The effect of clomiphene on the ovulation induced with PMS treatment in immaturerats

Abstract

The effect of clomiphene on the ovulation induced with PMS treatment was investigated in immature rats.
PMS (3 IU) was injected subcutaneously to rats of 25 days of age at 9 : 300: 00 A. M.. The animals were killed at 74 hrs. after PMS injection and the tubal ova were checked under the dissecting microscope. Clomiphene (clomiphene citrate) was injecuted subcutaneously as a 30% ethanol-saline solution in the dose per 100 g of body weight. Vaginal smear and weight of organs (ovaries, uterus, pituitary) were also examined at autopsy.
Results obtained wereas follows
: 1) When the clomiphene was injected at 12 hrs. after PMS injection, 5 mg and 1.25 mg of clomiphene inhibited the ovulation completely, while 500 μginhibited in the rate of 60 % and 250 μg had no effect on the ovulation (Table 1).
2) Two doses of clomiphene (5 mg, 500 pg) were injected at various times after PMS injection. In the case of 5 mg treatment (Table 2), the ovulation was inhibited in the rate of 6080% at 0 and 2736 hrs. after PMS injection.
The complete inhibition of ovulation with clomiphene treatment was observed during 324hrs. after PMS injection. Following clomiphene injection at 39 hrs. after PMS injection had no inhi-bitory effect on the ovulation. In the case of 500 μg treatment (Table 3), the inhibition of ovulation was observed in the rate of 60% at 3to 24 hrs. after PMS injection. The inhibitory effect of clomiphene treatment was not shown at 27 hrs. after PMS injection.
In many cases that the ovulation occured by the treatment of two doses of clomiphene, the weight of uterus was smaller than that of control (PMS only). On the otherhand, the ovarian and pituitary weights and vaginal smear were not clearly influenced by clomiphene (Table 2, 3).
3) In the case of HCG (10 IU) injection of 54 hrs. after PMS injection to rats which were given clomiphene (5 mg) at 12 hrs. after PMS injection, ovulation was induced in all animals. In the rats of PMS and clomiphene treatment, tubal ovawere found in all animals at 98 hrs. after PMS injection, so that the delay of ovulation for 24 hrs. is recognized (Table 4).
4) When 0.5 μg of estradiol-17 βwas administered at 3 to 6 hrs. after PMS injection to rats in which the ovulation might be inhibited with clomiphene treatment (clomiphene 1 mg: 6 hrs. after PMS injection), the inhibitory effect of clomiphene was completely overcome. However, in these cases the depletion of uterine weight was not restored.
Since it is known that clomiphene competes with estrogen concerning to estrogen receptor in hypothalamus-pituitary system, it is suggested that endogenous estrogen following to PMS treatment plays an important role on the induced ovulation with PMS treatment.