Maternal CBZ exposure impairs testicular development,spermatogenesis and sperm parameters in male offspring at puberty

Carbamazepine (CBZ), an anticonvulsant drug, is used by pregnant women and crosses the placental barrier, reaching the embryo/foetus. CBZ inhibits testicular steroidogenesis and may lead to alterations in testicular development, spermatogenesis and male fertility. The purpose of this study was to evaluate the CBZ effects on testicular parameters in the neonatal and pubertal phases, as well as the spermatic parameters of pubertal rats, originated from dams treated during different periods of the pregnancy. Pregnant rats were treated with CBZ (20 mg/kg/day; intraperitoneal route), from 12–20 gestation day (GD) (CBZ12 group) and 15–20 GD (CBZ15 group). The testicular morphometric and stereological analysis of rats aged 4 and 63 days was performed. The oestradiol and testosterone plasmatic levels, as well as spermatic parameters, were achieved at 63 days. CBZ12 group showed a reduction in testicular weight and volume at 4 days post-partum (dpp); however, there was an increase in the seminiferous cords’ length of the CBZ12 and CBZ15 groups. At 63 days, the CBZ12 group showed increases of the daily sperm production and damage in the seminiferous epithelium. The results suggest that CBZ interferes with the testis development and the establishment of the spermatogenic process, which can be detected in the puberty phase.     

Leptin secretion from the epididymal fat pad is increased by the sexual maturation of the male rat

Although leptin has been implicated as an important factor in triggering the onset of puberty in females, much less is known about the role of this adipose tissue hormone in the sexual maturation of males. Previous work in the rat has suggested that the peripubertal rise in testosterone precedes an increase in leptin secretion, and it has been suggested that the testosterone rise induces the leptin increase. These studies examined some of the interactions between leptin secretion and the peripubertal testosterone rise in male rats. Serum leptin concentrations were significantly elevated in young adult male rats compared with immature rats. Cultured epididymal fat pads obtained from adult animals secreted significantly more leptin than did those obtained from immature rats. Castration of immature rats with or without testosterone replacement for 1 week did not result in a significant change in either the serum leptin concentrations or the ability of the epididymal fat pad to secrete leptin. Exposure of epididymal fat to 5 ng/mL of testosterone in vitro resulted in a significantly enhanced secretion of leptin into the media compared with plain media controls. These results confirmed that there is an increase in serum leptin concentrations with sexual maturation in the male rat. They also suggest that this increase is due to an enhanced ability of adipose tissue to secrete leptin. Within a normal physiologic range, testosterone may play a role in inducing this increased ability to secrete leptin.     

6‐Gingerol‐rich fraction from Zingiber officinale ameliorates carbendazim‐induced endocrine disruption and toxicity in testes and epididymis of rats

This study evaluated the protective effects of 6‐gingerol‐rich fraction (6‐GRF) from Zingiber officinale on carbendazim (CBZ)‐induced reproductive toxicity in rats. Adult male rats were treated with either CBZ (50 mg/kg) alone or in combination with 6‐GRF (50, 100 and 200 mg/kg) for 14 consecutive days. Gas chromatography–mass spectrometry (GCMS) analysis revealed that 6‐GRF consists of ten bioactive chemical components with 6‐gingerol being the most abundant (30.76%). Administration of 6‐GRF significantly (p < .05) prevented CBZ‐mediated increase in absolute and relative testes weights as well as restored the sperm quantity and quality in the treated rats to near control. In testes and epididymis, 6‐GRF significantly abolished CBZ‐mediated increase in oxidative damage as well as augmented antioxidant enzymes activities and glutathione level in the treated rats. Moreover, CBZ administration alone significantly decreased plasma levels of testosterone, thyrotropin, triiodothyronine and tetraiodothyronine, whereas follicle‐stimulating hormone was significantly elevated without affecting luteinising hormone and prolactin levels when compared with the control. Conversely, 6‐GRF ameliorated the disruption in the hormonal levels and restored their levels to near normalcy in CBZ‐treated rats. Collectively, 6‐GRF inhibited the adverse effects of CBZ on the antioxidant defence systems, hormonal balance and histology of the testes and epididymis in rats.     

Optimal testosterone concentration for the treatment of prostatic cancer

In order to determine the effects of the absolute concentration of circulating androgens on normal and malignant androgen dependent tissue, normal adult male rats and rats bearing the Dunning R3327H prostatic adenocarcinoma were castrated and implanted with testosterone filled silastic pellets of 1, 3, 5, 10, 20 and 30 mm. designed to release constant amounts of testosterone, or placebo pellets. After 1 month the weights of the ventral prostate and seminal vesicles, serum testosterone and luteinizing hormone levels and the sexual activity of the normal rats were determined. The volume of the prostatic tumor was determined twice weekly for 9 weeks. Serum testosterone increased directly with the length of the implant (r = 0.986). Ventral prostate and seminal vesicle weight increased with increasing serum testosterone (r = 0.984 and r = 0.975 respectively). Changes in prostatic tumor volume did not vary with increasing serum testosterone concentration. In animals with implants of greater than 5 mm. (sig. greater than than castrate value) tumor volume increased markedly and similarly over castrate controls at 9 weeks. Animals with implants of less than or = 5 mm. had tumor volume changes identical to the castrate controls. Sexual activity was relatively normal in animals with implants of greater than 3 mm. A threshold of serum testosterone exists below which the Dunning R3327H tumor is inhibited from growing. This level is higher than the castrate level but is compatible with relatively normal sexual activity. Were there methods to determine the threshold of human tumors, therapy might be individualized to minimize side effects such as the loss of sexual activity.     

The temporal response of rat testes to hCG stimulation during sexual maturation

Serum testosterone responses to a single sc injection of hCG (25 IU/100 g body weight) were monitored for 5 days in rats throughout sexual maturation (22-70 days). Two hours after hCG injection serum testosterone levels rose in 22, 37 and 53 day-old animals and remained elevated for 2 days, returning to control levels on day 3. This response differed markedly from the biphasic secretion of testosterone reported for adult animals. In 70 day-old animals the serum testosterone response approached that seen in adult animals. Testosterone levels were elevated 2 h after hCG injection (25.4 +/- 2.5 ng/ml) and declined significantly at 12 and 24 h to 17.1 +/- 1.0 and 16.1 +/- 3.4 ng/ml, respectively. Testosterone levels tended to increase again on days 2 and 3 (19.9 +/- 2.8 and 21.1 +/- 3.5 ng/ml, respectively) but the increase was not statistically significant. This response differed markedly to the biphasic secretion of testosterone reported for adult animals. In vitro patterns of basal and hCG-stimulated testosterone secretion by decapsulated testes following a single hCG injection also changed during sexual maturation. In 22 day-old animals the testes exhibited refractoriness to in vitro hCG stimulation at 12 h, but testes from 37 day old rats were refractory from 2 to 24 h. In vitro testosterone responses of testes from 53 and 70 day-old rats were similar to that reported for adult rats with a period of refractoriness from 12 h to 2 days. This study demonstrates that during sexual maturation in the rat alterations occur in the temporal patterns of testosterone secretion in vivo and in vitro following hCG stimulation.     

Effect of rutin on diabetic‐induced erectile dysfunction: Possible involvement of testicular biomarkers in male rats

The present study aimed to investigate effects of rutin on diabetic‐induced impairments of sexual behaviour, spermatogenesis and oxidative testicular damage. Diabetes was induced by a single injection of STZ (65 mg/kg) in male adult Wistar rats. Two weeks later, rutin (50 and 100 mg kg^?1 day^?1) was treated to normal and diabetic rats for 5 weeks. Sexual behaviour of the animals was observed by taking stimulus females. At the end of the study, sperm count, motility and viability were recorded. Serum levels of glucose, inflammatory markers and testosterone were also estimated. In penile tissue, cGMP levels were measured, while lipid peroxidation and antioxidant molecules and enzyme activities were determined. Finally, histopathological changes were evaluated in a cross‐section of testis. Diabetic‐induced alterations in male sexual behaviour and sperm count, motility and viability were markedly corrected following 5 weeks of rutin treatment to the diabetic animals. Rutin also attenuated the inhibited serum testosterone and penile cGMP content, while improved diabetic‐associated inflammation and testicular lipid peroxidation and oxidative stress. Histopathological evaluation revealed damaged testicular tissues in diabetic rats, which was protected following rutin treatment. In conclusion, treatment with rutin improved sexual functionality and also protects against diabetic‐induced testicular damage.     

Study on ethane dimethane sulphonate (EDS)-induced spermatogenic damage and protective drugs against this damage in the rat]

The effects of a single administration of ethane dimethane sulphonate (EDS), which has a direct cytotoxic effect on Leydig cells, was assessed for its spermatogenic damage and intratubular androgen level in SD male adult rats. The protective effect of human chorionic gonadotropins (hCG) (s.c.), testosterone propionate (TP) (s.c.) and intratesticular administration of testosterone microcrystal suspension (Tmcs) against the spermatogenic damage in rats EDS given was also evaluated. EDS caused a decrease of the seminiferous tubular diameter and impaired spermatogenesis remarkably; moreover, it also caused significant decreases in intratubular androgen levels. These results suggest that EDS-treated SD male adult rats may be suitable as a model for hormone dependent infertility. The administration of hCG and intratesticular Tmcs prevented tubular damage and increased the intratubular T level. On the other hand, the administration of TP prevented tubular damage while remarkably decreasing intratubular androgen level. In this connection, it was inferred that priming of rats with TP caused an increase in intratubular androgen binding protein, which would stimulate spermatogenesis. The fact that a single injection of Tmcs caused no tubular damage suggests that intratubular T level is one of the factors playing an important role in spermatogenesis and that an intratesticular injection of Tmcs may be useful for the treatment of some cases of idiopathic male infertility.     

Evaluation of the relative importance of endocrine and paracrine factors in control of the levels of inhibin in testicular interstitial fluid

This study aimed to identify the role of endocrine (FSH, LH, testosterone) or paracrine (Leydig or germ cell) factors in control of the secretion of inhibin into testicular interstitial fluid (IF). This was done by measuring inhibin and testosterone levels in IF, and serum gonadotrophin and testosterone levels in adult rats following the destruction of Leydig cells with ethane dimethane sulphonate (EDS), alone or in combination with testosterone ester (TE) supplementation at various doses initiated at various times after EDS treatment. The effect of germ cell loss (induced by local testicular heating) on its own or in combination with the above treatments was also assessed. Treatment with EDS led to major increases in the levels of inhibin in IF and of FSH and LH in serum whilst testosterone levels in IF and serum fell to undetectable levels. Supplementation with TE (1-25 mg) for 21 days from the time of EDS treatment failed to prevent the initial (+3 days) increase in IF levels of inhibin but thereafter suppressed inhibin to control levels or lower and grossly suppressed FSH and LH levels, irrespective of whether the dose of TE administered did (25 or 5 mg) or did not (1 mg) prevent major seminiferous tubule damage. Partial regeneration of Leydig cells and normalization of testosterone levels occurred in rats 21 days after treatment with EDS alone but this failed to normalize inhibin and gonadotrophin levels. When supplementation with TE (25 mg) was initiated at 3, 6 or 9 days after EDS treatment, IF levels of inhibin were normalized within 3 days and maintained thereafter in parallel with suppression of serum FSH and LH to below control levels. Seminiferous tubule damage induced by local testicular heating (43 degrees C for 30 min) led to increased IF levels of inhibin 3 and 14 days later, in parallel with increased serum levels of FSH (but not LH). Suppression of FSH to subnormal levels in heat-exposed rats by TE treatment (25 mg) restored IF inhibin to control levels or below, a change which still occurred when Leydig cells were destroyed by EDS treatment. It is concluded that secretion of inhibin via the base of the Sertoli cell into testicular IF is controlled primarily by FSH, although local factors may play a minor role. These findings have important implications regarding the possible paracrine role(s) of inhibin in IF during puberty and in the normal adult testis.     

Activity of single components of Ferula hermonis on male rat sexual behavior

The influence of the single components of Ferula hermonis extract on sexual behavior was studied in male rats. Sexually potent and sluggish/impotent animals were orally treated acutely (2.5 mg/kg) and subchronically (0.25 mg/kg/day for 10 days) with ferutinin, teferdin and teferin. Ferutinin alone acutely administered in potent rats was able to reduce mount and intromission latencies, while in sluggish/impotent animals, it induced the same effects and additionally shortened the ejaculation latency, as teferdin did. Both substances increased testosterone levels in rats. Unlike teferdin, ferutinin subchronically administered in potent rats negatively affected appetitive and consummatory sexual behavior, reducing also testosterone serum levels. In conclusion, if repetitively administered, ferutinin was able to stimulate sexual behavior after acute ingestion, but exerted a negative influence on the sexual capacity of potent male rats, whereas teferdin only improved copulatory performance of sluggish/impotent animals.     

Long-term outcome of Fowler-Stephens orchiopexy in boys with prune-belly syndrome

Purpose

Intra-abdominal testes in boys with prune-belly syndrome have been conventionally managed by 1 or 2-stage orchiopexy with division of the gonadal vessels. We reviewed a series of adults with prune-belly syndrome to assess the morphological and functional outcome of orchiopexy in childhood with specific reference to the spontaneous onset of puberty, hormonal profiles and sexual function.

Materials and Methods

A total of 41 boys were divided into 3 groups depending on the type of orchiopexy performed, namely group 1—20 with bilateral 1-stage orchiopexy, group 2—10 with unilateral 1-stage and contralateral 2-stage orchiopexy, and group 3—11 with bilateral 2-stage orchiopexy.

Results

In group 1 9 of 20 patients had good scrotal testes bilaterally, 6 had a good scrotal testis on 1 side and 3 had small testes on each side. Two boys required testosterone supplementation but 18 had normal hormonal and sexual function. In group 2 6 of 10 patients had good scrotal testes bilaterally and 4 had a good scrotal testis on 1 side. All patients underwent spontaneous puberty with good sexual function. In group 3 7 of 11 boys had good scrotal testes bilaterally and 3 had 1 good testis with normal puberty and sexual function. These 10 patients underwent spontaneous puberty with good sexual function.

Conclusions

The majority of boys with prune-belly syndrome had a satisfactory outcome after orchiopexy with division of the gonadal vessels with testicular function sufficient to induce puberty and maintain satisfactory sexual function in adult life.     

Testosterone and dihydrotestosterone levels in the epididymis, vas deferens and preputial gland of mice during sexual maturation

The levels of testosterone (T) and dihydrotestosterone (DHT) in the epididymis, vas deferens and preputial gland were assessed in mice from 1 to 90 days. The weight increase of these 3 organs was proportionately greater than that of the whole body until 50 or 60 days, and they attained their adult histological appearance approximately 20 days prior to puberty. Expressed in ng/g, the concentration of androgens (T+DHT) in the epididymis (14.3 to 36.5), vas deferens (6.6 to 24.0) and preputial gland (1.5 to 4.7) were higher than in plasma (0.2 to 3.6 ng/ml). The concentration of either androgen varied little during sexual maturation and was not correlated with circulating levels. The highest concentration of androgen (T+DHT) was observed at birth suggesting that the neonatal period is crucial for development of the accessory sexual organs. In the epididymis and preputial gland T was the predominant androgen during the infantile phase of development, whilst DHT predominated thereafter. In the vas deferens concentrations of T were always equal to or higher than those of DHT. These results suggest that the ability of the accessory sexual organs to accumulate androgens appears to be more important than the circulating concentration of androgens in determining their growth and differentiation.     

Postweaning exposure to gossypol results in epididymis-specific effects throughout puberty and adulthood in rats

Gossypol, a yellow pigment found in cottonseeds, well known for its antifertility properties in animals, has been used as a contraceptive by men. The aims of this work were to evaluate the effects of gossypol throughout sexual development of male rats and to provide additional data to clarify the target site or sites of this compound in the male reproductive system. Gossypol (15 mg/kg per day) was given to animals from weaning through prepuberty (41 days), early puberty (51 days), puberty (61 days), and sexual maturity (91 days). Ventral prostate weight and fructose levels were similar in control and treated rats, suggesting that androgen levels were normal. No histological effects on the testis were detected, but there was a significant decrease in the sperm concentration in the cauda epididymidis of gossypol-treated animals killed at 61 and 91 days, as well as a significant increase in abnormal sperm in the vas deferens of treated animals. Moreover, the histology of the cauda epididymidis of the rats treated throughout puberty (ie, until days 51 and 61) showed a great number of round bodies in the lumen of the epididymis. These structures stained for the epididymis-specific protein E. Collectively, the data demonstrate that the epididymis is a target of gossypol when postweaning exposure extends throughout pubertal development, and that whereas more subtle histological effects commence around puberty, indicators reproductive competence are compromised in adulthood.     

Pre- and postnatal testosterone administration induces proliferative epithelial lesions with neuroendocrine differentiation in the dorsal lobe of the rat prostate.

BACKGROUND: Androgens are implicated in the pathogenesis of prostatic carcinoma. We have elucidated the role of pre- and postnatal testosterone administration in the occurrence of proliferative lesions as well as neuroendocrine (NE) cells in the rat prostatic complex. METHODS: Female rats were given a single dose of 9 mg testosterone enantate i.m. on day 15 of pregnancy; it gave a high testosterone exposure to the fetus in the early organogenetic period of the rat prostatic complex. One group of the male offspring was followed without further testosterone treatment; a second group received testosterone only in the pubertal period; a third group was given testosterone from puberty and throughout life (46 weeks). These groups were compared to parallel groups (1A-1C) of male offspring without a testosterone supplement in pregnancy. RESULTS: The serum testosterone concentrations in the rats receiving testosterone were significantly higher than those of control rats. Histopathologically, the testosterone-induced proliferative lesions, mainly hyperplastic, were almost exclusively located in the dorsal lobe. Chromogranin A-immunoreactive (CgA-IR) cells were rarely found normally, but occurred more often in the proliferative lesions (P < 0.001). CONCLUSIONS: The incidence of proliferative lesions in rats exposed to testosterone only in puberty was comparable to the incidence found in those rats receiving testosterone in puberty and throughout life. This finding may have clinical implications for young athletes, who use testosterone as an anabolic drug. The occurrence of CgA-IR cells increased in proliferative lesions in the dorsal lobe of the rat prostatic complex.     

Androgens and male fertility

Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicle, prostate and the penis. Furthermore, androgens are needed for puberty, male fertility and male sexual function. High levels of intratesticular testosterone, secreted by the leydig cells, are necessary for spermatogenesis. Intratesticular testosterone is mainly bound to androgen binding protein and secreted into the seminiferous tubules. Inside the sertoli cells, testosterone is selectively bound to the androgen receptor and activation of the receptor will result in initiation and maintenance of the spermatogenic process and inhibition of germ cell apoptosis. The androgen receptor is found in all male reproductive organs and can be stimulated by either testosterone or its more potential metabolite dihydrotestosterone. Severe defects of the androgen receptor may result in abnormal male sexual development. More subtle modulations can be a potential cause of male infertility. Treatment of an infertile man with testosterone does improve spermatogenesis, since exogenous administrated testosterone and its metabolite estrogen will suppress both GnRH production by the hypothalamus and Luteinising hormone production by the pituitary gland and subsequently suppress testicular testosterone production. Also, high levels of testosterone are needed inside the testis and this can never be accomplished by oral or parenteral administration of androgens. Suppression of testosterone production by the leydig cells will result in a deficient spermatogenesis, as can be seen in men taking anabolic-androgenic steroids. Suppression of spermatogenesis by testosterone administration is also the basis for the development of a male contraceptive. During cytotoxic treatment or irradiation suppression of intratesticular testosterone production cells may prevent irreversible damage to the spermotogonial stem cells.     

Phytoandrogenic properties of Eurycoma longifolia as natural alternative to testosterone replacement therapy

The testosterone deficiency syndrome (TDS) is characterised by numerous symptoms, including low libido, increased fat mass, fatigue, erectile dysfunction or osteoporosis, and up to 80% of men will experience some kind of ageing males' symptoms. This is caused by the age‐depending decline in serum testosterone levels with concentrations being about 40–50% lower in men older than 60 years compared with young men. This significant decline in testosterone levels is further closely linked with medical conditions such as obesity, metabolic syndrome, diabetes or hypertension. The conventional way of treating TDS is the testosterone replacement therapy (TRT), for which preparations are on the market. Apart from the beneficial effects of TRT, significant adverse side effects have been described, and prostate cancer (PCa) as absolute contraindication is debated. Eurycoma longifolia (Tongkat Ali; TA) is natural alternative to TRT and has been shown to restore serum testosterone levels, thus significantly improving sexual health. This includes significant positive effects on bone health and physical condition of patients. In addition, a significant antihyperglycaemic effect and cytotoxicity against PCas cells has been shown. Thus far, at therapeutic concentrations, no significant side effects of the treatment were obvious. Therefore, TA might be a safe alternative to TRT.     

Evolution of somatic and germ cell populations after busulfan treatment in utero or neonatal cryptorchidism in the rat

Summary.  In order to elucidate the respective effects of depletion of germ cells and of increase in testicular temperature, rats of the same Wistar strain were rendered experimentally bicryptorchid or sterilized by a busulfan injection in utero and compared to control animals. In both models, germ cells were depleted but numeric evolution and functions of somatic cells differed. The aim of that work was to compare the numeric evolutions of testicular somatic and germ cells to their respective functions in each model before puberty and in adult rats of the same strain. Serum concentrations of FSH, LH and testosterone were compared at 20, 40 and 110 days of age. Histological analyses of Sertoli and germ cells in the seminiferous tubules and of Leydig cells in the intertubular tissue were performed before puberty and at adulthood. Testosterone serum concentrations were depleted in both models starting at 40 days of age and more in busulfan-treated rats. Both FSH and LH levels were increased from 20 days onwards in experimental rats. Additional cryptorchidism in busulfan-treated rats depressed the serum testosterone concentration. At 17 days of age, the cryptorchidism do not modify somatic or germ cell populations while busulfan treatment has induced a decrease of both these populations. Conversely, the cross sectional area of the somatic testicular cells was not affected whatever the treatment. In adult testes of busulfan-treated and cryptorchid rats, the total numbers of Sertoli and Leydig cells and of germ cells per testis were decreased. The cellular size of the perivascular Leydig cells was not modified by any of the treatments whereas the size of the Sertoli cells was reduced.
In conclusion, in both models the absence of germ cells induces a decrease in Sertoli cell function, while the increase in testicular temperature provokes degeneracies of Sertoli and germ cells in the seminiferous tubules of the rat.     

Changes in the secretion of ABP into testicular interstitial fluid with age and in situations of impaired spermatogenesis

Androgen-binding protein (ABP) was measured in serum and testicular interstitial fluid (IF) from rats during sexual maturation or in adult rats in which impairment of spermatogenesis had been induced by (i) testosterone withdrawal following Leydig cell destruction, (ii) local heating (43 degrees C) of the testes for 30 min or (iii) induction of unilateral cryptorchidism (UCD). The changes observed were related to the IF levels of testosterone and, in most instances, to the serum levels of FSH. The levels of ABP in serum and IF decreased together with age, being highest at 30 days, falling steeply by 40 days and then slowly but progressively up to 100 days of age. A similar pattern was observed for serum FSH, except that the initial fall occurred beyond 40 days of age. Treatment with EDS or exposure to local heating caused comparable reductions in testicular weight (25-30% by 7 days after treatment, 50% by 21-28 days) and raised the serum levels of FSH. In both groups the levels of ABP in IF were increased by two- to three-fold while the levels of testosterone were either reduced markedly (EDS-treatment) or remained unchanged (local heating). In rats made UCD for 60 days, the weight of the abdominal testis was reduced by 75%, compared with the contralateral scrotal testis, while the IF levels of ABP and testosterone were significantly increased (55%) and decreased (90%), respectively. Short-term (3 days) deprivation of testosterone in adult rats, following immunoneutralization of LH, was without significant effect on IF levels of ABP. It is concluded that ABP secretion into IF is increased in situations of subnormal (or sub-adult) numbers of germ cells and this is usually associated with high levels of FSH. Measurement of ABP levels in IF should prove of value for the monitoring of Sertoli cell function in vivo and may be of diagnostic use for the detection of changes in germ cell numbers.     

Effect of prenatal vitamin D (calcitriol) exposure on the growth and development of the prostate.

BACKGROUND: We previously found that in the absence of testosterone (T), calcitriol promotes proliferation of normal prostatic stroma, while in the presence of T, it has a differentiating effect on prostatic epithelium. The present study was conducted to determine the effect of calcitriol exposure in utero on the postnatal development of the normal prostate. METHODS: Pregnant rats were injected subcutaneously with either 1.25 microg of calcitriol or vehicle alone on alternate days till delivery. Calcitriol-exposed and control pups were sacrificed at age 25 days (prepuberty), 63 days (postpuberty), or 102 days (adults), and their prostates and seminal vesicles were harvested and weighed. RESULTS: Pups prenatally exposed to calcitriol and sacrificed before puberty (25 days) had a 35% greater mean prostatic weight than controls (0.0314 vs. 0.0422 g, P < 0.007), and calcitriol-exposed adult rats (102 days) had a 68% greater mean prostatic weight than controls (0.1365 vs. 0.2304 g, P < 0.005). No differences were observed in seminal vesicle weights, and in serum calcium and testosterone levels. A disproportionately high mortality rate from sudden death (71%) was observed at puberty in uncastrated male rats prenatally exposed to calcitriol. CONCLUSIONS: These findings suggest that high-dose calcitriol exposure in utero may uniquely influence subsequent prostatic growth. Nonandrogenic steroids such as calcitriol may also be involved in genetic imprinting of the prostate.     

长期大量饮酒对大鼠阴茎组织结构和功能的影响

目的探讨长期大量饮洒对大鼠阴茎组织结构和功能的影响。方法将30只雄性大鼠随机分为对照组，20％酒精剂量组和40％酒精剂量组。分别以生理盐水，20％和40％食用酒精各2ml给大鼠灌胃，每日1次。3个月后，观察各组大鼠的性行为和药物诱发阴茎勃起的情况；用酶放大物理发光仪测定各组大鼠血清睾酮的含量；对阴茎平滑肌三色改良法染色，并利用图象分析管理系统，分别计算各组大鼠阴茎平滑肌的目标总面积和面密度。结果与对只照组相比，20％酒精剂量组大鼠性行为受到抑制（P〈0．05），大鼠血清睾酮含量降低（P〈0．05）；40％酒精剂量组人鼠性行为，药物诱发阴茎勃起实验均受到抑制（P〈0．05），血清睾酮含量和平滑肌细胞数量减少。结论大鼠长期大量饮洒后性功能障碍，其机制与血浆睾酮含量降低，阴茎海绵体平滑肌成分减少有关。     

Effect of neonatal treatment of rats with potent or weak (environmental) oestrogens,or with a GnRH antagonist,on Leydig cell development and function through puberty into adulthood

This study addressed whether reduced Sertoli cell number or manipulation of the neonatal hormone environment has an influence on final Leydig cell number per testis in the rat, by applying neonatal treatments known to affect these parameters, namely administration of a GnRH antagonist (GnRHa) or diethylstilboestrol (DES, in doses of 10, 1 or 0.1 microg per injection). The effect of treatment with either of two 'environmental oestrogens', bisphenol-A (Bis-A) or octylphenol (OP), was also evaluated. Leydig (3beta-hydroxysteroid dehydrogenase immunopositive) cell development and function (plasma testosterone levels) were studied through puberty into adulthood. Treatment with GnRHa impaired testis growth, Leydig cell (nuclear) volume per testis and testosterone levels during puberty, when compared with controls, but final Leydig cell volume/number in adulthood was comparable with controls. As adult testis weight was reduced by 45% in GnRHa-treated rats, the percentage Leydig cell volume per testis was approximately double (p < 0.01) that in controls, and also at day 35. Testosterone levels in adulthood in GnRHa-treated rats were lower (p < 0.01) than in controls but were within the lower end of the normal range. Treatment with DES caused largely dose-dependent suppression of testis growth, Leydig cell (nuclear) volume per testis and testosterone levels up to day 35. Although by adulthood, Leydig cell volume/number per testis was comparable with controls in DES-treated rats, testosterone levels remained grossly subnormal. Neonatal treatment with either Bis-A or OP had little consistent effect on any of the parameters studied except that both treatments significantly elevated testosterone levels on day 18, as did treatment with DES-0.1 microg. The present findings are interpreted in the context of what is known about the hormonal regulation of Leydig cell development. These lead to the conclusion that final Leydig cell number per testis is not determined by the number of Sertoli cells per testis and appears not to be influenced in any major way by gonadotrophins, androgens or oestrogens in the first 2 weeks of postnatal life. This implies that adult Leydig cell number may be determined prior to birth.