Immature alloxan-diabetic rats injected with pregnant mare's serum gonadotrophin (PMSG) do not ovulate and the LH surge is absent. In the present studies we have examined the effects of several insulin treatments on the LH surge and ovulation in alloxan-diabetic rats. Rats were made diabetic by injection of alloxan on day 24 of age. Only those rats with fasting blood glucose concentrations exceeding 180 mg/100 ml on day 27 were considered diabetic. PMSG was injected on day 30. Rats received insulin either by injection (2, 3, 4 or 6 IU/100 g/day; Ultralente B.I.D.) or by subcutaneous implants (Alzet osmotic minipumps; 1.8 or 2.4 IU/day). None of the diabetic rats without insulin treatment ovulated. Some of the animals in each insulin treatment group ovulated, however, the percentage of animals ovulating was highly variable from experiment to experiment when the insulin was given by injection. When insulin was administered by osmotic minipump, the results were more consistent, with at least 60% of the rats ovulating in each experiment. LH surges were found on the afternoon of presumed pro-oestrus (day 32) in diabetic insulin-treated rats which ovulated. In confirmation of previous results, rats without insulin treatment did not have LH surges. Although the site of insulin action has not been determined, these data indicate that the LH surge mechanism in the immature PMSG-treated rat is insulin-dependent.Experimental diabetes mellitus interrupts repro¬ ductive functions in rats and insulin therapy has been reported to restore gonadotrohin responses such as ovarian weight gain (Farina et al. 1971;Liu et al. 1972) and ovarian cholesterol depletion (Farina et al. 1971). Attempts to restore oestrous cycles in diabetic rats by insulin therapy have met with variable success (Chieri et al. 1969;Kim et al. 1960;Lawrence & Contopoulos 1960). Although insulin may partially ameliorate the derangement in cyclicity, the effects of insulin therapy on the pre-ovulatory LH surge are unknown. We have recently reported that alloxan-induced diabetes in PSMG-treated immature rats results in anovulation, which is due to the absence of the LH surge, rather than to a lack of ovarian responsiveness to gonadotrophins (Kirchick et al. 1978). Insulin in¬ jections restored ovulation in diabetic animals, but subsequent attempts were less successful. The pur¬ pose of this research was to determine the efficacy of insulin therapy in the restoration of the LH surge, ovulation and body weight gain in diabetic rats.
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