A possible involvement of oestrogens in regulating the ovulatory release of luteinizing hormone (LH) has been explored by using an oestrogenantagonist, clomiphene. When given orally in the afternoon on the day before pro-oestrus to rats with a 4-day cycle, the compound prevented ovulation on the morning of oestrus. This was not associated with interference with vaginal cornification, uterine ballooning or mating. Similarly, clomiphene prevented ovulation in hamsters when given at a corresponding stage of the cycle. In adult rats ovulation could be fully restored by the intravenous administration of LH or LH releasing factor at 14.00 hr. on the day of pro-oestrus. Oestradiol benzoate given simultaneously with clomiphene on the day before pro-oestrus or the stimulus provided by mating on the night of pro-oestrus were also effective in this respect. It is implicit in these findings that clomiphene interferes with ovulation by virtue of its anti-oestrogenicity. This indicates that a positive feedback of oestrogen is an integral part of the chain of events culminating in the ovulatory release of LH in the reproductive cycle.
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