Cm. Cannon et al., EFFECT OF A23187 OR ANGIOTENSIN-II ON OVARIAN METALLOPROTEINASE INHIBITORS AND STEROIDOGENESIS IN RATS, Journal of Reproduction and Fertility, 111(1), 1997, pp. 71-79
The present study examined the effect of the calcium ionophore A23187
or angiotensin II (AII) on the expression of ovarian metalloproteinase
inhibitor and activity in rat granulosa cells and intact ovaries. Gra
nulosa cells were collected from rats primed with pregnant mares' seru
m gonadotrophin (PMSG) and cultured for 24 h with A23187, AII, or the
AII receptor antagonist, saralasin, in the presence or absence of LH.
Metalloproteinase inhibitor activity and progesterone concentrations w
ere determined in the media. In the A23187 experiment, addition of A23
187 to granulosa cells, cultured without LH, decreased inhibitor activ
ity, especially at the concentrations of 10 and 100 mu mol l(-1) (decr
ease to 33 +/- 7% and 31 +/- 5% of control culture values, respectivel
y). Addition of LH to the media increased inhibitor activity 3.04 +/-
0.39 times compared with the control; however, A23187 (10 and 100 mu m
ol l(-1), in the presence of LH, decreased inhibitor activity by appro
ximately 67%. The ionophore had disparate effects on progesterone prod
uction. Without LH, A23187 increased progesterone production by 2.96 /- 0.47 times at 10 mu mol l(-1) and by 5.53 +/- 0.65 times at 100 mu
mol l(-1). However, in LH-stimulated cells, progesterone was inhibited
by A23187 at 1 and 10 mu mol l(-1) but was unchanged at 100 mu mol l(
-1). In the angiotensin experiment, addition of AII (0-10 000 nmol l(-
1)) or saralasin (1 mu mol l(-1)) did not affect inhibitor activity or
progesterone concentrations compared with control values in the absen
ce or presence of LH. For the angiotensin experiment in vivo, PMSG-pri
med rats were injected with hCG followed by saralasin (10 mmol l(-1))
1 or 3 h later and killed at 4, 8, or 12 h after hCG. Expression of th
e ovarian tissue inhibitor of metalloproteinase-1 (TIMP-1) increased b
y 1.7 times at 4 h, 3.3 times at 8 h, and 3.0 times at 12 h after hCG
compared with values in ovaries collected at the time of hCG injection
. Administration of saralasin at 1 or 3 h after hCG had no effect on e
xpression of TIMP-1 or on serum concentrations of progesterone or oest
radiol. In summary, A23187 decreased granulosa cell-derived inhibitor
activity, whereas AII had no effect. We propose that calcium may play
a role in modulating proteolysis associated with ovulation, while AII
does not appear to regulate ovarian metalloproteinase inhibitor activi
ty.