Steroid-induced urogenital tract changes and urine retention in laboratory rodents.

Since previous literature suggested that estrogen-treated male mice are models for human benign prostatic hypertrophy, a series of studies was designed to examine urine retention and urogenital tract changes in rodents given chronic estradiol-17 beta (E) and dihydrotestosterone (DHT) treatments. In Study 1, intact and castrate male mice received E, DHT or E plus DHT for four weeks via subcutaneous Silastic capsules. Bladder urine volume increased in the groups given E and this effect was not altered by castration, DHT or removal of E capsules two weeks before necropsy. Estrogen treatment also increased mortality. In Study 2, intact male, intact female, adrenalectomized (Adx) male and sham Adx male mice received 16 weeks of steroid treatments. Bladder urine volume increased in all E treated groups regardless of sex or Adx. Hydronephrosis, hydroureter and increased mortality were found in the E treated mice of both sexes. Estrogen induced epithelial changes and edema of the prostate, vas deferens and the utriculus prostaticus. In further studies male rats, hamsters and guinea pigs were given several different dosages of E but no evidence of urine retention or increased mortality was found. Taken together these studies suggest that E-induced urine retention is unique to mice. Although urine retention and hydronephrosis found in the mice were similar to those in humans with BPH, the lesion that results in the urine obstruction is not similar.

Prostacyclin (PGI2) effects on anterior pituitary hormones in the rat in vivo.

Intravenous injection of 600 microgram PGE2 or PGI2 significantly increased serum LH and prolactin levels in estradiol treated ovariectomized rats. There was no effect on serum FSH concentration. PGE2 and PGI2 stimulated LH release in a non-dose dependent manner, while prolactin levels were positively correlated with the dose administered following PGI2 treatment. 6-keto-PGF1 alpha at a comparable dose had no effect on pituitary hormone levels. Subcutaneous administration of 1 mg/kg or 60 mg/kg PGI2 for seven days significantly depressed serum LH level both in male and female rats. These doses had no effect on serum FSH or prolactin levels.

Serum FSH, LH and testosterone in the male rhesus following prostaglandin injection.

Adult male rhesus were treated with PGE2, PGF2 alpha or the 13,14-dihydro-15-keto metabolite of PGE2 in a randomized crossover design. Serum concentrations of FSH, LH and testosterone were determined and compared to the respective values in the same uninjected animals. No significant changes were noted in controls or following the metabolite injection. FSH increased gradually for 4 hours after metabolite treatment. In contrast, injection of PGF2 alpha was followed by an abrupt (within 15 minutes) increase in LH and testosterone. FSH increased gradually in 2 of 3 treated animals. Injection of PGE2 was followed by a similar abrupt increase in LH concentration. This was not always associated with a significant increase in testosterone or FSH. These results demonstrate that injections of PGE2 or PGF2 alpha can change serum gonadotropin and testosterone concentrations in male rhesus monkeys, and that the effects of these two prostaglandins are qualitatively different.

Effects of 15(S)-15-methyl prostaglandin F2 alpha methyl ester-containing silastic discs in male rats.

Silicone rubber discs containing 15(S)-15-methyl prostaglandin F2 alpha ester (15-Me-PGF2 alpha) in the matrix were implanted in the left side of the scrotums of Sprague-Dawley rats. The effect of 1% and 2% drug concentration was examined for 10, 20, or 28 days and compared with the effects of Silastic discs containing no prostaglandin. The discs containing prostaglandin reduced mean testicular and accessory gland weights. Histologically the testes and epididymides showed decreased or absent spermatogenic elements and hypertrophy of the interstitial cell masses in comparison with other cells. Implanted prostaglandin significantly depressed serum testosterone, luteinizing hormone, and follicle-stimulating hormone (FSH) concentrations when 15-Me-PGF2 alpha plasma concentrations exceeded 2 ng/ml. Hormone concentrations returned to control values as drug concentrations declined. FSH concentrations significantly exceeded control values 10 and 20 days after implantation, when prostaglandin concentration was nondetectable. The acute suppression of all three hormones suggest that 15-Me-PGF2 alpha either may act directly on the tests to suppress testosterone production or may suppress testosterone production or may suppress gonadotropin secretion, resulting in depressed testosterone output.

Fertility of male rats treated with 15(S)-15-methyl prostaglandin F2 alpha methyl ester-containing silastic implants.

Male Spraque-Dawley rats receiving implants of silicone rubber discs containing 1% or 2% 15(S)-15-methyl prostaglandin F2 alpha methyl ester (15-Me-PGF 2 alpha) or no prostaglandin were tested in successive breeding trials for potency and fertility. One week after implantation, discs containing 1% 15-Me-PGF2 alpha reduced potency and fertility, which returned 2 weeks after implantation. Animals receiving implants of the 2% discs were apparently impotent the 1st week following implantation; potency returned before full fertility returned 11 weeks after implantation.