The Nuclear Uptake and Retention of a Synthetic Progestin in the Cardiovascular System of the Baboon*

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Abstract
There is a sexual dimorphism in the incidence of coronary heart disease. This observation, together with more recent reports of increased cardiovascular disease associated with the use of oral contraceptives, led to a search for steroid receptors in the cardiovascular system. The nuclear uptake and retention of a synthetic progestin in the cardiovascular system of the baboons was examined. Long term oophorectomized baboons were primed with estradiol benzoate for 3 days before the experiment (50 .mu.g/kg, i.m.) and adrenalectomized 2 days before the experiment. On the day of the experiment, the animals were injected under anesthesia with 2.5 .mu.g/kg body wt (3H)ORG 2058 (16.alpha.-ethyl-21-hydroxy-19-nor-[6,7-3H]pregn-4-ene-3,20-dione) or with (3H) ORG 2058 plus a 1000-fold excess of unlabeled progesterone (control). ONe after the injection, the animals were rapidly exsanguinated, and parts of the cardiovascular system were removed and processed for autoradiography. Localization of the synthetic progestin was found in nuclei of between 25-75% of all smooth muscle cells of the media of all arteries examined and to a lesser extent in the nuclei of the fibroblasts and other cells of the adventitia. Localization of the synthetic progestin in the heart was limited to .apprx. 1% of the myocardial cells and < 5% of interstitial cell nuclei. The pattern of localization found differs from that for estrogen and androgen and suggests the possible presence of estrogen-independent progesterone receptors in smooth muscle cells of the media of the aorta and coronary arteries.

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