Some characteristics of the uterine progestorone receptor and the effects of norethindrone on conception in the rock hyrax (Procavia capensis)

Abstract

The mean dissociation constant (± SEM) of the uterine progesterone receptor for progesterone in eight rock hyraxes, culled at Elandsrand Mine Reserve, was 1.78 nM (±O.l07). The receptor also showed a high relative binding affinity (RBA) for the synthetic hormones norethindrone (%RBA = 185), levonorgestrel (%RBA = 179) and RU486 (%RBA = 221). The binding of norethindrone is similar to that of the African elephant and thus allows for the use of the hyrax as a biological model for the development of a contraceptive for the elephant as an alternative to elephant culling. Norethindrone and cholesterol (placebo) implants in 18 captive hyraxes resulted in zero pregnancies for the seven animals receiving norethindrone, five pregnancies in the eight animals receiving cholesterol and three pregnancies in the three animals receiving no implants. Circulating oestradiol-17Â and progesterone concentrations of the mid-pregnant and non-pregnant animals were similar to those in free ranging hyraxes, suggesting that norethindrone had no effect on the availability of these hormones. Histological investigation of selected organs (adrenals, liver, spleen, uterus and ovaries) showed that the effects of norethindrone were limited to the endometrial and ovarian tissue. The endometrium showed atrophic glands and proliferating stromal cells while the ovaries were inactivated. This indicated that norethindrone possibly interferes with both the uterine environment and ovulation, thus preventing conception. This study indicates that norethindrone has contraceptive abilities in the rock hyrax that can potentially be extrapolated to the African elephant, in the search for a contraceptive to manage high population growth rates.