Effects Of Chlormadinone Acetate Research Articles

The effects of chlormadinone acetate (CMA), antiandrogen, on the pituitary, testis, prostate and adrenal gland of the dog with spontaneous benign prostatic hyperplasia.

The effect of chlormadinone acetate (CMA), a synthetic steroidal antiandrogen, on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Male beagle dogs (5-8 years old) were divided into four experimental group. Group 1 consisted of untreated controls. Groups 2 and 3 received CMA 0.03 and 0.1 mg/kg/day, p.o., respectively, for 6 months. In group 1, glandular hyperplasia of the prostate was clearly detected. The glandular epithelial cells showed uniformly intense nuclear staining for androgen receptor (AR). AR was also localized in the nuclei of the fibro-muscular stromal cells. In groups 2 and 3, CMA produced marked atrophy of the glandular epithelium. The interacinar fibro-muscular stroma was prominent. The nuclear staining for AR in both epithelial and stromal cells was remarkably decreased. In addition, a histopathological study showed that CMA medication for 6 months exerted no effect on the testes and adrenal glands or on immunoreactive positive cells to LH- and ACTH-antibody (pituitary LH- and ACTH-cells). Therefore, it is concluded that CMA (0.03 and 0.1 mg/kg) causes regression of spontaneous canine BPH without any histopathological effects on the testes, adrenal glands or pituitary LH- and ACTH-cells.

Effects of chlormadinone acetate and ethinylestradiol treatment on epididymal 5 alpha-reductase activities in patients with prostate cancer.

The difference between in vivo and in vitro inhibitory effects on epididymal 5 alpha-reductase was investigated by using epididymides obtained from patients treated with chlormadinone acetate (6-chloro-3,20-dioxo-4,6-pregnadien-17-yl acetate, CMA) or ethinylestradiol (17 alpha-ethynyl-1,3,5(10)-estratriene-3,17 beta-diol, EE2). In the in vitro study CMA exhibited competitive inhibition, whereas EE2 was a noncompetitive inhibitor of human epididymal 5 alpha-reductase. Their in vitro inhibitory effects were weak compared with the effect of finasteride ((-)-N-tert-butyl-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta carboxamide), a steroidal 5 alpha-reductase inhibitor. The Ki values of CMA, EE2, and finasteride were 1.4 x 10(-5) M, 1.5 x 10(-5) M, and 1.3 x 10(-9) M, respectively. Despite their weak in vitro inhibitory potency, CMA and EE2 strongly inhibited testosterone 5 alpha-reductase in vivo. There were regional differences in inhibitions by CMA and EE2 on human epididymal 5 alpha-reductase activity depending on the site of the epididymis; the efferent ductules, the head, the body or the tail. In vivo administration of CMA reduced epididymal 5 alpha-reductase activity by 49.7% to 89.4%. In vivo administration of EE2 reduced epididymal 5 alpha-reductase activity by 82.7% to 96.3%. The apparent Km values for the enzyme in patients treated with CMA or EE2 and untreated patients did not differ significantly. The Vmax values were significantly decreased in treated patients. These findings suggest that the marked in vivo inhibition of 5 alpha-reductase induced by CMA and EE2 was not related to the direct action of these compounds, but resulted from a reduction in the amount of the enzyme.

Effects of low doses of chlormadinone acetate in the rat.

The effects of chlormadinone acetate (CA) administered im in doses of .2-1 mb/day for 40 days on the reproductive organs and pituitary gland of the rat were studied. The .2 mg/day regimen did not produce changes markedly different from control values. However as the dosage increased there was a parallel decrease in the weights of the testis accessory sex organs and the pituitary. Pituitary gonadotropin function and the fructose content of the coagulating gland also decreased while testicular levels of cholesterol increased. Spermatogenesis was arrested in animals receiving .5 or 1 mg/day CA and no spermatozoa were observed in the epididymis of these animals. Immotile spermatozoa were found in the epididymides of rats receiving .2 mg/day. The results indicate that CA is capable of selectively hindering epididymal function and maturation of spermatozoa at low doses without markedly altering pituitary gonadotropin secretion or testicular function.

The effects of chlormadinone acetate upon estradiol uptake by the rat mammary gland in organ culture

Chlormadinone acetate (CAP) was found to inhibit the uptake of 3H-estradiol-17β (E2) by rat mammary glands in organ culture when 3H-E2 was added simultaneously with CAP, suggesting that CAP may act as an antiestrogen by competing with E2 for the binding sites. However, when CAP was added 24 hours before 3H-E2, uptake was increased. These results suggest a mechanism by which CAP may, by enhancing the binding of E2 in the mammary gland, exert estrogenic action.

Effects of chlormadinone acetate (Estrostat) on preweaning and postweaning growth rate and breeding efficiency of beef heifers.

Effects of chlormadinone acetate (Estrostat) on preweaning and postweaning growth rate and breeding efficiency of beef heifers.

The action of chlormadinone acetate (6-chloro-delta6-dehydro-17alpha-acetoxyprogesterone) upon experimentally induced ovulation in the rabbit.

1. The ovulation response to electrical stimulation of the median eminence, or to the intrapituitary infusion of median eminence extract, was observed in control rabbits and animals pre-treated with chlormadinone acetate.2. Chlormadinone acetate pre-treatment did not significantly reduce the proportion of rabbits ovulating in response to electrical stimulation. However, there was a significant reduction in the average number of ruptured follicles when compared with the animals in the control group.3. Chlormadinone acetate pre-treatment significantly reduced the proportion of animals ovulating in response to the intrapituitary infusion of median eminence extract as compared with the control series. However, there was no significant reduction in the average number of ruptured follicles (in those rabbits that ovulated) when compared with the control groups.4. Chlormadinone acetate pre-treatment produced no significant effect upon either the proportion of animals ovulating, or the average number of ruptured follicles, following I.V. injection of 50 mug LH.5. The conclusion drawn is that chlormadinone acetate blocks copulattion-induced ovulation in the rabbit by action at a site in the central nervous system located above the median eminence. The possible effects of chlormadinone acetate upon the secretion of FSH, the pituitary sensitivity to releasing factors and the ovarian sensitivity to LH are discussed.