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LHRH and its analogues are known to exert direct effects on the ovary. Herein we have described a direct inhibitory effect of an LHRH antagonist (Nal-Lys antagonist: antide) on the basal progesterone (P₄) and pregnenolone (P₅) production by luteal cells obtained from the day-8 pregnant rat. Luteal cells incubated with two doses of antide (10^–4 and 10^–7 M) for 24 or 48 h showed suppression of P₄ production. P₅ production was suppressed by both doses of antide within 12 h of incubation. Neither dose of antide interfered with P₅ production when the duration of incubation was extended beyond 12 h. The 20-dihydroprogesterone yield from the luteal cells treated with these doses of antide remained unaffected. We estimated the activities of the cholesterol side-chain cleavage (P450scc) enzyme (which is a key enzyme involved in the conversion of cholesterol to P₅) and 3β-hydroxysteroid dehydrogenase (3β-HSD) (which catalyses the conversion of P₅ to P₄) in the luteal cells treated with different doses of antide. Both doses of antide suppressed the activity of the P450scc enzyme after 12 h of incubation and the 3β-HSD content of the luteal cells after 48 h of incubation. These observations indicate that antide exerts a direct inhibitory effect at the level of the corpus luteum, that differential suppression of P₅ and P₄ during different periods of incubation with antide is due to a defect in either the P450scc or the 3β-HSD enzyme system, or both.

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