Effect of a nonsteroidal antiandrogen, flutamide on intraluminal acidification in rat testis and epididymis

Summary. Flutamide, a pure antiandrogen was administered to intact adult male rats to study the effect of altered availability of hormones on in situ pH, PCO₂ and bicarbonate concentration ([HCO⁻₃]) of seminiferous tubules, proximal caput, middle caput, middle corpus, and proximal cauda epididymidis. The weights of the epididymis and ventral prostate as well as the plasma testosterone level showed antiandrogenic effects of flutamide. Relative to controls, flutamide elevated significantly in situ pH in proximal caput, middle caput, middle corpus and proximal cauda epididymidis but not in seminiferous tubules. In situ PCO₂ values in the above segments, after flutamide, were indistinguishable from controls and from each other but all values remained significantly higher than systemic arterial blood PCO₂. Flutamide treatment did not change the [HCO⁻₃] in systemic arterial blood or seminiferous tubules but increased markedly the values in proximal caput and middle caput. The results of the present studies support the view that luminal acidification in the rat epididymis is under androgen control and may be important for sperm maturation and storage.     

Effect of 5-alpha-reductase inhibitor, 4-MAPC, on testicular descent in male rat

Testicular descent has been reported to be a dihydrotestosterone (DHT) dependent event. To further elucidate the role of DHT in the process of testicular descent, a group of rats were treated with the 5-alpha reductase inhibitor, 4-MAPC, from birth to day 28 of age and the incidence of testicular descent as well as ventral prostate weight was noted at day 29 of age. It was determined that in the doses used, 4-MAPC failed to prevent testicular descent. Because 4-MAPC inhibited ventral prostate weight by only 53% (as compared to a 75% inhibition by castration), the failure of the 4-MAPC to prevent testicular descent could be due to its inability to completely inhibit tissue 5-alpha reductase activity. The results of this study do not mitigate against the role of other nonhormonal factors working in tandem with DHT in the induction of testicular descent in this animal model.     

Time-specific effects of mono-n-butyl phthalate on the transabdominal descent of the testis in rat fetuses

OBJECTIVE: To determine the time-specific effects of mono-n-butyl phthalate (MBP) on the transabdominal migration of the testis in fetal rats. Materials and methods Three groups of pregnant rats were administered MBP by stomach-tube feeding when the fetus was at 7-10 days of gestation in group 1, 11-14 days in group 2, and 15-18 days in group 3; controls (group 4) were given vehicle only from 7-18 days. At 20 days of gestation the fetuses were obtained by Caesarean section, and the position of the testes, the development of the gubernaculum, cranial suspensory ligament and the epididymis were examined. RESULTS: The timed intervals of MBP administration showed that the maximum inhibition of transabdominal testicular descent was at 15-18 days of gestation. There was an elongated gubernaculum and hypertrophic cranial suspensory ligament in the MBP-treated rat fetuses. Furthermore, the epididymis showed a few small ducti deferentia, although there were no remarkable changes in either the Sertoli and Leydig cells in these testes. The mean (SEM) content of testicular testosterone was significantly less (P < 0.001) in the MBP-treated rats, at 50.9 (3.8) pg/testis, than in the controls, at 676 (33.3) pg/testis. CONCLUSIONS: These findings indicate that a brief exposure to MBP during fetal development can inhibit the transabdominal migration of the testis and reduce testosterone content in rats, although the relationship between migration and the testicular testosterone content remains unknown.     

The antiandrogen flutamide perturbs inguinoscrotal testicular descent in the rat and suggests a link with mammary development

Aim

Inadequate androgen activity is a likely cause of cryptorchidism in humans, affecting inguinoscrotal testicular descent. Flutamide, a nonsteroidal antiandrogen, produces cryptorchidism in rats. We aimed to determine the anatomical and histologic effects of flutamide.

Methods

Time-mated Sprague-Dawley female rats were injected subcutaneously with flutamide (75 mg/kg in sunflower oil) on days 16 to 19 of pregnancy. Embryonic (E) and postnatal (P) male offspring were collected (E16, E19, P0, P2, P4, P8) in control and flutamide-treated groups (n = 5-10). Samples were fixed in 4% paraformaldehyde. Five-micrometer-thick sections were prepared for hematoxylin and eosin, trichrome and immunohistochemical stains (Desmin, TuJ1, Ki67). This identified muscle and neural cells and areas of cell proliferation.

Results

Postnatally, the gubernaculum in flutamide-treated rats had more mesenchyme and muscle than controls. Gubernacular eversion failed, and mammary tissue persisted around the gubernaculum in flutamide-treated rats. Flutamide had no effect on embryonic gubernacular anatomy and histology.

Conclusions

Prenatal androgens altered postnatal gubernacular anatomy and histology in the postnatal period. Our findings indicate that the failure of gubernacular differentiation and migration may be because of the ongoing presence of mammary tissue in the region of the external inguinal ring.     

Effect of division of genitofemoral nerve on testicular descent in the rat

The gubernaculum, which has an important role to play in testicular descent, is richly supplied by the genital branch of the genitofemoral nerve through its scrotal attachment. In neonatal rats the genitofemoral nerve overlying the psoas muscle was divided before inguinal descent would normally occur, and the effect of this procedure on subsequent testicular descent was observed. Denervation of the gubernaculum caused the testes to remain in the abdomen. The significance of this finding in the rat is that an intact genitofemoral nerve is an essential prerequisite for normal descent, perhaps by allowing the gubernaculum to evert.     

Dissociation of testis and epididymis in incomplete descent

Failure of fusion between testis and epididymis will usually be encountered during operations for undescended testis in children and for infertility in adults. In 325 groin dissections for undescended testis monorchism was diagnosed in 3.7% and nonfusion of testis and epididymis in 1.2%. Case reports of three unilateral and one bilateral conditions are presented. Intraoperative misjudgement of this condition is likely to occur if the blind ending epididymis is mistaken for an atrophic testis. Careful search for the missing testis is mandatory.     

Ultrastructural interrelationship between the pineal gland and the testis in the male rat

The ultrastructural interrelationship between the pineal gland and testis was evaluated in the rat. Wistar rats were divided into 6 groups. Groups I and II were sham-orchidectomized and orchidectomized rats, respectively. Rats in group III were orchidectomized and daily injected with testosterone propionate (TP) for 1 month. Groups IV and V were sham-pinealectomized and pinealectomized, respectively. Group VI was pinealectomized and daily injected with melatonin for 2 months. All animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II, and III and the testes of groups IV, V, and VI were removed and weighed. All specimens were examined by electron microscopy. Orchidectomy caused an increase of lipid droplets, cytoplasmic dense bodies, and lysosomes. Rough endoplasmic reticulum, Golgi apparatus, and mitochondria were extensive in the cytoplasm. TP administration to orchidectomized rats resulted in formation of less extensive lipid droplets and mitochondria. In pinealectomized rats, golgi complex, mitochondria, and enlarged smooth endoplasmic reticulum were extensive in the cytoplasm of Leydig cells. Formation of cytoplasmic secretory granules and osmiophilic bodies was observed. Testicular weight increased compared to group IV. Melatonin decreased testicular weight in comparison to group V and prevented ultrastructural changes. Pinealectomy and orchidectomy caused hyperactivity in Leydig cells and pinealocytes, respectively, which suggests a mutual relationship between the pineal gland and testis in the rat.     

Effect of mercuric chloride on membrane—bound enzymes in rat testis

Aim: To study the effect of mercuric chloride on the membrane-bound enzymes. Methods: The effect of mercuric chloride at two different doses, 1 mg/kg (low dose) and 2 mg/kg (high dose), orally for 30 days, was observed on the membrane-bound enzymes in the testis of adult albino rats. Results: Mercuric chloride significantly decreased the body weight and testis weight in the high dose group (P<0.05), but not in the low dose group. The activities of 5' nucleotidase and adenosine triphosphatases were markedly decreased (P<0.01) in the testis of both groups. Alkaline phosphatase and γ-glutamyl transferase activities were significantly increased (P<0.01) in both groups. However, the effect was more pronounced in the high than in the low dose groups. Conclusion: The dose dependent effect of mercuric chloride on these enzymes may affect the membrane characteristics and thereby the fertility of the animal. (Asian J Androl 2002 Dec; 4:309-311)     

On the psychopathology of patients with disorders in the descent of the testis

The authors deal with disorders in the descent of the testis and analyse the causes and manifestations from the point of view of fertility and indications to medical treatment or early surgery. Thirty-nine patients were examined and diagnosed as unilateral or bilateral cryptorchism and retention of the testis. The spermatogenetic functions in individual diagnosis and type of operation are described. They wish to ascertain a mutual connection between sexual function and neurotic symptoms in operated patients with regard to the 3 diagnostic groups.     

Effect of sleep deprivation on the physiological status of rat testis

The effect of alteration of central turnover of monoamines on the intratesticular mechanisms in the testis of rats was studied after REM sleep-deprivation. The reduction in the weights of ventral prostate, seminal vesicles and decreased activity of beta-glucuronidase in kidney reflected decreased availability of testosterone to the target organs. Decreased activities of lysosomal enzymes, acid phosphatase and beta-glucuronidase were associated with a decreased steroidogenic activity in the testis. The active mediation of lysosomal enzymes in the testicular function under altered condition was indicated.     

Effect of testosterone deprivation on expression of the androgen receptor in rat prostate, epididymis and testis

Adult rats were treated with ethane dimethane sulphonate (EDS) to eliminate the Leydig cells. This treatment resulted in very low levels of testosterone in the blood and in the testis. Furthermore, histological evaluation of spermatogenesis showed no marked differences between control and EDS-treated animals. In the ventral prostate, 5 days after EDS-treatment, a 4.0 +/- 0.3-fold up-regulation of androgen receptor (AR) mRNA was observed, together with a 2.2 +/- 0.2-fold increase in actin mRNA. In the epididymis, a 2.0 +/- 0.5-fold increase in AR mRNA level was observed, without a change in actin mRNA level. In the testes of EDS-treated rats, the AR mRNA level was not changed (1.02 +/- 0.17-fold of controls), and there was also no change in actin mRNA level at 5 days after EDS-treatment. These results indicate that AR mRNA expression in the ventral prostate and epididymis is regulated differentially by testosterone when compared to regulation in the testis. Testicular androgen binding sites were assayed by Scatchard analysis of the binding of 3H-R1881 to a nuclear fraction, that was isolated by a method which involved the use of liquid nitrogen and high sucrose buffer. The number of specific binding sites per testis in EDS-treated rats with testosterone-implants, remained unaltered compared to control rats (9.1 +/- 1.4 pmol/testis). In these rats, 20% of the normal testicular testosterone level was sufficient to maintain the androgen receptor in a tight nuclear binding (transformed) form. In testes from EDS-treated rats without testosterone-implants, the AR did not fractionate into the nuclear fraction; however, the total testicular AR content in these animals was close to control levels, as measured by nuclear 3H-R1881 binding after receptor transformation through injection of a high dose of testosterone (10 mg) 2 h before killing the rats (testosterone pulse). In the different experimental groups, FSH was not required to maintain the total testicular AR content (ligand binding). Immunoprecipitation and Western blotting of the testicular AR using specific monoclonal and polyclonal antibodies indicated that the total testicular amount of immunodetectable AR protein in long-term testosterone deprived rats was very low when compared to that in control rats or rats with testosterone-implants. This is in disagreement with results obtained in the ligand binding assay, and may point to a structural modification of the AR in the testis that possibly occurs in the prolonged absence of androgens.     

雌二醇对大鼠睾丸组织生长发育的影响

目的　研究雌二醇对睾丸组织生长发育的影响及作用机理。方法　以雄性幼年SD大鼠为对象,设实验组和对照组,实验组大鼠皮下注射苯甲酸雌二醇(E2B,0.04mg/g体重),于注药后第14、28、42、56天取材。行睾丸重量测定、组织病理学观察和凝集素(ConA，GS-I，PNA，SBA和DBA)组织化学实验。结果　实验组睾丸重量(1×10     

Histological findings of the testis in male infertility

For successful treatment of male infertility, the pregnancy-expectant group must have a testis size larger than 12 ml and the FSH/LH index less than 0.99.     

雄激素对结石诱导雄鼠肾内结晶体的影响

目的探讨雌激素对尿石症患者的影响。方法用0．5％乙二醇诱导结石形成，建立4组动物实验雄鼠模型。A组：去势结石组；B组：去势 皮下注射睾丸酮（3mg／d）结石组;C组：结石对照组；D组；正常对照组（标准无结石饮食）。4组雄鼠饲养4周后同时宰杀，分别测定和比较他们血清Testo、FSH、LH、E2、PRL、Prog，肾内晶体沉和部位及程度。结果A、B、C各组间差异均有显著性（P＜O．001）。结论雄性激素对尿石症有一定影响。     

Effect of gestational diabetes mellitus on testis and pancreatic tissues of male offspring

The purpose of this study was to determine the effect of gestational diabetes mellitus (GDM) on some reproductive characteristics, testicular and pancreatic oxidative status and pancreatic endocrine receptor densities of male offspring at post‐pubertal stage. A total of 36 1‐day‐old Wistar Albino male offspring including 12 pups of nontreated mothers (control group), 14 pups of 40 mg/kg STZ‐injected mothers (STZ‐40 group) and 10 pups of 60 mg/kg STZ‐injected mothers (STZ‐60 group) were used. The offspring were euthanised on post‐natal day 60, their blood, reproductive organs and pancreatic tissues were obtained and examined. When compared with the control group, there was a significant decrease in body and absolute reproductive organ weights, serum testosterone level, testicular and pancreatic catalase activities, pancreatic glutathione level, epididymal sperm concentration of both STZ‐40 and STZ‐60 groups as well as in testicular glutathione level of only STZ‐60 group. Significant increases were determined in testicular and pancreatic malondialdehyde level and glutathione peroxidase activity in both groups and in fasting serum glucose of only STZ‐60 group in comparison with the control group. Although some histopathological damages were observed in testes of both STZ‐40 and STZ‐60 groups, there were no detectable differences between the groups in density of insulin, glucagon and somatostatin receptors in pancreas. In conclusion, GDM has negative effects on reproductive efficiency and testicular–pancreatic tissue oxidant/antioxidant balance of male offspring at post‐pubertal stage.     

Effect of the nonsteroidal antiandrogen nilutamide on adrenal androgen secretion

The nonsteroidal androgen-receptor antagonist nilutamide has previously been shown to inhibit adrenal androgen steroidogenesis in patients with prostatic carcinoma treated in combination with an LHRH agonist. In order to understand better the mechanisms subserving this observation, we have studied the effects of nilutamide alone on the serum concentrations of androstenedione (A), dehydroepiandrosterone (DHEA), and DHEA-sulphate (DHEA-S) in 12 patients with prostatic cancer and compared them with those achieved in 21 patients treated with the agonist D-Trp-6-LHRH. In addition, the adrenocorticotropic hormone (ACTH)-stimulated adrenal response and the thyrotropin releasing hormone (TRH)-stimulated prolactin (PRL) response observed in the patients treated with nilutamide were compared with a control group of healthy age-matched controls. No significant variation in the basal concentrations of adrenal androgens occurred either within or between both treatment groups. In response to ACTH, a decreased 17-α hydroxyprogesterone (17-OHP) accumulation and an augmented A/17-OHP ratio were observed in the antiandrogen group (P < 0.05 for both), suggesting the partial removal of the 17,20 lyase block which was distinctive of the untreated controls, while no significant difference was found for other steroids. Basal PRL levels were not affected by the antiandrogen, but the response to TRH was increased. We conclude that no significant inhibition of adrenal androgen secretion occurs after nilutamide or LHRH agonist treatment. Rather, administration of the antiandrogen alone may partially remove the physiologic decrease in adrenal androgen secretion observed in the elderly. © 1994 Wiley-Liss, Inc.     

Bilateral spontaneous descent of the testis after the age of 10: subsequent effects on fertility

Fertility after late spontaneous descent of the testes in 45 men with previous bilateral undescended testes was evaluated on the basis of seminal analysis and concentrations of follicle-stimulating hormone (FSH) in serum. Only 15 (33 per cent) were found to have a normal fertility as estimated from the results of the total semen analysis, whereas 21 (47 per cent) were classified as being sterile or having severely reduced fertility. Elevated serum FSH concentrations in the majority of men with subnormal sperm densities supported the results of the semen analysis, indicating impaired spermatogenesis. These findings suggest that the expectant attitude in the treatment of cryptorchidism does not seem to be justified in terms of fertility and combined with recent histomorphological studies favour a more active and early treatment of undescended testes.     

全身性非特异性免疫反应对大鼠睾丸几种酶活性的影响

为确定全身性非特异性免疫反应对大鼠睾丸功能的影响而进行此项研究。动物经１０天碳粒注射,睾丸内ＬＤＨ总活性、ＬＤＨｘ活性比,以及琥珀酸脱氢酶、酸性磷酸酶、非特异性酯酶、酸性酯酶等酶的活性,经酶组织化学染色、生物化学检测,以及凝胶电泳分析等显示,它们在活性强度、活性分布以及同工酶谱等方面均发生了明显改变。动物血皮质酮水平明显变化。实验结果提示：一个单纯性的全身性非特异性免疫反应可对睾丸的功能造成明显损     

甲氧滴滴涕对雄性大鼠生精细胞的细胞周期影响

目的探讨甲氧滴滴涕(MXC)对雄性大鼠生精细胞的细胞周期影响。方法实验动物分为对照组,溶剂组,5 d、10 d和15 d MXC实验组。用流式细胞仪检测染毒雄性大鼠生精细胞周期变化。结果随着MXC染毒时间延长与对照组比较,实验组G0/G1期与S期细胞数减少,G2/M期细胞数增多(P<0.05),单倍体细胞减少,二倍体与四倍体细胞增多(P<0.05);除5 d实验组二倍体与四倍体细胞荧光强度强外,其余各实验组的单倍体、二倍体和四倍体细胞荧光强度均减弱(P<0.05);溶剂组与对照组间的变化无显著性差异(P>0.05)。结论MXC可引起大鼠睾丸生精细胞S期抑制及G2期阻滞。