E. A. Thorndike and A. S. Turner

Department of Clinical Sciences, Colorado State University, Ft.Collins ,CO 80523

Received 9/25/97 Accepted 4/10/98

8. PERSPECTIVE

Coronary artery disease, osteoporosis, osteoarthritis and oral bone loss can occur after menopause and all have a major impact on women’s health. It is premature to promote the sheep as a model to study estrogen deficiency; the many differences from small animal omnivores and non-human primates need to be overcome. Specifically, there is a need to validate the aged OVX ewe as a model for CAD. Although dietary fat has a depressive effect on rumen fermentation (60), it would be of interest to feed sheep modified dietary fat, (encapsulated or as calcium soaps, which are utilized to avoid desaturation within the rumen bacteria) to OVX ewes and then search for atherogenic changes.

Female sex steroids have also been shown to affect the composition and structure of many tissues other than the reproductive organs. Recently, estrogen and progesterone receptors were identified in synoviocytes in the synovial lining, in fibroblasts in the anterior cruciate ligament stroma, and in the cells in the blood vessel walls of the ligament (61). Demonstration of sex hormone receptors in these tissues suggests that future studies using animal models could provide further answers to a variety of other orthopaedic conditions associated with menopause.

Clinical and epidemiological studies have suggested a protective (or an onset-delaying) affect of estrogen against Alzheimer’s disease (AD) (62-64). Findings imply that estrogen may also protect cognitive functions associated with aging. Further, estrogen replacement therapy may protect against memory decline in nondemented postmeniopausal women and has a beneficial role on cognitive functioning (65). Additional studies of the neurobiological mechanisms for ERT in large animals may help characterize AD well before the diagnosis of the disease.

A series of questions remain unanswered until estrogen-deficient sheep have been studied more intensively: (1) Do the various breeds of sheep differ in their response to estrogen deficiency? (2) What is the effect of parity on bone loss associated with estrogen deficiency? (3) Should OVX be performed during anestrus, prior to regular estrus cycles or when regular estrus cycles are occurring? (4) Is climate (exposure to sunlight) a factor? (5) Can physiological measurements (e.g. core body temperature) for hot flashes be developed in this model?

As the financial climate in biomedical research continues to deteriorate, the search for more economical models must continue. One step is to network or collaborate with other researchers interested in similar models or conditions. In our laboratory for instance, a group of OVX ewes, a control group (sham) and treatment groups can provide specimens for those interested in CAD, osteoporosis, OA, and oral bone loss, as well as other diseases. The skeletally mature OVX ewe therefore offers the opportunity to study the pathophysiology of the postmenopausal diseases and research on new therapeutic agents.