National Wildlife Research Center (NWRC)

Development of Injectable and Oral Contraceptive Technologies and Their Assessment for Wildlife Population and Disease Management

Gonadotropin-Releasing Hormone Immunocontraception in Mammals

Control of Reproduction by GnRH

(NWRC publications on GnRH)

Gonadotropin-releasing hormone, which is produced in the hypothalamus at the base of the brain, controls the release of the pituitary gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone). These gonadotropins regulate hormones that drive sperm production in males and follicular development and ovulation in females. Excitation of the GnRH neurons results in the release of stored GnRH peptide from its secretory granules in the hypothalamus. After it diffuses into the surrounding capillary blood, the GnRH travels via the hypophysial portal system to the anterior pituitary, where it diffuses from the capillaries and binds to and activates the LH and FSH gonadotrophs. This activation causes the release of stored gonadotropins, which diffuse back through the capillaries into the bloodstream. The gonadotropins then travel to and activate the reproductive organs, resulting in steroid synthesis and normal sexual activity.

GnRH Immunocontraception

The GnRH vaccine stimulates the production and release of GnRH-specific antibody from the B-cell into the bloodsteam. The antibody circulates throughout the body, and when it reaches the capillary region of the hypothalamus, it comes into contact with GnRH that has diffused into the capillaries after being produced in the hypothalamus. Binding of GnRH to the specific antibody forms large immune-complexes that travel down the hypophysial stalk. Because of their large size, however, the immune-complexes are unable to diffuse out of the blood at the pituitary capillaries. Instead, they remain in the venous blood and leave the pituitary without stimulating the release of LH and FSH. Without the LH and FSH that normally stimulate the synthesis of steroids in the reproductive organs, animals of both sexes remain in an asexual, non-reproductive state. As long as there is sufficient antibody to bind all GnRH circulating in the hypothalamic/pituitary portal system, all sexual activity will be suspended and animals will remain non-reproductive.

Diagram of gonadotropins pathway untreated with GonaCon.
Diagram of gonadotropins pathway treated with GonaCon.

Project Home Page
Project Goals and Objectives
Accomplishments
Publications
GonaCon™
GnRH Immunocontraception (Technical Discussion)
Adjuvant Development (Technical Discussion)
Conjugate Design (Technical Discussion)
Nicarbazin
Diazacon
PZP