UNDERSTANDING PROLACTIN REGULATION AND DETERMINING THE EFFICACY OF CABERGOLINE AND DOMPERIDONE TO MITIGATE PROLACTIN-ASSOCIATED OVARIAN CYCLE PROBLEMS IN ZOO AFRICAN ELEPHANTS (LOXODONTA AFRICANA ).

ABSTRACT

Perturbations in serum prolactin secretion, both over- and underproduction, are observed in zoo African elephants (Loxodonta africana) that exhibit abnormal ovarian cycles. Similar prolactin problems are associated with infertility in other species. Pituitary prolactin is held under constant inhibition by a hypothalamic-derived neurotransmitter, dopamine; thus, regulation by exogenous treatment with agonists or antagonists may be capable of reinitiating normal ovarian cycles. This study tested the efficacy of oral administration of cabergoline (agonist) and domperidone (antagonist) as possible treatments for hyperprolactinemia or chronic low prolactin, respectively. Hyperprolactinemic (overall mean prolactin, >30 ng/ml), acyclic elephants were administered oral cabergoline (2 mg, n = 4) or placebo (dextrose capsule, n = 4) twice weekly. Overall mean prolactin concentration decreased in treated females compared with controls (32.22 ± 14.75 vs 77.53 ± 0.96 ng/ml; P = 0.01). Interestingly, overall mean progestagen concentrations also increased slightly (P < 0.05) in treated females (0.15 ± 0.01 ng/ml) compared with controls (0.07 ± 0.01 ng/ml), but no reinitation of normal cyclic patterns was observed. Chronic low prolactin (overall mean prolactin, <10 ng/ml), acyclic females were orally administered domperidone (2 g/day, n = 4) or placebo (dextrose capsule, n = 4) for 4 wk, followed by 8 wk of no treatment (four cycles) to simulate the prolactin pattern observed in normal cycling elephants. Overall mean prolactin concentrations increased (P = 0.005) during domperidone treatment (21.77 ± 3.69 ng/ml) compared with controls (5.77 ± 0.46 ng/ml), but progestagen concentrations were unaltered. Prolactin regulation by dopamine was confirmed by expected responses to dopamine agonist and antagonist treatment. Although prolactin concentrations were successfully reduced by cabergoline, and domperidone initiated the expected cyclic prolactin pattern, neither treatment induced normal ovarian activity.