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J. Biol. Chem., Vol. 262, Issue 15, 7076-7080, 05, 1987
AG Pucell, FM Bumpus and A Husain
Angiotensin II receptor agonist (125I-angiotensin II) and antagonist
(125I-[Sar1,Ile8]angiotensin II) bind in a specific and saturable manner to
rat ovarian membranes. Agonist and antagonist binding affinity (KD
approximately 0.5 nM) and the number of sites estimated (Bmax approximately
60 fmol/mg of protein) were similar. Dissociation of receptor-bound agonist
was more rapid than the dissociation of receptor-bound antagonist, and
agonist, but not antagonist, dissociation from the receptor was accelerated
by GTP gamma S. A 0-150 mM increase in Na+ produced a 27% increase in the
KD of agonist binding. Antagonist binding was not modified by Na+. These
studies suggest that both agonist and antagonist identify putative
angiotensin II receptors in the ovary but that the properties of agonist
and antagonist binding are distinct. Angiotensin II antagonist binding
sites are present on the granulosa cell layer of rat ovarian follicles
(Speth, R. C., Bumpus, F. M., and Husain, A. (1986) Eur. J. Pharmacol. 130,
351-352). To determine the role of angiotensin II in ovarian function, we
examined angiotensin II receptors and function during the onset of puberty.
High affinity and low capacity angiotensin II receptors were present in
ovaries from immature rats. After pregnant mare's serum gonadotropin
induced ovulation in immature rats, antagonist binding to total ovarian
membranes increased over 3-fold. In vitro incubation of peripubertal
ovaries with 1 microM angiotensin II produced a stimulation of estrogen,
but not progesterone, secretion. This steroidogenic effect of angiotensin
II was most pronounced in the luteal phase of the estrus cycle. These
studies point toward the involvement of angiotensin II in the regulation of
ovarian function, possibly through modulation of follicular estrogen
levels.
Rat ovarian angiotensin II receptors. Characterization and coupling to estrogen secretion
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