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Transmission of relaxin and estrogens to suckling canine pups via milk and possible association with hip joint laxity

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  • 1 Nelson Institute of Environmental Medicine, School of Medicine, New York University, Tuxedo, NY 10987.
  • | 2 Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 3 Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 4 Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.
  • | 5 Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425.
  • | 6 Department of Obstetrics, Gynecology and Women's Health, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103.

Abstract

Objective—To determine whether abnormal laxity of hip joints of canine pups with genetic predisposition to hip dysplasia (HD+) is related to ingestion of milk-borne hormones.

Animals—7 female Labrador Retrievers with HD+ and 8 with low predisposition to hip dysplasia (HD–) and their offspring.

Procedures—Immunoactive relaxin, estrogen, and estrogen precursor concentrations in milk of HD+ lactating bitches and in serum of their pups were compared with those of HD– bitches and pups. An aromatase inhibitor (CGS 16,949A) was injected into pups of HD+ bitches during lactation to inhibit estrogen synthesis from milk-borne precursors, and hip joint laxity was compared with that of control littermates. Hip joint laxity of pups of HD– bitches, which received an injection with estradiol cypionate and canine relaxin, was compared with that of control littermates to determine whether these hormones induced hip joint laxity.

Results—High concentrations of estrogens and relaxin were found in milk of HD+ and HD– bitches throughout lactation. Serum concentrations of milk-derived relaxin and total estrogens were similar in all pups, but estradiol-17B was detected only in pups of HD+ bitches. Hip joint laxity was reduced in pups that received CGS 16,949A. Hip joint laxity was increased in pups of HD– bitches that received estradiol cypionate and relaxin.

Conclusions and Clinical Relevance—Milk-borne maternal hormones and precursors were absorbed into the circulation of canine neonates and may play a role in hip joint laxity in HD+ pups. Phenotypic expression of hip dysplasia may therefore be preventable by antihormone treatment.

Contributor Notes

Supported by Public Health Service Grant RO1 HD30721-003, Morris Animal Foundation 87CA-22, and March of Dimes Birth Defects Foundation Grant #1-FY96-1086 and in part by National Institute of Environmental Health Sciences Center Grant P30 ES000260 and National Cancer Institute Center Grant P30 CA016087.

The authors thank Carla Randolph, Sally Lasano, and Andrea Wojtczuk for technical assistance and Dr. Ronald Steele of the Novartis Corp for the generous donation of CGS 16,949A.

Address correspondence to Dr. Steinetz.