Graduate Thesis Or Dissertation

 

Applications of GnRH Immunization in Domestic Dogs Public Deposited

Applications of GnRH immunization in domestic dogs

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/r781wk341

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  • Reproductive function in the dog is controlled by feedback mechanisms that involve the hypothalamus, the anterior pituitary gland, and the gonads. Surgical gonad removal, a common procedure performed in dogs for the purposes of sterilization, disrupts the hypothalamic-pituitary-gonadal (HPG) axis and results in permanently elevated concentrations of gonadotropins. Manipulation of the HPG axis via gonadotropin releasing hormone (GnRH) immunization results in the synthesis of GnRH neutralizing antibodies, which bind to (neutralize) GnRH and prevent it from binding to its receptors. The end result of GnRH immunization is the cessation of pituitary gonadotropin secretion, namely luteinizing hormone (LH). In 2004, a commercial GnRH vaccine was launched in the United States (Canine Gonadotropin Releasing Factor Immunotherapeutic®; Pfizer Animal Health USA), labeled for the treatment of benign prostatic hyperplasia in intact male dogs. This research investigated two novel clinical applications of this vaccine in dogs. In the first study, physiologic responses to GnRH immunization in intact male dogs were observed. Four intact males were vaccinated with the GnRH vaccine twice at four week intervals. Blood samples were collected prior to each injection (at weeks 0 and 4) and at weeks 12 and 20 following initial vaccination. Scrotal measurements were also made at the time of each blood sample collection to calculate testicular volume. All four dogs developed a GnRH antibody titer and experienced a significant decrease in testosterone concentrations. Testicular volume also significantly decreased, and this effect was reversed by the end of the study. LH concentrations remained at basal levels. These results are indicative of temporary humoral response to the GnRH vaccine, and future studies should investigate prolonging these effects to potentiate GnRH immunization as a method of population control in dogs. Beyond use as a temporary immunosterilant, GnRH immunization has other promising clinical applications. Elevated gonadotropin concentrations as a result of gonad removal in female dogs decreases urethral pressure, and in some bitches, this results in the development of urethral sphincter mechanism incompetence (USMI). Therefore, lowering gonadotropin concentrations in incontinent ovariectomized bitches through GnRH immunization may restore continence. In the second study, sixteen incontinent dogs that were using phenylpropanolamine (PPA) to control incontinence were recruited. Eleven dogs were immunized against GnRH at week 0, and nine dogs were vaccinated again four weeks later. Five control dogs were vaccinated with a placebo twice at four week intervals. Vaccinated dogs discontinued PPA two weeks after re-vaccination, and control dogs remained on PPA for the duration of the study. Blood samples were collected before each injection and at 6, 8, 10, 12, 16, 20, and 24 weeks, and owners recorded episodes of incontinence throughout the study. Of the nine dogs that completed the vaccination series, four dogs remained continent after PPA was discontinued. For these four dogs, there was no difference in the episodes of incontinence when using PPA versus treatment with the vaccine. All nine vaccinated dogs developed a GnRH antibody titer, and LH concentrations decreased significantly in vaccinated dogs compared to controls. These results indicate that decreasing LH concentrations through GnRH immunization restores continence to some, but not all incontinent ovariectomized bitches. Because the development of USMI results from decreased urethral pressure that happens after ovariectomy, future studies should focus on preventing this decrease in urethral pressure to prevent USMI from occurring.
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