Induction of luteinizing hormone (LH) release and ovulation in rats, hamsters, and rabbits by synthetic luteinizing hormone-releasing factor (LRF).

Abstract

The efficacy of synthetic LRF in inducing LH release in the estrogen progesteroneblocked, chronically ovariectomized rat and ovulation in the cycling rat, hamster, and rabbit was established. Synthetic LRF was highly effective by various modes of administration, but there were differences in the time course and magnitude of the LH release response depending on the route, and differences in the quantity of LRF required to induce ovulation depending on the species. Following the intracarotid injection of LRF, serum LH peaked at 10 min and a linear log dose—response relationship was obtained over the range of 1 to 5O ng per rat. After the oral administration of 1 mg of LRF, serum LH concentrations were increased to a maximum (27– fold) by 30 min, then steadily declined, reaching basal levels by 90 min. A sustained effect of LRF (10 or 100 μg/rat) on LH secretion was noted following intravaginal dosing using a repository vehicle; serum LH was significantly increased by 10 min, maximal at 30 min, and remained elevated for at least an additional 90 min. LRF, given sc in μg quantities or orally in mg amounts, induced ovulation in chlorpromazine (CPZ)—blocked proestrous rats. The lowest sc dose of LRF yielding 100% ovulation (MED100) in the CPZ—blocked proestrous rat was 1 μg (3.7 μg/kg body wt) whereas in the phenobarbital—blocked proestrus hamster the MED100 was 0.01 μg (0.11 μg/kg body wt). In estrous rabbits, an iv dose of 2.5 μg of LRF (0.88 μg/kg body wt) was the MED100 for induction of ovulation, a value intermediate to that of the rat and hamster. The administration of pharmacological doses (1000 times or more the MED100) to cycling rats, hamsters, or rabbits at a time coincident with the endogenous surge of ovulating hormone failed to induce superovulation. These results demonstrate that synthetic LRF is highly efficacious by several routes of administration in stimulating LH release and ovulation in three rodent species. (Endocrinology92: 1515, 1973)