Studies on the Anti-Ovulatory and Ovulatory Action of Clomiphene Citrate in the Rat

Abstract

To study the site and mechanism of its ovulation-inhibiting effect, clomiphene citrate was implanted bilaterally into the hypothalamus and hypophysis of adult di-oestrous rats and of prepuberal females which were also treated with oestradiol benzoate. The results suggest that this effect is primarily due to the action of clomiphene on the anterior pituitary. The anti-oestrogenic activity of clomiphene may prevent the action of oestrogen on the hypophysis, thus suppressing the increased gonadotrophin secretion leading to ovulation. The ovulation-inducing effect of clomiphene was investigated in adult female rats which had been made anovulatory by destruction of the suprachiasmatic nuclei. Bilateral implantation of a small quantity of clomiphene citrate into the ventromedial-arcuate region resulted in corpus luteum formation and ovulation in these animals. A direct stimulation of the central hypothalamus is thought to be responsible for the ovulatory action of clomiphene in rats with cerebral lesions.

Effect of Clomiphene Citrate on the Ovary of a Wild Rat, <i>Bandicota bengalensis</i>

“…la). While in the laboratory rat Docke [14] reported a complete inhibition of ovulation with 3.0 mgclomiphene/kg. in the bandicoot rat this dose inhibited ovulation only in 35% of the rats.…”

“…suppresses gonadotropins [22] and has antizygotic [35], anti-implantation [6,44] and anti-enbryonic [8] effects. However, as in anovulatory women, clomiphene also induces ovulation in pseudopregnant [43] and in artificially-induced anovulatory rats [13], but it inhibits ovulation in normally cycling rats [14].…”