ABSTRACT
Male dogs and cats were immunized against LHRH in order to evaluate the feasibility of an immunological approach to pet
contraception. In the first study, dogs were immunized with 100, 500, or 2500 fIg of LHRH conjugated to tetanus toxoid. A
significant decline in serum testosterone (T) levels was observed in all immunized dogs, reaching castration levels in some animals
by Week 4 and remaining suppressed in all the immunized dogs through the course of the study. Testicular histology suggested
arrest of spermatogenesis (infertility). The effects of "immunological castration" were reversible (study 2): steroidogenesis suppressed
by "immunological castration" was restored as antibody titers declined. Effective antibodies were rapidly reinduced in
dogs by a single injection of LHRH,-TT. In contrast, the level of antibodies induced in male cats (study 3) was not sufficient for
"immunological castration."
The conclusion was that active immunization against LHRH could provide a cost-effective, nonsurgical, reversible means to
control the fertility of companion animals.
INTRODUCTION
Pet overpopulation is one of the most serious problems
in the field of animal protection. Nationally, animal shelters
must destroy more than 5 million unwanted dogs and cats
each year (The American Society for the Prevention of Cruelty
to Animals).
Presently, spaying and neutering are the most practical
methods available to control pet reproduction as well as
undesirable sexual behavior (spraying, mounting, vocalizing,
aggression). Factors of cost and irreversibility make these
surgical methods difficult to implement, creating a need for
low-cost alternatives. Low-cost methods of humane fertility
control may become available through research directed at
hormones of the reproductive system.
LHRH is a decapeptide produced by the hypothalamus.
LHRH acts as the master reproductive hormone through
regulation of the release of LH and FSH from the pituitary
[1]. In males, LH regulates testosterone (T) synthesis; FSH
is necessary for the initiation and maintenance of spermatogenesis
[2, 3]. T is needed for spermatogenesis and for
the development of secondary sexual characteristics including
behavioral characteristics such as territorial marking
(spraying), mounting, and aggressiveness. In females,
both LH and FSH are required to stimulate the ovarian
changes leading to ovulation [4]. In early studies aimed at
raising antisera against LHRH, in which high antibody titers
were achieved in male rabbits, the testes became atrophied
[5]. Since then, it has been shown that inducing sufficient
Accepted August 10, 1994.
Received April 11, 1994.
'Research was conducted with support of a grant from Geraldine R Dodge Foundation.
2Correspondence: Dr. Anna Ladd, Vaccine Research, Inc., 148 Neptune Avenue,
Brooklyn, NY 11235.
levels of antibodies against LHRH leads to the suppression
of reproductive behavior in both males and females, the
suppression of synthesis and secretion of gonadotropins and
gonadal steroid hormones, gonadal atrophy, and arrest of
gametogenesis [6]. These observations suggested the potential
application of immunization against LHRH for the
regulation of gonadal functions and fertility in domestic animals
[7, 8] and humans [9, 10].
The studies reported here were conducted in male dogs
and cats. Only pharmaceutically acceptable materials were
used in all studies.
MATERIALS AND METHODS
Animals
Study 1 was conducted in male dogs at White Eagle Laboratories
(Doyles Town, PA), a facility licensed by the Food
and Drug Administration for conducting studies in accordance
with regulations for Good Laboratory Practice. Dogs
were maintained in accordance with USDA regulations for
the care and use of laboratory animals. Other experiments
in dogs and the studies in cats were conducted at the Laboratory
Animal Research Center at the Rockefeller University.
This facility is fully accredited by the American Association
for the Accreditation of Laboratory Animal Care. All
experiments were approved by Institutional Animal Care
and Use Committees. Animals were injected subcutaneously
(s.c.) at the designated time points (see Experimental
Design). Two to three milliliters of blood was collected from
the jugular vein (cats) or median cubital vein (dogs). Testicular
sizes (study 1) were obtained by measuring length
and width of testicles with a caliper at the times of blood
collection. Thin-needle testicular biopsy (study 1) was performed
at White Eagle Laboratories by the attending veterinarian
20 wk after the initial immunization.
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