Effect of Cis- and Trans-Clomiphene on the Uterine Blood Flow of Oophorectomized Ewes

Abstract

Changes in the left uterine artery blood flow (UBF) after intraarterial administration of estradiol-17β and cis- and trans-clomiphene citrate to conscious, oophorectomized ewes were monitored by chronically implanted electromagnetic flow probes. Cis-clomiphene produced UBF increases comparable to or greater than those produced by estradiol-17β but at dose levels 20 times greater. Comparison of UBF response curves for cis-clomiphene with those for estradiol-17β showed a delayed onset of initial vasodilation and a delayed peak response. The duration of uterine vasodilation produced by cis-clomiphene was dose-dependent and exceeded that produced by estradiol-17β. Similar responses were observed with trans-clomiphene but at dose levels at least 1,000 times those of estradiol-17β. The characteristics of clomiphene-induced UBF responses that differed from those after estradiol-17β may reflect differences in estrogen receptor activation between the compounds.

Uterine blood flow and prostaglandin levels in ovariectomized rabbits

“…In conscious ovariectomized sheep, a maximal effect on uterine blood flow was observed with a dose of 0-5 µg oestradiol-17ß/kg intra-arterially, and this occurred at 2 h; the effect was still observable 12 h after injection. Doses up to 10 µg oestradiol-17ß/kg produced no greater effect than 0-5 µg/kg (Still & Greiss, 1976).…”

“…In the present experiments, the dose of oestradiol used (25 µg/rabbit, approximately 5-6-7-1 µg/kg) was chosen because it is known to affect ovum transport (Saksena & Harper, 1975). Although this dose of oestradiol is in the pharmacological range, the observations of Still & Greiss (1976) indicate that our results for blood flow should not be different from those induced by more physiological doses of oestrogen. The decline observed by us is similar to that reported by Still & Greiss (1976), but no direct comparison is possible since these authors give no absolute values, only percentage change from controls.…”

Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol‐17β‐treated, intact follicular and pregnant sheep

“…Indirect evidence such as the order of potency of various oestrogens suggests that the oestrogen‐induced increase in UBF occurs through an oestrogen receptor (ER)‐mediated mechanism. Furthermore, the pattern and efficacy of the oestrogen‐induced increase in UBF is similar regardless of the oestrogen used including E 2 β, oestrone, oestriol, Premarin, raloxifene and extremely high doses of the anti‐oestrogen trans ‐clomiphene (Greiss & Anderson, 1970; Killam et al 1973; Resnik et al 1974; Still & Greiss, 1976; Rosenfeld & Rivera, 1978; Levine et al 1984; Zoma et al 2000; Clark et al 2000). The assumption that this is a receptor‐mediated process was also suggested indirectly by one study in which Lineweaver‐Burk plots were developed using the reciprocal of UBF responses versus the dose of oestradiol and catechol oestrogens.…”