Quantitative maintenance of spermatogenesis in cyclosporine-treated rats by exogenous administration of testosterone propionate

The authors had previously shown that the subcutaneous administration of cyclosporine (CsA) resulted in an impairment of spermatogenesis. Testosterone levels declined and gonadotropin levels increased, suggesting that CsA primarily affects the synthesis and secretion of testosterone. In this study, the authors attempted to determine whether the exogenous administration of testosterone would maintain spermatogenesis in animals treated with a very high dose of CsA. Sexually mature, male Sprague-Dawley rats were treated subcutaneously with CsA (40 mg/kg per day) alone, or in combination with testosterone propionate (TP; 2 and 5 mg/d per rat), for 14 days. As expected, CsA reduced the body and reproductive organ weights and the levels of serum testosterone, while elevating the levels of follicles-stimulating hormone (FSH) and luteinizing hormone (LH). Quantitative analysis of spermatogenesis revealed a decline in all the different types of germ cells in tubules at stage VII of the cycle of the seminiferous epithelium. Administration of TP in 2 and 5 mg/d per rat doses restored the body and reproductive organ weights and the circulating levels of FSH. The serum levels of LH were below the assay's minimum level of detectability. Analysis of spermatogenesis revealed a dose-dependent increase in the germ cell counts after the administration of 2 and 5 mg of TP. The circulating levels of CsA were also significantly reduced after TP administration. These results revealed that CsA-induced alteration in spermatogenesis can be prevented by the exogenous administration of testosterone.     

Effect of long‐term testosterone propionate or human chorionic gonadotrophin administration on reproductive glands in adult male rabbits

The study was aimed to investigate the effect of testosterone propionate (TP) or human chorionic gonadotrophin (hCG) treatment on reproductive glands in sexually mature male rabbits. A total 36 adult male rabbits were randomly distributed to six equal groups. The first control group (CON), the second treated with low‐dose TP (TPL), the third treated with high‐dose TP (TPH), the fourth treated with low‐dose hCG (CGL), the fifth treated with medium‐dose hCG (CGM) and sixth treated with high‐dose hCG (CGH). At the 16th post‐treatment week, the animals were sacrificed, and the testes and accessory sex glands dissected, weighted and stored at ?20 °C until assay. Testosterone propionate treatment in both doses resulted in reduction (P < 0.01) in testicular weight and increase (P < 0.01) in weight of vesicular gland, paraprostate and proprostate glands. High‐dose TP increased the weight of prostate and bulbouretheral gland (BUG). Testosterone propionate increased total androgen (P < 0.01) with Testosterone (T) predominating in serum, dihydrotestosterone (DHT) predominating in testes and most accessory sex glands. High dose of hCG increased the weight of proprostate and paraprostate glands. Androgen level in serum, testes and accessory sex glands increased (P < 0.01) after hCG treatment.     

The effect of testosterone propionate on wound healing in normal and castrate rats

The dependence of wound healing on testosterone was studied in normal and castrate rats by determination of wound breaking strength (WBS) in dermal wounds, by implantation of subcutaneous polyvinyl sponges (PVS) and by [³H]proline tracer studies. The level of testosterone achieved with various doses of testosterone propionate (TP) was assessed using the androgenic effect of this hormone on prostate and seminal vesicle weights. Exogenous testosterone propionate (0.25 – 3.0 mg/day) produced no acceleration of wound healing as measured by WBS on 14- and 21-day wounds. In castrate rats a mild inhibition of healing (15% decrease in WBS) was found in 14-day wounds but no difference was found between castrate and control in 21-day wounds. The rate of wound collagen synthesis was assessed by measuring the conversion of [³H]proline to [³H]hydroxyproline, a process essentially limited to procollagen synthesis. It was not altered by castration, or by administration of testosterone propionate (0.0625 – 1.0 mg/day) to castrate rats. Similarly, deposition of tissue in polyvinyl sponges whether measured as added dry weight or total hydroxyproline did not differ significantly between control and castrate rats receiving testosterone propionate (0–1.0 mg/day). As a method of assessing wound healing, WBS measurements produced the most consistent results. In conclusion, no longterm dependence of wound healing on testosterone was identified in the testosterone-depleted (castrate) rat although some early depression was noted, and no acceleration of the normal process resulted from exogenous testosterone administration in the normal or testosterone-depleted rat.     

Dose-response relationship between testosterone and erectile function: evidence for the existence of a critical threshold

Androgens play an important role in erectile function. However, the dose-response relationship between plasma testosterone levels and penile erection remains unclear. Intact (sham operated) or bilaterally orchiectomized, mature male Sprague-Dawley rats were used. Two weeks after surgery, rats were infused continuously with either vehicle (polyethyleneglycol) or varying doses of testosterone (44, 88, 220, or 440 mug/day) for 14 days using subcutaneous osmotic infusion pumps (study 1). In a separate study, 4 weeks after surgery, rats were infused with a lower range of testosterone doses (11, 22, or 44 mug/day) for 14 days (study 2). In the first study, intact rats had a mean plasma testosterone concentration of 0.56 +/- 0.12 ng/mL ( approximately 1.9 nM), as determined by standard radioimmunoassay. In the second study, a more sensitive enzyme-linked immunoassay was used to measure the lower testosterone levels. Using this assay, intact rats had a mean plasma testosterone concentration of 2.02 +/- 0.59 ng/mL. Intracavernosal pressure measurements indicated that orchiectomy resulted in a significant reduction in erectile function, when compared to intact animals, whereas testosterone infusion restored erectile function to varying degrees. Erectile function was maintained by a wide range of systemic testosterone levels as low as 10%-12% of normal physiological plasma concentrations. Below these concentrations, erectile function was significantly and positively correlated with testosterone plasma levels in a dose-dependent manner. Interestingly, prostate tissue mass was positively correlated to plasma testosterone levels across all concentrations examined. Protein expression of neural nitric oxide synthase (nNOS) and phosphodiesterase type 5 (PDE 5) was reduced in penile tissue from orchiectomized animals and increased in testosterone-infused animals, as assessed by Western blot analyses. We suggest that testosterone at levels approaching one-tenth normal physiological plasma concentration may represent a threshold value, below which erectile function declines in a dose-dependent fashion. However, different androgen-dependent tissues may exhibit varying sensitivities to circulating testosterone with regard to growth and function.     

Flutamide as a tool to study the hormonal regulation of the reproductive tract in the golden hamster

Summary: The effect of flutamide (FLU) administered during 6 weeks at doses of 50 or 100 mg kg⁻¹ body weight, on various reproductive characteristics of sexually active male golden hamsters was studied. The weight of seminal vesicles and epididymides showed a dose dependent inhibition with FLU, while testicular weight exhibited a biphasic response, its value being increased by 20% at lower FLU doses and reduced by 15% at higher FLU doses. An elevation of testicular and epididymal androgen-binding protein (ABP) content and also of testicular testosterone content was observed with both doses of FLU. Serum levels of LH and testosterone exhibited a four-fold increase, at both doses of FLU, while FSH serum level was elevated depending on the dose of FLU used. Results suggest that in the golden hamster the maintenance of the weight of testes and accessory organs depends mainly on androgenic stimulation, while production and transport of ABP is probably regulated by gonadotropins.     

Increased plasma and pituitary prolactin concentrations in adult male rats with selective elevation of FSH levels may be explained by reduced testosterone and increased estradiol production

The roles of testosterone and estradiol in regulating prolactin concentrations were studied in acutely castrated adult male rats receiving subcutaneous Silastic implants of the sex steroids. Testosterone was administered in increasing doses, from subphysiologic to intact levels, both alone and in combination with a small, single dose of estradiol. The study was designed to assess whether a change in the relative rates of sex steroid production could account for an increase in PRL release in the absence of other testicular factors. At very low levels of plasma testosterone, FSH and LH levels were indistinguishable from castrate controls. As plasma testosterone concentration increased, both plasma FSH and LH levels were suppressed progressively to intact levels. When a subphysiologic dose of testosterone was coadministered with a small dose of estradiol, the combined effects produced a midcastrate level of FSH but maintained a normal level of LH similar to the selective increase in FSH concentration observed in men with germinal aplasia. Although PRL levels were indistinguishable in intact and castrate controls, testosterone replacement by capsule increased prolactin in a dose-related manner so that, at the physiologic level of testosterone, prolactin was elevated two-fold (P less than 0.01), similar to the level achieved with estradiol replacement alone. Pituitary prolactin levels also increased with increasing doses of testosterone but values remained within the range measured in intact controls. When estradiol was coadministered with testosterone, the combination produced different effects depending on the testosterone dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of tamoxifen and testosterone propionate in male rats: differential prevention of orchidectomy effects on sex organs, bone mass, growth, and the growth hormone-IGF-I axis

Testis dysfunction can weaken bone and reduce muscle mass as well as impair sexual function. Testosterone (T) therapy has useful effects on sex organs, bone, and muscle in T-deficient males, but prostate concerns can preclude T use in some men. Although estrogens or other drugs can protect bone in men, gynecomastia makes estrogens unappealing, and other drugs may also be undesirable in some cases. Selective estrogen receptor modulators (SERMs) inhibit estrogen-evoked sex organ growth but mimic estrogen effects on bone and cholesterol and are advantageous for some women. SERMs may also be useful in men who must avoid androgens. As a preclinical test of this idea, tamoxifen (a SERM) and testosterone propionate (TP, a classic androgen) were compared for their efficacy in preventing varied effects of orchidectomy (ORX) in adult male rats. ORX led to ventral prostate and seminal vesicle atrophy and decreases in somatic growth, proximal tibia bone mineral density (BMD), and serum growth hormone (GH) and insulin-like growth factor I (IGF-I). ORX also increased anterior pituitary glandular kallikrein, serum cholesterol, and body temperature. Pituitary prolactin (PRL) content was unaltered. ORX effects on sex organs, somatic growth, IGF-I, cholesterol, body temperature, and pituitary kallikrein were prevented by TP at 1 mg/kg (3 doses per week), but BMD and GH were unresponsive. ORX effects on BMD and GH were prevented by TP at 10 mg/kg, but this dose evoked supraphysiologic increases in sex organs and PRL, failed to restore somatic growth, and further reduced IGF-I. Tamoxifen (1 mg/kg daily) prevented ORX effects on BMD, GH, and cholesterol without altering basal or TP-induced sex organ growth and further reduced IGF-I and somatic growth. Tamoxifen did not alter basal PRL but blocked increases caused by TP at 10 mg/kg. In summary, tamoxifen prevented ORX effects on bone and cholesterol in male rats without affecting sex organs or PRL and might be useful for men who must avoid androgens. Unexpectedly, a TP dose that replicated testis effects on sex organs and other targets had no effect on BMD or GH, and a larger TP dose that restored BMD and GH was worse at replicating normal male physiology. In addition, correlation/regression results suggested that the GH-IGF-I axis contributes to changes in BMD.     

LY207320 (6-methylene-4-pregnene-3,20-dione) inhibits testosterone biosynthesis,androgen uptake, 5α-reductase,and produces prostatic regression in male rats

LY207320 is an in vitro inhibitor (estimated IC₅₀ = 0.06 μM) of steroid 5α-reductase that catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT). In contrast, LY207320 was only moderately active against rat prostatic 5α-reductase in vivo (32% inhibition at 50.0 mg/kg single dose). LY207320 did, however, inhibit the in vivo uptake of [³H]-T by the prostate. The antiprostatic and endocrine effects of this agent were evaluated following daily (21 days) administration to castrated, androgen-supplemented castrate, and intact rats. LY207320, which has modest progestational competitive binding activity, does not bind to rat prostatic androgen or uterine estrogen cytosolic receptors. In the castrated male rat, subcutaneously (s.c.) administered LY207320 had no androgen agonist activity, as evidenced by a lack of accessory sex organ weight gains. Administration of s.c. LY207320 to intact rats for 21 days at doses greater than 5.0 mg/kg-day produced significant (P <0.05) reductions of seminal vesicle and ventral prostatic weights (maximal regression = ?65% and ?40% from control values, respectively at 50.0 mg/kg-day). The compound had no regressive activity on male accessory sex organs when administered orally. LY207320 did not alter circulating prolactin, LH, or corticosterone levels, but at high doses (>m50.0 mg/kg-day), lowered circulating T[?67% from intact control levels (P <0.05)]. Histological analysis of the rat ventral prostates (RVPs) in LY207320-treated rats was consistent with an androgen-deprived state. Decreased circulating androgens and prostatic regression are associated with inhibition of testicular 17α-hydroxy/C17,20-lyase enzyme activity (IC⁵⁰ = 0.06 μM). These findings support the contention that LY207320 is a physiological antagonist of androgen action in male rats, and that its effects are mediated primarily through inhibition of testicular androgen production rather than accessory sex organ 5α-reductase. © 1993 Wilcy-Liss, Inc.     

Comparison of the antispermatogenic effects of a new D-homo-steroid and testosterone in rabbits

In comparison to testosterone, 18β-hydroxy-18α-methyl-16α, 17α-methylene-D-homo-5α-androstane-3-one (D-homo-S) shows more pronounced anti-gonadotrophic than androgenic properties in rats. The present study was initiated in rabbits to investigate the potential of D-homo-S to suppress spermatogenesis. D-homo-S in sesame oil was administered at the doses of 0.1 (DI), 3 (D II) or 10 mg (D III) per rabbit each day for 8 weeks. During treatment serum testosterone, sperm concentration and quality of sperm motility decreased, whereas sex drive, semen volume and seminal plasma concentrations of fructose and zinc were not changed in any of the groups. Testicular weight and intratesticular testosterone concentration decreased significantly in groups D II and DIII, while weights of accessory sex glands increased in those groups. Testosterone in the same dose regimen did not suppress sperm count, motility or serum testosterone, however, seminal plasma zinc concentration in group TIII and fructose in group TI increased. Testicular weight and intratesticular testosterone concentration decreased in group TIII only. On the other hand, the weight of the accessory sex glands increased in the same group.
In conclusion, D-homo-S suppresses spermatogenesis and increases accessory sex gland weights at doses, when testosterone is still ineffective. Thus, in rabbits D-homo-S appears to be a more potent androgen than testosterone but a dissociation between antigonadotrophic and androgenic properties could not be observed.     

Atrazine effects on testosterone levels and androgen-dependent reproductive organs in peripubertal male rats

Previous studies have reported that atrazine, a widely used herbicide that selectively inhibits photosynthesis in broadleaf and grassy weeds, has adverse effects on reproductive function in the male, suggesting a direct effect of atrazine on the hypothalamicpituitary-testicular axis. As yet, however, no studies have critically examined the doses of atrazine that elicit such effects, and few have focused on the mechanism by which atrazine acts. Herein we report a dose-response study of the effects of atrazine ingestion on reproductive function in male Sprague-Dawley rats during a critical developmental period, the peripubertal period. Atrazine was administered by gavage to rats from day 22 to day 47 of age, at doses of 1-200 mg/kg body weight per day. Atrazine administration of up to 50 mg/kg per day had no effect on any of the measured variables. Serum testosterone concentration was reduced by atrazine at doses of 100 and 200 mg/kg per day, as were seminal vesicle and ventral prostate weights. Intratesticular testosterone concentration was reduced in parallel with serum testosterone, suggesting that the reductions in serum testosterone resulted from reduced testosterone production by Leydig cells or from changes in testosterone metabolism within the testis, or both. Serum luteinizing hormone (LH) concentration was reduced despite the reduced serum testosterone, suggesting an effect on the hypothalamus, the pituitary gland, or both. At the termination of the study, the average body weight of rats receiving atrazine at 100 mg/kg per day was found to be reduced by approximately 9%. This suggested the possibility that the effects of atrazine on the reproductive tract may not be direct, but rather, the noted deficits of the male reproductive tract resulted from reduced food intake by the treated rats. We tested this by feeding control (vehicle-gavaged) rats amounts of food equivalent to that consumed by the atrazine-fed rats, and then assessing reproductive tract endpoints. Even mild food restriction resulted in reductions in serum testosterone concentration, in the weights of androgen-dependent organs, and in serum LH concentration; the same deficits that were seen in atrazine-gavaged rats. Indeed, the effects of atrazine on the male reproductive tract seen in rats receiving atrazine at greater than 50 mg/kg per day could not be distinguished from the effects of reduced food consumption. These results suggest that caution must be exercised before concluding that atrazine (or any potentially toxic chemical) has direct, detrimental effects.     

Some effects of furazolidone on the testis and plasma levels of testosterone, luteinizing hormone and prolactin in mature male turkeys

Adult male turkeys were treated orally with furazolidone at doses of 1, 2.5, S or 20 mg/kg for 14 days and their plasma analysed for luteinizing hormone (LH), testosterone and prolactin (PRL) concentrations before, during and after treatment. At 20 mg/kg the drug produced a significant decrease in the plasma levels of LH and testosterone at the end of treatment, whereas at 5 mg/kg the drug had no significant effect. Prolactin concentrations were unaffected by any of the drug doses used. Intramuscular injection of luteinizing hormone releasing hormone (LHRH) at a dose of 5 μg/kg produced after 30 min a significant rise in plasma levels of LH, an effect that was decreased significantly by treatment with 20 mglkg furazolidone. Incubation of normal turkey semen with graded doses of furazolidone or nitrofura-zone for up to 30 min resulted in a dose- and time-dependent decrease in sperm motility. At a concentration of 20 mg/ml a complete absence of sperm motility was observed after incubation with either drug, although, on the whole, nitrofurazone seemed more potent than furazolidone as a sperm-immobilizing agent. Histological changes occured in the 20 mg/kg group and consisted of a decrease in spermatocyte production, corrugation of sperm cell nuclear envelopes and distention of the endoplasmic reticulum of elongate spermatids. It is concluded that furazolidone depresses pituitary LH output but may, in addition, directly affect spermatogenesis and sperm motility.     

The testosterone mimetic properties of icariin

Aim:To evaluate the testosterone mimetic properties of icariin.Methods:Forty-eight healthy male Sprague-Dawleyrats at the age of 15 months were randomly divided into four groups with 12 rats each:the control group(C),the modelgroup(M),the icariin group(ICA)and the testosterone group(T).The reproductive system was damaged by cyclo-phosphamide(intraperitoneal injection,20 mg/kg-day)for 5 consecutive days for groups M,ICA and T,at the sixth day,ICA(gastric gavage,200 mg/kg·day)for the ICA group and sterandryl(subcutaneous injection,5 mg/rat.day)for the Tgroup for 7 consecutive days,respectively.The levels of serum testosterone,luteinizing hormone(LH),folliclestimulating hormone(FSH),serum bone Gla-protein(BGP)and tartrate-resistant acid phosphatase activity in serum(StrACP)were determined.The histological changes of the testis and the penis were observed by microscope withhematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling(TUNEL),respectively.Results:(1)Icariin improved the condition of reproductive organs and increased the circulating levelsof testosterone.(2)Icariin treatment also improved the steady-state serum BGP and might have promoted boneformation.At the same time,it decreased the serum levels of StrACP and might have reduced the bone resorption.(3)Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells.Conclusion:Icariin has test-osterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.(Asian J Androl2006 Sep;8:601-605)     

Cyclosporine: its effects on testicular function and fertility in the prepubertal rat

The authors examined the effects of the immunosuppressive drug cyclosporine (CsA) on the male reproductive system in prepubertal rats. Twenty-one-day-old rats were subcutaneously injected with either cremaphorsaline vehicle or CsA (1 and 2 mg/kg/d). The animals were treated until they were 66 days old. Cyclosporine did not affect the weights of the body or testis but decreased the weights of all sex accessory organs. Quantitative analysis of the tubules in stage VII of spermatogenesis revealed a decline in the cell counts of pachytene spermatocytes and step VII spermatids. Testicular and epididymal sperm counts and motility were decreased by 50% and fertility by 60%. Cyclosporine lowered serum testosterone despite an elevation of LH, indicating that the drug directly inhibited testosterone synthesis. Serum creatinine levels were normal in the treated animals, precluding renal failure as the cause for this impairment. Intratesticular concentrations of pregnenolone and 17-hydroxy progesterone were significantly elevated, while those of progesterone, androstenedione, and testosterone were markedly reduced. Determination of steroidogenic enzyme activities indicated that the administration of CsA inhibited the activity of delta 5-3B-hydroxy steroid dehydrogenase-delta 5-4 isomerase (3 beta-HSD). These results clearly indicate that CsA in the doses used is harmful to the male reproductive function in prepubertal rats.     

Effect of sodium arsenite on spermatogenesis,plasma gonadotrophins and testosterone in rats

To investigate the effect of arsenic on spermatogenesis. Methods: Mature (4 months old) Wistar rats were intraperitoneally administered sodium arsenite at doses of 4, 5 or 6 mg-kg^-day1 for 26 days. Different varieties of germ cells at stage VII seminiferous epithelium cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone (FSH), lutuneizing hormone (LH), testosterone and assessment of the epididymal sperm count. Results: In the 5 and 6 mg/kg groups, there were significant dose-dependent decreases in the accessory sex organ weights, epididymal sperm count and plasma concentrations of LH, FSH and testosterone with massive degeneration of all the germ cells at stage VII. The changes were insignificant in the 4 mg/kg group. Conclusion: Arsenite has a suppressive influence on spermatogenesis and gonadotrophin and testosterone r     

Changes in testosterone and dihydrotestosterone levels in male rat accessory sex organs, serum, and seminal fluid after castration: establishment of a new highly sensitive simultaneous androgen measurement method

It is known that abnormal androgen dynamics in the tissues is a cause of androgen-dependent disorders. Investigation of tissue androgen levels could provide a clue to the elucidation of disorders. However, it is difficult to measure a trace amount of androgen in the tissues. We established a highly sensitive simultaneous quantification method of testosterone and dihydrotestosterone (DHT), which play the most important roles in the body among androgenic steroids in trace amounts, and investigated time course changes in testosterone and DHT levels in male accessory sex organs, serum, and seminal fluid after castration in rat models. In addition, changes in the testosterone/DHT ratio of male accessory sex organs and seminal fluid were observed. The simultaneous testosterone and DHT measurement method established by us was validated. Intra-assay variation and interassay precision and accuracy were all within +/-20%, and the quantification limits of testosterone and DHT were both 15.6 pg/g. With the use of this method, the testosterone and DHT levels in the prostate, seminal vesicles, and serum immediately after castration were similar to those previously reported. The testosterone and DHT levels were 350 pg/g and 605 pg/g, respectively; which showed dominance of DHT in seminal fluid, although it was not as marked as that in the male accessory sex organs. Androgens decreased with time after castration in the accessory sex organs, serum, and seminal fluid. In the prostate and seminal vesicles, testosterone and DHT decreased to about 50% and about 2% of the normal levels, respectively, 72 hours after castration. The serum levels were under the quantification limits 6 hours after castration and thereafter. In seminal fluid, the testosterone and DHT levels decreased to 49% and 35% of normal levels, respectively, 72 hours after castration. The testosterone/DHT ratio in the male accessory sex organs was lower in the prostate (0.06) than in the seminal vesicles (0.13) immediately after castration. In the seminal fluid, changes in the ratio were small compared with those in the accessory sex organs and serum. These results showed that our method was capable of measuring testosterone and DHT in very small amounts of samples such as prostate biopsy specimens, and it might provide a clue to the elucidation of the pathology of androgen-dependent disorders.     

Effects of combination therapy with a luteinizing hormone-releasing hormone agonist and chlormadinone acetate on rat prostate weight and plasma testosterone levels

We investigated whether the combination of chlormadinone acetate (CMA) and a luteinizing hormone releasing hormone (LH-RH) agonist, leuprorelin acetate (leuprorelin), more markedly decreased ventral prostate and seminal vesicle weights and plasma sex hormone levels in male rats. Four weeks after administration of 0.28, 0.84 or 2.8 mg/kg of leuprorelin, ventral prostate weights significantly decreased (53.8, 54.4 and 64.1%) and the plasma testosterone levels significantly lowered, but not dose-dependently. After repetitive administrations of 3 and 30 mg/kg/day of CMA, the rates of ventral prostatic atrophy were 37.1 and 65.9%, respectively. Although there was no change in the plasma testosterone level at 3 mg/kg, 30 mg/kg of CMA significantly decreased the level. A combination of leuprorelin (0.28 mg/kg) and CMA (3 or 30 mg/kg) more potently induced ventral prostatic and seminal vesicle atrophy than leuprorelin alone. Furthermore, a combination of leuprorelin and CMA (30 mg/kg) more markedly decreased the plasma testosterone level. According to the pharmacokinetic data for CMA in male rats, the doses of CMA correspond to the clinical dose. These findings suggest that combination therapy with an LH-RH agonist and CMA is more useful than therapy with the agonist alone in the treatment of prostate cancer.     

雌二醇和睾酮对雄鼠下丘脑-垂体的反馈调节作用

4组(每组n=5)成年雄性 S-D 大鼠,去势后7天,分别肌注7天的丙酸睾丸酮(T 组)、苯甲酸雌二醇(E_2组)、丙酸睾丸酮+胃灌注三苯氧胺(T+FTMX 组)和豆油(对照组)。然后用放射免疫法测定各组大鼠下丘脑促性腺激素释放激素(GnRH)含量和外周血促黄体生成素(LH)水平。结果示:T 和E_2组大鼠平均血浆 LH 水平分别为1.42±0.23和1.87±0.19U/L,均明显低于对照组的4.46±0.31U/L(P 均<0.01)。下丘脑的 GnRH 含量分别为3196±331和2862±791pg/100mg 湿重组织,均显著高于对照组的1057±34pg/100mg 湿重组织(P 均<0.01)。T+TMX 组大鼠的平均血浆 LH 水平和下丘脑 GnRH 含量和 T 组无差别(P 均>0.05)。     

4-MAPC, a 5 alpha-reductase inhibitor, reduces rat ventral prostate weight, DNA, and prostatein concentrations.

Several compounds, such as 4-MAPC (4-methyl-3-oxo-4-aza-5 alpha-pregnane-20- carboxylate), that inhibit conversion of testosterone (T) to dihydrotestosterone (DHT) by 5 alpha-reductase have been demonstrated to reduce prostate size in rats and dogs. The current studies were undertaken to determine if this effect is due to a reduction in cell number, in epithelial cell synthetic activity, or both. Eight-week-old intact rats were treated daily for 14 days with sesame seed oil, 4-MAPC (10 mg/kg), 4-MAPC + testosterone propionate (TP, 1 mg/kg), or 4-MAPC + TP (3 mg/kg). Rats were killed 24 hours after the last injection. In the animals treated only with 4-MAPC, ventral prostate weight was reduced 37%, but the 14% reduction in total DNA was not significant. The mean intraprostatic concentration of prostatein, a major secretory protein, was reduced 45% (P less than 0.05). The 3 mg/kg dose of TP increased ventral prostate weight, prostatein concentrations, and acid phosphatase activity, even though DNA/ventral prostate was similar to that in control animals. These observations indicate that the reduction in ventral prostate weight in adult rats is due in part to a reduction in cell number, but the primary effect was due to a reduction in synthetic activity, and possibly atrophy of the epithelial cells. Furthermore, TP in pharmacologic doses increased ventral prostate weight and synthetic activity without increasing DNA.     

Effects of cimetidine,progesterone, cannitracin and tolazoline on the weight and DNA content of the testosterone-induced hyperplastic prostate of the rat

Summary The antiandrogenic potency of cimetidine, progesterone, cannitracin and tolazoline was studied in intact immature rats by determination of the weight and DNA content of the ventral prostate. Cimetidine is a H-2-recepter histamine antagonist, cannitracin is an antifungal antibiotic derived from Strp.griseus and tolazoline is an -adrenergic blocker similar to phentolamine. All rats (except the control group) received testosterone propionate (TP) 0.3 mg s.c. with the drugs above every day for one week. Cimetidine, progesterone and cannitracin, but not tolazoline, significantly decreased the weight and DNA content of the hyperplastic prostate induced by TP. The results indicate that cimetidine, progesterone and cannitracin have an antiandrogenic effect. This study provides the basis for investigating the effects of antiandrogen in men with symptomatic benign prostatic hyperplasia.     

Zinc content in the epididymis, vas deferens, prostate, and seminal vesicles of juvenile rhesus monkey (Macaca mulatta): effect of androgen and estrogen

The zinc content in the three segments of the epididymis (caput, corpus, and cauda), vas deferens, seminal vesicles, and prostate of juvenile monkeys was determined by atomic absorption spectrophotometry. Zinc content (micrograms/gm wet weight) was found to be maximum (328) in the vas deferens; in the other organs it measured in the following order: caput 191, corpus 238, cauda 193, prostate 133 and seminal vesicles 85. In order to investigate the endocrine control of the zinc in these organs, two groups of animals were treated with testosterone propionate (2 mg) or estradiol dipropionate (10 micrograms) once daily for 30 days. In response to androgen, a rise in both concentration and content of zinc was evident only in the prostate. The results further suggested that the prostatic zinc may be under dual hormonal control, but in the epididymis and vas deferens it may be under the influence of estrogen. It is concluded that the hormonal effects on zinc content and growth stimulation in accessory sex organs are quite separate and may be under different hormonal control.