Sex hormone regulation of collagen concentrations in cranial cruciate ligaments of sexually immature male rabbits

Victoria A. Light Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

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Ron D. Montgomery Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

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Benson T. Akingbemi Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

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Abstract

Objective—To investigate the effects of gonadectomy on collagen homeostasis in cranial cruciate ligaments of male rabbits.

Animals—30 sexually immature (16-week-old) male New Zealand White rabbits.

Procedures—Rabbits were randomly assigned to 5 groups of 6 rabbits each: sexually intact, placebo (control group); castrated, placebo; castrated, testosterone; castrated, dihydrotestosterone; and castrated, 17β-estradiol (E2). Control rabbits underwent a sham operation, and all other rabbits underwent gonadectomy. At the time of gonadectomy, the placebo and sex hormones were administered via slow-release pellets implanted subcutaneously as assigned. After 21 days of hormone supplementation, measurements were obtained of serum testosterone and E2 concentrations, ligament collagen characteristics, and androgen receptor, estrogen receoptor α, and matrix metalloproteinase expression.

Results—Following gonadectomy and hormone supplementation, the treatment groups differed in serum testosterone and E2 concentrations to various degrees. Collagen concentrations were lower and fiber diameters higher in the absence of sex hormones, in association with the degrees of estrogen receptor a and androgen receptor expression. Although differences were detected among the groups in matrix metalloproteinase expression, these differences were not significant.

Conclusions and Clinical Relevance—Sex hormones appeared to play a role in cranial cruciate ligament homeostasis in male rabbits. Physiologic changes triggered by the lack of sex hormones following gonadectomy in sexually immature rabbits may potentially predispose those rabbits to orthopedic injuries.

Abstract

Objective—To investigate the effects of gonadectomy on collagen homeostasis in cranial cruciate ligaments of male rabbits.

Animals—30 sexually immature (16-week-old) male New Zealand White rabbits.

Procedures—Rabbits were randomly assigned to 5 groups of 6 rabbits each: sexually intact, placebo (control group); castrated, placebo; castrated, testosterone; castrated, dihydrotestosterone; and castrated, 17β-estradiol (E2). Control rabbits underwent a sham operation, and all other rabbits underwent gonadectomy. At the time of gonadectomy, the placebo and sex hormones were administered via slow-release pellets implanted subcutaneously as assigned. After 21 days of hormone supplementation, measurements were obtained of serum testosterone and E2 concentrations, ligament collagen characteristics, and androgen receptor, estrogen receoptor α, and matrix metalloproteinase expression.

Results—Following gonadectomy and hormone supplementation, the treatment groups differed in serum testosterone and E2 concentrations to various degrees. Collagen concentrations were lower and fiber diameters higher in the absence of sex hormones, in association with the degrees of estrogen receptor a and androgen receptor expression. Although differences were detected among the groups in matrix metalloproteinase expression, these differences were not significant.

Conclusions and Clinical Relevance—Sex hormones appeared to play a role in cranial cruciate ligament homeostasis in male rabbits. Physiologic changes triggered by the lack of sex hormones following gonadectomy in sexually immature rabbits may potentially predispose those rabbits to orthopedic injuries.

Contributor Notes

This manuscript represents a portion of a dissertation submitted by the first author to the Auburn University College of Veterinary Medicine as partial fulfillment of the requirements for a Doctor of Philosophy degree.

Supported by a Scott-Ritchey Research Center (SRRC) Interdepartmental Research Grant Program award to Dr. Akingbemi.

The authors thank Karen Wolfe for technical assistance.

Address correspondence to Dr. Light (lightva@tigermail.auburn.edu) or Dr. Akingbemi (akingbt@auburn.edu).
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