GnRH Agonists in Avian and Exotic Patients: Opportunities and Challenges

Gonadotropin-releasing hormone agonist (GnRHa) peptide drugs including leuprolide and deslorelin have been successfully used for decades in humans, domestic animals, free-ranging wildlife and animals in zoological facilities, and more recently in avian and exotic companion animals. Typical uses for GnRHa include reproductive stimulation, reproductive suppression (contraception or hormoneresponsive disease suppression), and control of aggression. Species respond differently to various GnRHa medications, in part due to taxonomic differences in neuroendocrine physiology but also due to differences in drug formulation. The decision of which GnRHa to prescribe in a particular patient depends on the patient’s species physiology, the intended purpose (eg, reproductive stimulation versus suppression), the desired duration of effect, legal restrictions, and product availability/cost. For avian and exotic companion animal patients in the United States, leuprolide (depot form) is a GnRHa option that is expensive, but legal for extra-label use in a broad variety of species. In contrast, deslorelin is less expensive, but is frequently unavailable, and its use is prohibited in pets other than ferrets with adrenocortical disease. Neuroendocrine Physiology Related to GnRH Agonists The hypothalamus, anterior pituitary gland and gonads are the most important organs involved in the pharmacodynamics of GnRHa.1 Normally, specific neurons in the hypothalamus produce pulses of endogenous gonadotropin-releasing hormone (GnRH), which is transported via the hypophyseal portal system to the anterior pituitary gland and bound by GnRH receptors there, causing the anterior pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH) into the systemic circulation. Despite their female-based names, FSH and LH have effects in both females and males. In testes, FSH stimulates Sertoli cells to produce nutrients necessary for spermatogenesis and LH stimulates testosterone production by Leydig cells, which then supports spermatogenesis. Testosterone also targets many tissues outside the testes, including those responsible for sexspecific secondary characteristics, as well as the regions of the brain that mediate aggression, territoriality, courtship and mating.2 In ovaries, FSH stimulates follicles to produce estradiol, which causes changes throughout the body (eg, vaginal mucus consistency, vulvar appearance, sex skin coloration) as well as inducing estrous behavior. Once serum estradiol concentrations become high enough, feedback to the hypothalamus causes a pulse of GnRH to be released, and this causes an LH surge, which causes ovulation to occur. As the ruptured follicle luteinizes, progesterone is produced. This is an example of a positive feedback loop which exists between hormone production in the gonads (estradiol, progesterone, testosterone) and hypothalamic GnRH release. Negative feedback loops also exist between all components of the hypothalamic-pituitary-gonad axis; for example, high serum concentrations of estradiol, progesterone or testosterone cause the hypothalamus to release less GnRH, avoiding overstimulation of target tissues.