Effects of domperidone and thyrotropin-releasing hormone on secretion of luteinizing hormone and prolactin during the luteal phase and following induction of luteal regression in sheep

Abstract

Effects of domperidone, a peripheral dopamine receptor antagonist, on secretion of LH and prolactin were studied during the luteal phase and following administration of PGF 2α. Since hyperprolactinemia has been reported to inhibit secretion of LH in ewes, effects of thyrotropin-releasing hormone (TRH) also were examined. Ewes 8–10 days post-estrus were assigned to be treated with: 1) vehicle (n=5); 2) 0.3 mg domperidone (n=6); 3) 1.0 mg domperidone (n=6); 4) 3 μg TRH (n=6); or 5) 10μg TRH (n=6) every 4 hours for 60 hr. Luteal regression was induced with PGF 2α at 12 hr after initiation of treatments. During the luteal phase, pulses of LH were more frequent (P<.05) and the amplitudes of these were higher (P<.05) in ewes treated with domperidone or TRH than in control ewes. These changes in LH occured even though each treatment elevated markedly concentrations of prolactin in plasma. After induction of luteal regression, mean of LH and frequency of LH discharges were similar in all groups. However, in ewes treated with the 1.0 mg/4 hr dose of domperidone the pulse amplitude was greater than in the other groups (2.3 vs 1.1 ng/ml). Dose-response relationships and the magnitude of the prolactin release following domperidone or TRH varied with time. Treatments did not affect the timing of the LH surge or the increase in progesterone associated with the subsequent cycle. Based on these data we conclude that: 1) endogenous hypothalamic dopamine mediates some of the inhibitory effects of progesterone on secretion of LH and prolactin; 2) dopamine limits the extent of the usual follicular phase increase in prolactin; 3) acute hyperprolactinemia does not inhibit the secretion of LH; and 4) administration of TRH can increase the frequency and amplitude of LH pulse frequency and amplitude in sheep in the luteal phase of LH in sheep.