GnRH Agonists to Control Wildlife Population

Lauren Busocker

INTRODUCTION

Human population growth along with expanded communities have increased human-
wildlife conflicts across the world. These conflicts started with amplified efforts in conservation
disputing with increased development, especially when the animals in question had the
possibility of being exploited for a profit (White and Ward, 2010). However, increased animal
welfare concerns and public objection to lethal culling required a new form of wildlife
management that did not mistreat the animal, but was still effective at controlling population
(Massei, Cowan, Gurney, and Ouy, 2010). In response, there have been peak interest in non-
lethal approaches like fertility control (Barr, Lurz, Shirley, and Rushton, 2002). Fertility control
has been advertised as a humane and ethical way of handling overpopulation of wildlife species
in heavily occupied areas (Kirkpatrick, Lyda, and Frank, 2011). Fertility control agents or
inhibitors contain chemicals that hinder oogenesis and spermatogenesis or block conception
(Massei and Cowan, 2014). The use of contraception to control wildlife populations began
around 1950, but included synthetic and natural types of steroids. Theses attempts were not
successful because health risk issues, toxicity, and detrimental effects on behavior (Kirkpatrick,
Lyda, and Frank, 2011). However, a new fertility inhibitor that has been introduced is the use of
gonadotropin-releasing hormone (GnRH) agonists (Baker, Wild, Connor, Ravivarapu, Dunn, and
Nett, 2004). Examples of GnRH agonists include, but are not limited to, leuprolide, deslorelin,
and GonaCon. Gonadotropin releasing hormone is a decapeptide that is secreted by the
hypothalamus and signals for the production of luteinizing hormone (LH) and follicle stimulating
hormone (FSH) in the anterior pituitary gland. LH and FSH are responsible for maintaining the
functions of either the ovaries or testes (Conn and Crowley, 1991). GnRH agonists can be used
to prevent reproduction by pituitary-gonadal axis suppression and by blocking the gonadotropin-
releasing hormone receptors in the pituitary gland (Herbert and Trigg, 2005).
 DISCUSSION

GnRH Agonists

Gonadotropin-releasing hormone agonists are an extremely potent peptides that, when

continuously administered, cause a sharp decline in the amount of LH and FSH being produced
in the pituitary gland. The result is less gonadal steroids being produces, causing hindrance in
follicular development or spermatogenesis. The overall effectiveness of gonadotropin releasing
hormone agonists rely on the type of agonist, dosage, and treatment length (Gobello 2007). For
example, evidence suggests that the long-lasting effects of GnRH agonists are dependent on the
dosage, and that constant administration of the agonist concludes in desensitization and gonadal
function failure (Clayton, 1979). Extended treatment with GnRH agonist results in a decrease in
the sensitivity of GnRH receptors, a suppression in the release of LH and FSH, and an overall
lack in the number of GnRH receptors present. In females, this also causes the prevention of any
follicular development since FSH levels have been held below the appropriate threshold for
development to take place (Herbert and Trigg, 2005). At the end of treatment ovarian function
returns to normal because the side effects of using a GnRH agonist are reversable, even after
continued use, but can cause abortions if used during breeding seasons (Baker, Wild, Connor,
Ravivarapu, Dunn, and Nett, 2004). Recently this method of contraception has been tested on
multiple species such as kangaroos, deer, seals, and other exotic wild animals (Adderton, 2004).
Sustained implantations of the GnRH agonist deslorelin have been effective in inhibiting cattle
reproduction for two years and have produced successful results in cats and wild dogs (Herbert
and Trigg 2005). However, the uses of a GnRH agonists as a method of contraception in wild
animals is limited because there must be constant deliverer of dosage for the entirely of the
season (Baker, Wild, Connor, Ravivarapu, Dunn, and Nett, 2004).

Research

Leuoprolide, a form of gonadotropin-releasing hormone agonist, was tested to evaluate

its effects on reproduction by comparisons with LH and progesterone levels in female deer. The
experiment called for thirteen mature females as well as two mature male deer. Within ninety
days five deer took 10 mg of leuprolide (group A). Five other deer were used as the control
group (group B) in order to compare the difference between normal pregnancy and reproductive
behavior verses the deer with the leuprolide in their system. Both groups were held in the same
meadow with the two mature male deer. The last three deer were used as a nonreproductive
control and were placed far from the males (group C). The second control group (group C) was
necessary because it served as a better comparison to the leuprolide treated deer than the deer
that were potentially pregnant. Progesterone and LH pulses were compared between the average
female deer (group C) and those with leuprolide (group A). The day treatment was given, five
deer (group A) were moved from the initial pasture to individual pens where they were sedated
and injected with leuprolide. Once the dear recovered from sedation, all five deer were returned
to the original pasture. Both control groups received nothing (groups B and C). The injection of
leuprolide prevented all five treated deer (group A) from pregnancy, in contrast to 100% of the
control group (group B) became pregnant. Injected female deer recovered with fully normal
ovarian function during the next breeding season and produced healthy offspring. Fawns that
were born to leuprolide-injected and control deer had similar weights and date of parturition,
providing evidence that the GnRH agonist treatment with leuprolide was reversible.

The agonist prevented pregnancy through the suppression of luteinizing hormone levels
for the entirety of the breeding season (Fig. 1). Leuprolide reduced the amount of LH in the
system of treated deer (group A) from 9.162 ng ml before treatment to a mere 0.246 ng ml by
day 45. LH levels remained significantly lower in treated females (group A) than in the control
group (group C) up until day 120. At the end of the breeding season, females in both groups
returned to high levels of LH, similar to those taken pretreatment (Fig. 1). The effect leuprolide
had on suppressing the formation of a corpus lutem were shown through comparisons between
progesterone levels in the treated deer verses the control group (Fig. 2). Progesterone levels in
the five leuprolide injected deer (group A) declined to nondetectable amounts at day 45 and
continuously stayed extremely low for the entire breeding season. In contrast, the control group
deer (group C) continually had much higher progesterone levels that treated deer up until day
150, which was reflective of a normal estrous cycle transitioning into a period of anestrus. This
test also showed evidence of reversibility because progesterone levels rose to around the original
pretreatment level by the time the next breeding season rolled around (Fig. 2). It was also found
that the GnRH agonist did not cause any health issues in the treated deer throughout the duration
of the study (Baker, Wild, Connor, Ravivarapu, Dunn, and Nett, 2004). The results of this study
are used as evidence that GnRH agonists, specifically leuprolide, were safely and effectively
used to manage the overpopulation of deer, and therefore have the potential for use in other
species.

CONCLUSION

Humane treatment of animals has become an increasingly popular topic of discussion in

today’s society. Public outcry over lethal culling has forced scientist and researchers to find a
more ethical way to control overpopulation of wildlife, especially in areas of increased human
development. The present review established that the use of fertility control agents or inhibitors,
specifically gonadotropin-releasing hormone agonists, have been increasingly used over the past
decade to more humanely control animal populations. The main reasons for amplified research
on this topic include increased understanding how molecules regulate fertility, innovative
technologies that make it easier for fertility control to be applicable with wild species, increased
animal welfare awareness through the use of the internet, and a growing demand to shut down
human-wildlife struggles (Massei and Cowan, 2014). The review emphasized how the use of
GnRH agonists is a safe and effective way to manage or inhibit fertility in wildlife, and how it
has successfully been achieved. However, more studies so far have fixated on marsupials,
rodents, and some carnivores to either reduce population expansion or decrease spread of
diseases. It has also been mentioned that even if fertility control methods succeed in decreasing
population levels that does not necessarily mean that the initial conflict has been fully resolved.
In order to use this in real human-wildlife conflict scenarios, further research is required to
determine if fertility control can truly solve the situation or only solve part of the problem
(Massei and Cowan, 2014). Lastly, even with the proven effectiveness of GnRH agonists, the use
of hormonal fertility control methods for wildlife is still disputed. This is because of the potential
for welfare issues including long-term effects, impacts within the environment, and even the
probability that steroids could be transferred from species to species through the food chain
(Nettles, 1997).

FIG URES

(Figure 1)
(Figure 2)
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