Accessory Organ Weights Research Articles

Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention.

Arsenic (As) is a poisonous metalloid that is toxic to both humans and animals. Drinking water contamination has been linked to the development of cancer (skin, lung, urinary bladder, and liver), as well as other disorders such as diabetes and cardiovascular, gastrointestinal, neurological, and developmental damage. According to epidemiological studies, As contributes to male infertility, sexual dysfunction, poor sperm quality, and developmental consequences such as low birth weight, spontaneous abortion, and small for gestational age (SGA). Arsenic exposure negatively affected male reproductive systems by lowering testicular and accessory organ weights, and sperm counts, increasing sperm abnormalities and causing apoptotic cell death in Leydig and Sertoli cells, which resulted in decreased testosterone synthesis. Furthermore, during male reproductive toxicity, several molecular signalling pathways, such as apoptosis, inflammation, and autophagy are involved. Phytonutrient intervention in arsenic-induced male reproductive toxicity in various species has received a lot of attention over the years. The current review provides an in-depth summary of the available literature on arsenic-induced male toxicity, as well as therapeutic approaches and future directions.

Histomorphometric changes in the ovaries of thymectomized guinea pigs

Hypothalamic-pituitary-gonadal axis function is necessary for maintaining proper female reproductive cycle. This study aimed to evaluate the ovarian histomorphometric and histoarchitectural changes in neonatal, prepubertal and pubertal thymectomized female guinea pigs. A total of 30 female guinea pigs, sham-operated (n-5) and thymectomized (n-5) were studied in each group. The diameter and number of ovarian follicles among the thymectomized and sham operated female guinea pigs during estrus phase of estrous cycle was compared. Gonadal and accessory reproductive organs weights and microscopic features were studied in the sham operated guinea pigs and thymectomized. There were statistically significant changes in the number and diameter of follicles in the ovary in neonatal thymectomized female guinea pigs, but no significant changes were observed in prepubertal and pubertal female guinea pigs. Neonatal thymectomized female guinea pigs showed significant changes in their weight as well as changes in the microscopic features including reduced thickness of myometrium of uterus and less mucosal folding in the fallopian tube compared to the sham-operated group. But prepubertal and pubertal thymectomy did not affect the weight and microscopic features of gonads and accessory reproductive organs. Depending on the time of thymectomy, these results indicate morphological changes in the ovaries after thymectomy in females.

Preclinical aphrodisiac investigation of ethanol extract of Flueggea leucopyrus Willd. leaves

Sexual dysfunction is a widely found disorder worldwide now a day because of busy lifestyle and stress. Management of disease is somewhat difficult because of cost and shortage of effective treatment. In the present paper authors have investigated effect of ethanolic extract of Flueggea leucopyrus Willd. leaves as aphrodisiac potential on albino rats. The dried leaves of plant were extracted by cold maceration method using ethanol. It was investigated for in vivo aphrodisiac activity. Plant extract was administered at doses 200 and 400 mg/kg body weight for 45 days. The effect of extract on general mating behavior, potency test, morphological studies, organ weight and sperm motility were tested. The results were compared with standard reference sildenafil citrate. The acute toxicity of the drug extract was also checked. On oral administration of ethanol extract 200 and 400 mg/kg doses on 15th, 30th and 45th day of treatment in all treated groups significantly increased intromission latency, mounting frequency, ejaculatory latency and significantly decreased intromission latency, mounting latency, inter intromission interval and post ejaculatory interval. Test for potency showed significant increase in long flips, quick flips and erections. In all experimental animals morphological study showed significant increase in main and accessory reproductive organs weight and sperm motility. As compared to the control the prolonged treatments for all treated groups were highly effective. This showed that aphrodisiac activity has been shown by ethanol extract but it is less than the standard. The present study showed that ethanol extract of Flueggea leucopyrus Willd. leaf increase sexual behavior in rats. Thus it supports the claim for this drug as an aphrodisiac.

EFFECTS OF AQUEOUS STEM BARK EXTRACT OF XYLOPIA AETHIOPICA ON THE REPRODUCTIVE FUNCTIONS OF MALE RATS

Objective: The sexual stimulatory effect of aqueous stem bark extract of Xylopia aethiopica which is commonly used traditionally for the treatment of fertility-related problems in males is reported in this work.Methods: The present study investigated the effect of 14 d oral administration of 1 ml/kg distilled water (control), 100, 200 and 300 mg/kg of body weight of the stem bark extract on some fertility parameters of the Swiss male rats. So, all the target organs (testis, epididymis, vas deferens, seminal vesicle and prostate) were weighed. The sperm motility and sperm count in testis, epididymis and vas deferens were determined. Serum and tissue protein, as well as cholesterol, were evaluated. The serum testosterone level was also assessed.Results: The extract did not produced significant change in the mobility of sperm, the sperm count in vas deferens, the relative weight of body and accessory organs at all doses. The daily sperm production (DSP) and the weight of prostate significantly increased at a dose of 100 mg/kg (p<0.01) while the sperm count in cauda epididymis increased at a dose of 200 mg/kg. The testicular and serum cholesterol significantly increased (p<0.001) at the dose of 100 mg/kg whereas the testicular and serum proteins increased (p<0.001) at the dose of 200 mg/kg. The serum testosterone level increased following 14 d of treatment (p<0.01) at the dose of 100 mg/kg.Conclusion: The results suggest that Xylopia aethiopica may have the potentials of being developed into a male fertility enhancing drug.

Androgenic effects of aqueous and methanolic extracts of Ficus asperifolia in male Wistar rats

BackgroundAndrogen deficiency is a clinical syndrome resulting from the inability of the testes to produce physiological levels of testosterone due to a disturbance occurring at one or more levels of the hypothalamic-pituitary-testicular axis. The present study was undertaken to evaluate the androgenic properties of aqueous and methanolic extracts of Ficus asperifolia on normal and castrated immature rats.MethodsNormal rats were treated either per os with aqueous or methanolic extract of Ficus asperifolia (100 mg/kg or 500 mg/kg b.w.), distilled water (10 ml/kg b.w.), 5% Tween 80 (10 ml/kg b.w.) or subcutaneously with testosterone propionate (0.5 mg/kg b.w.). Castrated rats were treated with plant extracts (100 mg/kg b.w. or 500 mg/kg b.w.) alone or with the co-administration of plant extracts and testosterone propionate (s.c., 0.5 mg/kg b.w.) or bicalutamide (2 mg/kg b.w. per os). Animals were treated once a day during four weeks. Body weight growth and relative sexual organ weights were recorded at the end of each treatment. Some biomedical parameters were measured in the plasma (proteins, cholesterol), testes (cholesterol) and epididymis (proteins).ResultsIn normal rats, Ficus asperifolia significantly (p < 0.05) increased the relative weights of the testes and all sexual-dependent organs whereas total testicular cholesterol concentration was significantly (p < 0.05) decreased. In castrated groups, treatment with Ficus asperifolia was followed by an increase in the sexual organ weights, epididymal protein and prostatic acid phosphatase concentrations. The co-administration of testosterone and plant extracts significantly (p < 0.05) increased the weight of accessory sexual organs and epididymal protein contents. In the presence of bicalutamide (an anti-androgen), the sexual stimulating activity of Ficus asperifolia was diminished with remarkable effects on vas deferens weight (p < 0.05), plasma (p < 0.01) and epididymal (p < 0.05) protein contents.ConclusionFicus asperifolia possesses androgen-like activity through possible stimulation of cytoplasmic and/or nuclear receptors by the bioactive compounds found in its extracts.

Chinese herbal medicine enhances sexual function and c-Fos/nNOS expression in the nucleus accumbens of orchidectomized rats

ObjectiveTo determine whether the central nervous system is involved in the effect of Chinese herbal medicine on sexual function recovery in orchidectomized rats. MethodsOrchidectomized rats were administered intragastrically with a decoction of “kidney-nourishing” Chinese herbal medicine once per day for 28 days. Accessory genital organ weight, plasma testosterone, and mating behavior were investigated. The expression of c-Fos and neuronal nitric oxide synthase (nNOS) in neuronal cells in the nucleus accumbens (NAc) was analyzed by immunohistochemistry. ResultsThere was a decrease in accessory genital organ weight, plasma testosterone, and sexual behavior, as well as a low number of c-Fos-positive cells and a large nNOS-positive cell area in orchidectomized rats. Administration of the herbal medicine increased accessory genital organ weight, testosterone level, mating behavior, and c-Fos-positive cell number, while it decreased the nNOS-positive cell area in orchidectomized rats. ConclusionAn increase of plasma testosterone after administration of “kidney-nourishing” herbal medicine might contribute to the elevated sexual function and activity in orchidectomized rats. In addition, a central nervous system mechanism, such as the functional alteration of NAc, might be involved.

Effects of Tetracycline on Body Weight and Accessory Reproduc-tive Organ Weights (Prostate Gland and Seminal Vesicle) of Adult Male Wistar Rats

Effects of Tetracycline on Body Weight and Accessory Reproduc-tive Organ Weights (Prostate Gland and Seminal Vesicle) of Adult Male Wistar Rats

Synthesis of CdS Nanoparticle and Reveal Its Effect on Reproductive System of Male Albino Rats

This is a controlled research laboratory study (conducted in the research laboratory of the University of Rajasthan) which shows synthesis of CdS nanoparticle (NPs) and its effects on male reproductive system. Albino Wistar male rats (Rattus norvegicus), healthy fertile 3–4 months old weighing about 150–180 g were used for experimentation. NPs synthesis by chemical method and injected intra-peritoneal in healthy fertile male rats at the dose level of 2.5 mg rat−1 day−1 for 30 days. XRD and TEM analysis of NPs were performed for size measurement. Animals were killed 24 h after withdrawal of treatment, and sperm, haematological, serum, tissue biochemistry, and histopathological analyses were performed. NPs were synthesised and their size confirmed by XRD-TEM image. Sperm analysis altered, hormonal, biochemical, and histological changes support its anti-spermatogenic effect on reproductive organ. XRD pattern and TEM observation showed size of NPS which was estimated at 20 nm. Decrease in sperm density and motility, fertility index, testes and accessory organ weight, tissue protein, and glycogen contents in testes were observed. Increased cholesterol level and decrease testosterone level showed its adverse effect on fertility. Histological degradation in testes is clearly visible. No significant alteration in body and vital organs weight was found. NPs were synthesised successfully and revealed contraceptive activity in male rats.

Evaluation of reproductive toxicity in male rats treated with novel synthesized ruthenium(II) and gold(I)-NHC complexes

In this study, we aimed to determine the reproductive toxicity in rat induced by ruthenium(II)-NHC (RuII) and gold(I)-NHC (AuI) complexes that have anticarcinogenic effects. For this purpose, 35 Sprague–Dawley rats were randomly divided into 5 equal groups. In control group, rats treated with saline, RuII, and AuI complexes were intraperitoneally given high (10 mg/kg) and low (5 mg/kg) doses to rats via a one-time administration. The animals were sacrificed, and testis tissues were taken on Day 10 of the drug administration for the determination of the biochemical, histopathological, spermatological, and hormonal parameters. It was determined that treatment group that was subjected to treatment using both RuII and AuI complexes significantly caused oxidative, histopathological, spermatological, and hormonal damage compared to control group. However, the sexual and accessory organ weight did not significantly change when compared to control. In addition, it was shown that AuI treatment generally caused more adverse effects than RuII treatment in a dose-dependent manner. In conclusion, when these synthesized compounds are used for the treatment of cancer, they could cause toxic effects on male reproductive system and lead to infertility. However, RuII complex is a more preferable option in cancer treatment, particularly in terms of user safety.

Effect of the ethanolic extract from Fagara tessmannii on testicular function, sex reproductive organs and hormone level in adult male rats

The effect of ethanolic extract of Fagara tessmannii, wide medicinal plants used on reproductive function in South Cameroon, was investigated in male rats. Twenty male sexually experienced rats (four groups) were orally treated with vehicle, 0.01, 0.1, 1 g kg(-1) BW per day of F. tessmannii (equivalent to 16.67 g, 33.33 g, 50 g, 66.66 g kg(-1) dry raw material) for 14 days, the upper limit dose without any clinical sign of toxicity was 2 g kg(-1). Fagara tessmannii extract negatively affected weight of accessory organs and significantly affected body weight gain at dose 1 g kg(-1) (P < 0.05) in treated rats. The weight of epididymis and seminal vesicle significantly decreased at low doses (0.01 g kg(-1)) while the prostate weight decreased at all doses (P < 0.05). The transit of spermatozoa in cauda epididymidis significantly increased at lower dose of 0.01 g kg(-1) (P < 0.05). In addition, F. tessmannii extract affected neither daily sperm production (DSP) and DSP per g nor sperm count in vas deferens and epididymis. The length of stages IX-I of the seminiferous tubule and serum testosterone level increased dose-dependently following 14 days of treatment (P < 0.05). The results suggest that F. tessmannii, 14 days after treatment, may improve spermatogenesis, testosterone level and sperm transit in cauda epididymidis but negatively impair reproductive organ activities.

Effects of intraperitoneal administration of Citral on male reproductive organs in the rat

Introduction: The aliphatic monoterpene 3, 7-dimethyl-2, 6-octadienal (Citral) is a flavour additive widely used in the cosmetic and food industries. It has been shown to have a negative impact on female fertility acting via hormone receptors. No data is available about the effects of Citral on the male reproductive system. Objective: This study was carried out to study the effects of Citral on body weight, weights of the testes, epididymis, seminal vesicles, prostate, liver and kidneys, hepatic enzyme levels, plasma testosterone level and haemoglobin concentration, red blood cell count, white blood cell count and packed cell volume. Materials and Methods: Mature male rats (n = 12) were given Citral at a dose of 300 mg/kg body weight in 1 mL of olive oil, by single intraperitoneal injection for 14 consecutive days. The control group was treated similarly with 1ml of olive oil alone. On day 15, organ weights, plasma testosterone levels, hepatic enzyme levels and haematological parameters were assessed. Results: There were no effects on the liver enzyme levels or on haematological parameters. Testicular and accessory reproductive organ weights and plasma testosterone levels were significantly reduced in the Citral treated group, compared with the controls (P Conclusion: Citral in a dose of 300mg/kg body weight in 1 ml of olive oil, by single intraperitoneal injection for 14 consecutive days in rats leads to reduction in weights of the testes, epididymis, seminal vesicles, prostate and plasma testosterone levels. doi: 10.4038/gmj.v13i1.891 Galle Medical Journal Vol.13(1) 2008 29-32

Effect of ETBE on reproductive steroids in male rats and rat Leydig cell cultures

These experiments were conducted to follow up on a report of testis seminiferous tubular degeneration in Fischer 344 rats treated with high doses of ethyl t-butyl ether (ETBE). Also, high doses of a related compound, methyl t-butyl ether (MTBE), had been shown to reduce circulating testosterone (T) in rats. Isolated rat Leydig cells were used to compare hCG-stimulated T production following exposure to ETBE, MTBE, and their common main metabolite, TBA. In addition, male Fischer 344 rats were gavaged daily with 600 mg/kg, 1200 mg/kg or 1800 mg/kg ETBE in corn oil ( n = 12) for 14 days, the 1200 mg/kg dose chosen for comparison with a prior 14-day MTBE gavage experiment. In cell culture experiments, TBA was more potent than either ETBE or MTBE, both of which caused similar inhibition of T production at equimolar concentrations. In the in vivo study, no significant plasma T reduction was seen 1 h after the final 1200 mg/kg ETBE dose, whereas 1200 mg/kg MTBE had significantly lowered T when administered similarly to Sprague–Dawley rats. Some rats treated with 1800 mg/kg ETBE had noticeably lower T levels, and the group average T level was 66% of corn oil vehicle control ( p > 0.05) with high variability also evident in ETBE-treated rats. 17β-Estradiol had been increased by 1200 mg/kg MTBE, and was elevated in the 1200 and 1800 mg/kg ETBE dose groups ( p < 0.05), both groups also experiencing significantly reduced body weight gain. None of these effects were seen with 600 mg/kg/day ETBE. No definitive evidence of androgen insufficiency was seen in accessory organ weights, and no testicular pathology was observed after 14 days in a small subset of 1800 mg/kg ETBE-treated animals. Like MTBE, ETBE appears to be capable of altering reproductive steroid levels in peripheral blood sampled 1 h after treatment, but only with extremely high doses that inhibit body weight gain and may produce mortality.

Evaluation of various doses of testosterone on accessory reproductive organs and plasma testosterone in intact and gonadectomized rhesus monkeys (Macaca mulatta).

The effect of 10 days i.m. treatment of testosterone propionate (TP) on plasma testosterone and accessory reproductive organs were studied in adult (6 to 6 1/2 kg) male rhesus monkeys, housed under natural light conditions using six different dose levels. The study was scheduled in the month of September and October. To maintain the weight of accessory reproductive organs and testosterone levels in castrates, different dose levels of exogenous testosterone propionate were required: 3.2 mg/d for seminal vesicles, 4.8 mg/d for ventral prostate and 3.2 mg/d for plasma testosterone titer. The levels of so-called "physiological" doses of exogenous testosterone varied for various target organs under consideration. TP at a dose of 0.4 mg/d had a depressing effect on plasma testosterone in intact monkeys. For higher doses, plasma testosterone increased roughly similarly in both intact and castrated monkeys. It suggests that with otherwise "physiological" doses of testosterone propionate, there is an almost complete blockage of endogenous testosterone secretion.

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

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.

Lycium barbarum polysaccharides: Protective effects against heat-induced damage of rat testes and H 2O 2-induced DNA damage in mouse testicular cells and beneficial effect on sexual behavior and reproductive function of hemicastrated rats

Lycium barbarum, a famous Chinese medicinal herb, has a long history of use as a traditional remedy for male infertility. Polysaccharides are the most important functional constituent in L. barbarum fruits. We systematically investigated the effect of L. barbarum polysaccharides (LBP) on rat testis damage induced by a physical factor (43 °C heat exposure), on DNA damage of mouse testicular cells induced by a chemical factor (H 2O 2), and on sexual behavior and reproductive function of hemicastrated male rats. The results showed that LBP provided a protective effect against the testicular tissue damage induced by heat exposure. When compared with negative control, a suitable concentration of LBP significantly increased testis and epididymis weights, improved superoxide dismutase (SOD) activity, and raised sexual hormone levels in the damaged rat testes. LBP had a dose-dependent protective effect against DNA oxidative damage of mouse testicular cells induced by H 2O 2. LBP improved the copulatory performance and reproductive function of hemicastrated male rats, such as shortened penis erection latency and mount latency, regulated secretion of sexual hormones and increased hormone levels, raised accessory sexual organ weights, and improved sperm quantity and quality. The present findings support the folk reputation of L. barbarum fruits as an aphrodisiac and fertility-facilitating agent, and provide scientific evidence for a basis for the extensive use of L. barbarum fruits as a traditional remedy for male infertility in China.

Effects of bisphenol A given neonatally on reproductive functions of male rats

Male Sprague–Dawley rats (Crj:CD (IGS) were treated neonatally with bisphenol A (BPA) to evaluate effects on reproductive parameters. Animals were given BPA subcutaneously in corn oil to dosages of 0.002–97 mg/kg body weight, or 0.9 mg/kg 17β-estradiol (E2) once a day from postnatal day (PND) 0 to PND 9. Preputial separation, copulatory rate, fertility rate, sperm analysis, serum testosterone levels, and gene expression in the testis were assessed. Males in the E2 group showed a decrease in testis weight and alterations of estrogen-mediated gene expression in the testis on PND 10, and by PND 150 incomplete preputial separation, decreases in the copulatory rate, testicular and accessory organ weights and number of sperm. In contrast, males in all BPA groups showed normal reproductive parameters. These results indicate that in male rats, BPA given during the neonatal period neither affected reproductive function nor evoked estrogen-mediated gene responses in the testis.

Male reproductive toxicity of four bisphenol antioxidants in mice and rats and their estrogenic effect

Male mice and rats were fed a diet containing four bisphenol antioxidants, 2,2'-methylenebis(4-ethyl-6-tert-butylphenol) (ME), 2,2'-methylenebis(4-methyl -6-tert-butylphenol) (MM), 4,4'-butylidenebis(3-methyl-6-tert-butylphenol) (BM), or 4,4'-thiobis(3-methyl-6-tert-butylphenol) (TM) at levels of 0.06-0.25% for 2 months. BM and TM decreased epididymal, seminal vesicular, prostate and preputial weights, and injured seminiferous tubules in mice in a dose-dependent fashion. BM and TM also reduced sex accessory organ weights and sperm production capacity in rats, but MM and ME were more toxic to rats than BM and TM. ME and MM did not bind ERalpha up to 10(-3) M, while BM and TM competitively bound ERalpha against beta-estradiol (E2). Fifty percent inhibitory concentrations (IC50 s) of BM, TM, and bisphenol A (positive control) against E2-binding were 7.3 x 10(-6) M, 1.8 x 10(-5) M, and 1.4 x 10(-5) M, respectively. When ovariectomized (OVX) mice were sc administered TM at doses of 60 and 300 mg/kg/day for 4 days, or when OVX mice were fed BM in the diet at a level of 0.25% for 2 months, uterine weight was significantly increased. These results suggest that BM and TM are weakly toxic, possibly through an estrogenic mechanism to male reproductive organs in mice as well as rats, while MM and ME may be the direct testicular toxins in rats but not mice.

Reproductive and cytogenetic toxicity of metronidazole in male mice.

The purpose of this study was to examine the effects of metronidazole (500 mg/kg b.wt. daily by gavage for 14 consecutive days) on male fertility, haematopoiesis and genotoxic affinity. Mature male Swiss mice were treated with metronidazole and divided into 3 groups each with 10 animals, examined after 2 weeks, 1 and 2 months from the onset of drug administration. The results demonstrated that metronidazole significantly (P<0.05) decreased the weight of the testes, epididymides and accessory sexual organs (seminal vesicles and prostates) after one month from the onset of treatment. While accessory sexual organ weights were restored after 2 months from onset of treatment, the decrease in testes and epididymides weights persisted until 2 months later. The deleterious effects of metronidazole on reproductive organ weights might be due to a decrease in testosterone level after 2 weeks, and 1 and 2 months from the onset of treatment. Metronidazole induced a significant decrease in motile sperm and an increase in abnormal sperm after 1 month. The viability of sperm was normal after 2 months. Metronidazole induced anaemia characterized by decreased erythrocyte and leukocytic counts, haemoglobin content and haematocrit %. The ability of oral metronidazole administration to induce genotoxic damage in somatic cells of mice was evaluated using mitotic index, micronuclei and chromosomal aberration. A significant reduction in mitotic activity was observed two weeks from the onset of drug administration, restoration occurred after one month. A significant and persistence increase in the frequency of chromosomal aberration and micronucleus was observed at all periods of the experiment. In conclusion, the results of this study indicate that 1) metronidazole (500 mg/kg by gavage) for 14 days caused a harmful effect on male fertility in mice after one and two months from start of administration, 2) metronidazole induced anaemia after one month from start of administration, 3) metronidazole at this high dose level (3 times the therapeutic dose in mice) has the ability to induce genotoxic effects in somatic cells.

Puberty is delayed in male growth hormone receptor gene-disrupted mice.

The role of insulin-like growth factor-I (IGF-I) in the initiation of puberty and testicular function is poorly understood. Growth hormone (GH) receptor (R) gene-disrupted mice or GHR gene "knockouts" (GHR-KO) are GH resistant and IGF-I deficient. To assess whether the age of sexual maturation is affected by the absence of IGF-I, various parameters of sexual development including testicular and accessory reproductive organ weights, balanopreputial separation, germ cell development, and intratesticular testosterone levels were determined in normal and GHR-KO mice between the ages of 25 and 60 days. In addition, at 36 days of age, the testosterone response to luteinizing hormone (LH) treatment was assessed in these mice. The results indicate that the balanopreputial separation was delayed 5 days, and a significant increase in the weights of the seminal vesicles (SV) occurred later in GHR-KO mice than in normal animals (between 30 and 35 days and between 35 and 40 days, respectively). Also, the weights of testes and epididymii were significantly reduced in GHR-KO mice. The intratesticular testosterone levels and the testosterone response to LH treatment were attenuated in GHR gene-disrupted mice. Furthermore, elongated spermatids appeared later in the testes of GHR-KO mice than in the testes of normal mice. These results suggest that the absence of IGF-I secretion delays the normal course of sexual maturation in male GHR-KO mice, indicating that IGF-I plays an important role in the initiation of puberty in male mice.

Hormone-like behavioral effects of levonorgestrel and its metabolites in the male rat

Levonorgestrel (LNG), a contraceptive progestin, exhibits, besides its progestational activity, other hormone-like effects at the peripheral level. To assess whether LNG and its metabolites exert androgenic and/or estrogenic actions at the central nervous system (CNS), their effects on male sexual behavior in castrated rats were examined. LNG, 5α-dihydro LNG (5αLNG), and the 3α,5α- and 3β,5α-tetrahydro derivatives of LNG (3αLNG and 3βLNG, respectively) were administered for 3 weeks either alone (1000 μg/day) or in combination (300 μg/day) with 5α-dihydrotestosterone (DHT, 300 μg/day) or with estradiol-17β (E 2, 5 μg/day). Copulatory behavior was assessed twice per week and sex accessory organs weights recorded at the end of treatments. LNG restored full copulatory behavior comparable to that of testosterone treated animals, although with a slight delay, whereas 5αLNG induced male sexual behavior in a significantly lower number of subjects. 3βLNG and 3αLNG induced mounting but failed to restore intromission and ejaculation. Combined LNG+E 2 treatment fully activated mounting and intromission, but ejaculation was only partially restored. Combined 5αLNG+E 2 treatment and the combinations of 3αLNG or 3βLNG with E 2 were significantly less effective, activating fewer intromissions and ejaculations. 3αLNG and 5αLNG, in combination with DHT, restored male sexual behavior. LNG, but not its metabolites, induced a significant increase on the weight of sex accessory organs. The overall results demonstrated that high doses of LNG induce a potent androgen agonistic behavioral effect and that its A-ring reduction diminishes this potency and enables a shift towards a weak estrogen-like effect.