cyproterone and Hypertension

Topics: Aminopropionitrile; Androgens; Animals; Arteriosclerosis; Blood Vessels; Cell Differentiation; Cholesterol; Collagen; Cyproterone; Elastin; Estrogens; Glycosaminoglycans; Humans; Hyperlipidemias; Hypertension; Muscle, Smooth; Rabbits; Rats

In the syndrome of familial virilization, insulin resistance, and acanthosis nigricans, the interrelationships are not understood. Twin sisters were studied, along with a lesser affected sister and mother. They manifested amenorrhea, hirsutism, masculinization, hypertension, hyperinsulinemia, hypertriglyceridemia, and hyperprolactinemia. Medical therapy with a gonadotropin-releasing hormone agonist plus an antiandrogen resulted in reversal of the hirsutism, yet with preservation of potential fertility. In response to luteinizing hormone (LH) and follicle-stimulating hormone suppression, there was normalization of the serum androgens, but not of the hyperinsulinemia, hypertriglyceridemia, hyperprolactinemia, hypertension, or acanthosis nigricans.. (1) This syndrome may be familial. (2) Medical therapy for the virilization is successful. (3) The hyperandrogenemia is primarily LH dependent and not primarily insulin dependent, although insulin may have an amplification effect. (4) Hyperinsulinemia, hypertriglyceridemia, hyperprolactinemia, and the hypertension are not androgen dependent.

Topics: Acanthosis Nigricans; Adult; Androgen Antagonists; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Dexamethasone; Diseases in Twins; Family Health; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hirsutism; Humans; Hyperinsulinism; Hyperlipidemias; Hyperprolactinemia; Hypertension; Insulin Resistance; Leuprolide; Luteinizing Hormone; Male; Pituitary Hormone-Releasing Hormones; Syndrome; Virilism

Spirolactones are aldosterone antagonists which inhibit the binding of aldosterone to the renal mineralocorticoid receptor. These molecules also possess an antiandrogenic effect which could be due, among other possibilities, to a peripheral antagonism of androgens. This hypothesis has been tested in the present study. From in vivo experiments, spironolactone K+ canrenoate appear to inhibit the binding of [3H]5alpha-dihydrotestosterone [3H]DHT to the cytosolic and nuclear receptor of the rat ventral prostate. The doses used are in the same range as those used for demonstrating the antimineralocorticoid effect of these molecules. In vitro incubations and in vitro displacement studies show that spironolactone and K+ canrenoate are respectively about 20 and 100 times less effective than DHT in displacing 50 percent of 5 times 10- minus 10 M [3H]DHT from its receptor. Spirolactones are also able to compete with [3H]DHT for the specific 8 S cytosolic receptor. Neither spironolactone nor K+ canrenoate decreases prostatic 5alpha-reductase activity, even at a concentration as high as 10- minus 5 M. It seems likely that spirolactones, besides their action on testosterone biosynthesis, exert their antiandrogenic activity via a peripheral androgen antagonism.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Animals; Binding, Competitive; Canrenoic Acid; Cell Nucleus; Cyproterone; Cytosol; Dihydrotestosterone; Hyperaldosteronism; Hypertension; Male; Prostate; Rats; Receptors, Cell Surface; Spironolactone; Tritium

Topics: Androgen Antagonists; Androstanes; Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Castration; Collagen; Cyproterone; Elastin; Hypertension; Male; Muscle, Smooth; Organ Size; Proteins; Rats