Modulation of ovarian function in female dogs immunized with bovine luteinizing hormone receptor.
Adult female dogs were immunized with 0.5 mg bovine luteinizing hormone receptor (LH-R) encapsulated in a silastic subdermal implant and subsequently with four intramuscular booster injections of 0.1 mg LH-R each. Circulating LH-R antibody was detected in the sera 3 weeks post-implant. The appearance of LH-R antibody was associated with a decline in the serum progesterone concentrations to a range of 0-0.5 ng/ml until day 365 in the immunized dogs in comparison with a range of 5-10 ng in the control animals, suggesting a lack of ovulation and corpus luteum function in immunized dogs. The immunized dogs did not show signs of 'standing heat' and failed to ovulate when induced by LH-RH challenge. Serum oestradiol levels, however, remained in the range of 30-40 pg/ml in both the immunized and the control dogs. With the decline in the antibody titres, the hormonal profile and vaginal cytology returned to a fertile state and the dogs exhibited signs of 'standing heat', as well as vaginal bleeding. Dogs immunized with LH-R did not show any serious metabolic, local or systemic adverse effects. The hypothalamic--pituitary gonadal axis remained intact as indicated by little difference in pituitary LH levels between control and immunized animals, and by the release of LH by LH-RH challenge. These studies demonstrate that active immunization of female dogs with LH-R could immunomodulate ovarian function to cause a reversible state of infertility. It may be postulated that, due to extensive interspecies homology, a recombinant LH receptor-based immunocontraceptive vaccine may also be effective in other vertebrates.
Saxena
B B
BB
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Weill Medical College of Cornell University, New York, USA.
Clavio
A
A
Singh
M
M
Rathnam
P
P
Bukharovich
Y
Y
Reimers
T
T
Saxena
A
A
Perkins
Scott
S
D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000097:blood; D003338:Corpus Luteum / Q000276:immunology; D004285:Dogs / Q000097:blood / Q000276:immunology / Q000502:physiology*; D004343:Drug Implants; D004958:Estradiol / Q000097:blood; D005260:Female; D007987:Gonadotropin-Releasing Hormone; D007114:Immunization / Q000662:veterinary; D007273:Injections, Intramuscular / Q000662:veterinary; D007986:Luteinizing Hormone / Q000097:blood; D010053:Ovary / Q000276:immunology / Q000502:physiology*; D010060:Ovulation / Q000276:immunology* / Q000502:physiology; D011374:Progesterone / Q000097:blood*; D011974:Receptors, LH / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D004343:Drug Implants; D011974:Receptors, LH; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone