates AT(1) receptor expression in vivo. Thus, estrogen modulation of AT(1) receptors may contribute to the cardiovascular protective effects associated with estrogen.
Owonikoko
Taofeek K
TK
Division of Nuclear Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Fabucci
Maria E
ME
Brown
Philip R
PR
Nisar
Nighat
N
Hilton
John
J
Mathews
William B
WB
Ravert
Hayden T
HT
Rauseo
Paige
P
Sandberg
Kathryn
K
Dannals
Robert F
RF
Szabo
Zsolt
Z
D000311:Adrenal Glands / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D007093:Imidazoles / Q000493:pharmacokinetics*; D007668:Kidney / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D004967:Estrogens; D007093:Imidazoles; D011725:Pyridines; D019275:Radiopharmaceuticals; D044140:Receptor, Angiotensin, Type 1; C099071:L 159884; D004958:Estradiol