Abstract

We conducted a study of baseline hormone concentrations in a managed population of bottlenose dolphins (Tursiops truncatus). During this study, some participating males were periodically administered Megestrol acetate (MA, trade name Megace®) to suppress reproductive behavior. In mammals, MA is thought to bind with progesterone receptors and, consequently, inhibit the release of gonadotropin releasing hormone (GnRH) by the hypothalamus.³ This generally suppresses the hypothalamus-pituitary-gonad (HPG) axis resulting in reduced levels of gonadotropins. Megace also binds to corticosteroid receptors, although at lower affinities than their complementary hormones (e.g., cortisol), and has potential glucocorticoid activity that might influence the hypothalamus-pituitary-adrenal (HPA) axis.² Consequently, the administration of MA to alter animal behavior may have unintended consequences on aspects of hormonal regulation. We therefore further investigated the relationship between MA treatment and endogenous hormone concentrations in this population.

Bottlenose dolphins participating in this project resided at the U.S. Navy Marine Mammal Program (MMP, San Diego, CA) and were trained to voluntarily participate in blood and fecal sampling. Samples were collected every other week for one year and we compared ACTH and adrenal hormone concentrations (corticosteroids and catecholamines) from dolphins at varying MA doses (zero to 60 mg/day). Circulating ACTH, cortisol, epinephrine and norepinephrine concentrations, as well as concentrations of the fecal derivatives of cortisol were measured using commercially available RIA kits. To validate commercial kits for use in bottlenose dolphins, diluted sample substrate was compared against the standard curve for parallelism. Circulating cortisol concentrations were uniformly low among MMP dolphins, near the detection limit of the assay (5.5 nM). Therefore, the metabolized derivatives of fecal cortisol were used to assess cortisol excretion.¹ Linear mixed-model analysis was used to compare hormone concentrations among MA doses, with dose level as a fixed effect and individual dolphin as a random effect. MA dose had a significant influence on the HPA axis, suppressing both ACTH concentration (F_8,144 = 82.8, p < 0.001) and cortisol excretion (F_8,77 = 45.0, p < 0.01) at doses as low as 10 mg/day (post-hoc comparison, p < 0.05). In addition, epinephrine concentrations were also lower when on MA (F_7,69 = 38.2, p < 0.05) while we did not detect an influence on norepinephrine concentrations (p > 0.05). Hormone levels appear to recover within weeks of cessation of MA treatment. The impact of MA on certain endogenous hormones indicates that MA has a greater influence on non-target hormones than that reported for other species.

Acknowledgments

We thank the training staff at the National Marine Mammal Foundation and the U.S. Navy Marine Mammal Program for their assistance in sample collection. This work was funded by the Office of Naval Research (grant number N000141110436) and approved by the National Marine Mammal Foundation Institutional Animal Care and Use Committee.

* Presenting author

Literature Cited

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