Testosterone Production In Rats Research Articles

The Effect of a 5α-Reductase Inhibitor on Androgen Physiology in the Immature Male Rat*

To provide insight into the role of 5 alpha-dihydrotestosterone (DHT) in postnatal androgen physiology, we administered the 5 alpha-reductase inhibitor finasteride to male rats from birth through the onset of puberty. In 4-week-old control rats serum testosterone levels averaged 0.21 ng/ml, and DHT levels averaged 0.64 ng/ml. By 7 weeks of age, testosterone levels increased more than 7-fold to 1.57 ng/ml, while the circulating DHT level declined to 0.26 ng/ml. In both the 4- and 7-week-old inhibitor-treated animals, circulating DHT levels were 25-50% of control values, and circulating testosterone levels were higher than control values. In 7-week-old inhibitor-treated rats, the weights of prostate, penis, seminal vesicles, and epididymal tissues were only 30-50% those of the controls. However, DHT formation is apparently not critical for postnatal development of the preputial glands or the androgen-dependent perineal muscles, since the weights of these tissues were not affected by treatment with inhibitor. Treatment with the 5 alpha-reductase inhibitor had no apparent effect on testicular histology or daily sperm production despite the fact that testicular DHT content was lower (70%) and testosterone content was higher (250%) than those in controls. We conclude that DHT formation is important for the normal postnatal growth of the prostate, seminal vesicles, epididymis, and penis and may be important for normal feedback control of testosterone production in rats, but that its formation is not critical for the onset of spermatogenesis or the development of the preputial glands or the androgen-dependent perineal muscles.

Relationships between plasma progesterone levels and testicular testosterone production in the rat fetus: effects of maternal ovariectomy.

The present study was performed to examine whether circulating progesterone regulates testicular testosterone production in the fetal rat. Progesterone levels in fetal plasma were found to increase from day 14.5 to day 16.5; thereafter they reached a plateau between days 16.5 and 18.5 (80 nmol/l) and decreased threefold between days 18.5 and 21.5. The addition of progesterone, within the range of normal plasma concentrations, induced a dose-dependent increase in testosterone produced in vitro by the testes on days 16.5 and 18.5 but not on day 20.5. However, in 18.5-day-old fetuses, individual plasma progesterone levels were not correlated with testicular testosterone production in vivo and in vitro. Furthermore, maternal bilateral ovariectomy induced a significant fall in plasma progesterone in 18.5-day-old fetuses; this was not associated with a reduction in plasma testosterone nor in testicular testosterone content, although the amount of testosterone secreted by the testis incubated in vitro was slightly but significantly reduced. It is concluded that circulating progesterone does not regulate testicular testosterone production in vivo although the testis may use plasma progesterone as a substrate. On day 18.5 after maternal ovariectomy, the decrease in plasma progesterone levels was similar in fetuses and mothers, suggesting that most fetal progesterone originates from maternal plasma.

Effect of gossypol on testicular blood flow and testosterone production in rats.

Rats were treated with highly purified gossypol acetic acid at doses of 15 or 30 mg/kg day-1 for 6 weeks to produce an effect on spermatogenesis as shown by reduced sperm motility and increased sperm malformation rates. The treated rats did not differ from the controls in the body weight growth curves and reproductive organ weights. When stimulated with hCG, testicular blood flow was increased in the low dose group; the testosterone concentrations in peripheral and testicular venous blood were also increased to a greater extent than those of the control group. No difference was found between the high dose and control groups in testicular blood flow or testosterone concentrations. The morphology of the Leydig cells was apparently normal, although some degenerative changes in the germinal epithelium were observed in the high dose group. Therefore, there is no evidence in our experiment to show any anti-androgenic effect following 6-week treatment of gossypol in rats, even at the dose of 30 mg/kg day-1.

Effect of Anesthetics on Testosterone Production in Rats

Changes in testicular vein and peripheral testosterone concentrations in mature rats were monitored during anesthesia with six different agents. Samples taken 2–3 minutes after initial disturbance of the resting animal yielded mean testicular vein testosterone levels of 59–247 ng/ml plasma in nine separate groups of rats. Sustained anesthesia under halothane, enflurane, pentobarbital, ether, urethan, or ketamine/promazine resulted in a decline in testicular vein testosterone to 10–60 ng/ml by the third hour. Luteinizing hormone levels, measured under enflurane anesthesia, also fell significantly by 1 and 2 hours after administration of anesthesia, although follicle‐stimulating hormone remained constant. Testes of the enflurane‐anesthetized rat were still able to respond to gonadotropins, but withdrawal of the anesthetic did not reverse the downward trend in testosterone. No changes in testicular blood flow were detected during anesthesia, although flow under urethan anesthesia was consistently slower than with other agents. The first 90 minutes of urethan anesthesia were characterized by severe fluctuations in testicular vein testosterone. Halothane, enflurane, and pentobarbital resulted in a larger ratio of peripheral to testicular vein testosterone compared with ether or rapid sampling, suggesting a reduction in turnover rate under these three agents. Conclusions were that different anesthetic agents can distort hormone levels and endocrine function of the testes in various ways, and that the production rate of testosterone by rat testes is higher than has been previously suggested.

The effect of estrogens on luteinizing hormone plasma levels and on testosterone production in intact and hypophysectomized rats.

Intact male rats were injected with 50 μg E2B (estradiol benzoate) or with 100 μg E2 (estradiol). Six hours after injection plasma and testicular testosterone levels and production were significantly decreased. Concomitant with this change lowered LH plasma levels could be observed in the estrogentreated animals. Twenty-four hours after injection of 50 μg E2B LH levels, testosterone levels and testicular testosterone production were still reduced, whereas 24 h after E2 administration both testosterone and LH levels had returned to control levels. One and 3 h after injection of 500 ng estradiol, plasma and tissue testosterone levels, as well as testicular testosterone production, were decreased. However, this low dose of E2 also caused a decrease in LH plasma levels. In order to investigate whether estrogens would inhibit testicular testosterone synthesis or release by mechanisms other than inhibition of LH secretion, estrogen or vehicle only were injected into hypophysectomized animals given exogenous LH. No effects of estrogens on testosterone levels or production were observed in such animals. These findings suppport the view that the observed effect of administered estrogens on testosterone production in rat testicular tissue reflect primarily extra-testicular estrogen actions such as the negative feedback effect on LH secretion.