Doses Of Testosterone Propionate Research Articles

Testosterone ameliorated the behavioural deficits of gonadectomised rats and counteracted free radicals in a dosage-dependent manner

Testosterone deficiency may induce behavioural changes in individuals. Oxidative stress resulting from a redox imbalance may be implicated in the initiation and progression of neurobehavioural disorders. However, whether exogenous testosterone intervention in male gonadectomised (GDX) rats ameliorates oxidative stress and plays a neuroprotective role remains unknown. Therefore, we examined this hypothesis by performing sham or gonadectomy surgeries on Sprague–Dawley rats with or without supplementation with different doses of testosterone propionate (TP). Open field and Morris water maze tests were performed, the serum and brain testosterone levels, and oxidative stress markers were analysed. GDX and lower TP doses (0.5 mg/kg) induced reduced exploratory and motor behaviours, but impaired spatial learning and memory compared to Sham rats. Administration of physiological TP levels (0.75–1.25 mg/kg) to the GDX rats restored the behaviour observed in the intact rats. However, higher TP doses (1.5–3.0 mg/kg) induced increased exploratory and motor behaviours but impaired spatial learning and memory. These behavioural impairments were accompanied by a marked decrease in levels of antioxidant enzymes (superoxide dismutase and catalase) and an increase in lipid peroxidation levels in the substantia nigra and hippocampus. These findings indicate that TP administration can alter behavioural performance and induce memory and learning impairment, which may result from changes in redox homeostasis in male GDX animals.

Testosterone propionate improves motor alterations and dopaminergic damage in the reserpine-induced progressive model of Parkinson's disease

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder with a higher susceptibility to occur in men. Studies suggest that this susceptibility is related to the hormonal differences observed between men and women, being a risk factor for PD. In addition, testosterone supplementation has shown controversial results in animal models of PD and parkinsonian patients. This study evaluated the effect of chronic administration of testosterone propionate (TP) on motor behavior and neurochemical parameters in the reserpine-induced rat model of parkinsonism. Male Wistar rats received 15 injections of reserpine (RES – 0.1 mg/kg) every other day and were concomitantly treated with different doses (0.1, 1.0, or 5.0 mg/kg) of daily TP for 30 days. The rats were euthanized 48 h after the 15th injection of RES or vehicle. Brains were removed and subjected to Tyrosine hydroxylase (TH) immunohistochemistry. TP at 1.0 mg/kg reduced the damages caused by reserpine in the vacuous chewing and tong protrusion behaviors and prevented dopaminergic damage in the SNpc, VTA, and Striatum. TP at 5.0 mg/kg reduced the damages caused by reserpine in the catalepsy and tong protrusion behaviors, prevented the weight loss, and prevented dopaminergic damage in the VTA. Our results suggest that chronic administration of TP has a protective effect in a rat model of parkinsonism, improving motor alterations and dopamine depletion induced by RES.

Abnormalities in Microarchitecture and Reduced Mechanical Bone Strength in a Rat Model of Polycystic Ovary Syndrome

Evidence from the literature is contentious about the impact of polycystic ovary syndrome (PCOS) on the skeleton, suggesting a possible negative role of this condition on non-obese women. We investigated this hypothesis employing a well-characterized testosterone propionate (TP) rodent model of PCOS to address the consequences of androgenization on bone microarchitecture, histology, and mechanical strength. For this study, Wistar rats (n= 38) were divided in 4 groups: 1) “Control OVX” (single dose of corn oil s.c. at day 5 of life and ovariectomy at day 100, n=9); 2) “Control SHAM” (n=9); 3) “Androgenized OVX”(single dose of TP 1.25 mg s.c. at day 5 of life and ovariectomy at day 100, n=10); and 4) “Androgenized SHAM” (n=10). Full characterization of estrous cycles and weight was performed during growth, and all animals were euthanized at day 180. Successful ovariectomy was confirmed by neglected levels of serum estradiol. Endpoints evaluated include bone micro CT (femur and spinal column), bone histology (number of osteoclasts and osteoblasts in the femur), and mechanical tests. The study was approved by the local Ethics Committee. At the end of the study (day 180), Androgenized OVX rats were heavier than the other three groups. MicroCT Analysis: Androgenized SHAM rats exhibited a significantly higher trabecular mass in the spine (BV/BT) (mean + SEM) 49.21 + 2.42 % versus Control SHAM 36.42 + 1.39 % (Student T-test p=0.001). Following ovariectomy, BV/BT in Androgenized OVX was 40.4 + 2.83 % against 20.34 + 1.85 % in Control OVX (Student T-test p=0.0003). Lumbar trabecular thickness(μm) was also higher in Androgenized OVX (p=0.0065) as well the Trabecular number (n/mm)(p=0.0003). A similar increase in trabecular mass was observed in the femur. Androgenized SHAM rats had a significant higher BV/BT (%), trabecular thickness(μm), and decreased trabecular separation (p < 0.001). However, a significant reduction in cortical bone (thickness) was noted (Student T-test p=0.001). A histological study of the distal femur of Androgenized SHAM rats also show a significantly increased number of osteoclasts and decreased number of osteoblasts than Control SHAM (0< 001). When submitted to the mechanical test, Androgenized Sham rats presented a decreased strength (p<0.01) in relation to its controls. After ovariectomy, there was a reduction in bone in all oophorectomized groups. However, differently than the vertebral bones, no differences regarding bone mechanical strength or stiffness as well microCT values, or bone histology parameters were noted in the femur of Control OVX or Androgenized OVX. Our results suggest that androgenization in a rodent model of PCOS leads, at the same time, to a generalized increase in trabecular (cancellous) bone mass (especially in the spine), associated with a reduced cortical bone mass and decreased strength of the femur.

Testosterone replacement causes dose-dependent improvements in spatial memory among aged male rats

Testosterone has been shown to have dose-dependent effects on spatial memory in males, but the effects of aging upon this relationship remain unclear. Additionally, the mechanism by which testosterone regulates memory is unknown, but may involve changes in brain-derived neurotrophic factor (BDNF) within specific brain regions. We tested the effects of age and testosterone on spatial memory among male rats using two spatial memory tasks: an object-location memory task (OLMT) and the radial-arm maze (RAM). Castration had minimal effect on performance on the RAM, but young rats (2 months) performed significantly fewer working memory errors than aged rats (20 months), and aged rats performed significantly fewer reference memory errors. Both age and castration impaired performance on the OLMT, with only the young rats with intact gonads successfully performing the task. Subsequent experiments involved daily injections of either drug vehicle or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.00 mg/rat) given to castrated aged males. On the RAM, a low physiological dose (0.125 mg) and high doses (0.500–1.000 mg) of testosterone improved working memory, while an intermediate dose (0.250 mg) did not. On the OLMT, only the 0.250 mg T group showed a significant increase in exploration ratios from the exposure trials to the testing trials, indicating that this group remembered the position of the objects. Brain tissue (prefrontal cortex, hippocampus, and striatum) was collected from all subjects to assay BDNF. We found no evidence that testosterone influenced BDNF, indicating that it is unlikely that testosterone regulates spatial memory through changes in BDNF levels.

Effects of testosterone dose on spatial memory among castrated adult male rats

Previous research on the activational effects of testosterone on spatial memory has produced mixed results, possibly because such effects are dose-dependent. We tested a wide range of testosterone doses using two spatial memory tasks: a working-reference memory version of the radial-arm maze (RAM) and an object location memory task (OLMT). Adult male Sprague-Dawley rats were castrated or sham-castrated and given daily injections of drug vehicle (Oil Sham and Oil GDX) or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.000 mg T) beginning seven days before the first day of behavioral tests and continuing throughout testing. For the RAM, four arms of the maze were consistently baited on each day of testing. Testosterone had a significant effect on working memory on the RAM, with the Oil Sham, 0.125 mg T, and 0.500 mg T groups performing better than the Oil GDX group. In contrast, there was no significant effect of testosterone on spatial reference memory on the RAM. For the OLMT, we tested long-term memory using a 2 h inter-trial interval between first exposure to two identical objects and re-exposure after one object had been moved. Only the 0.125 and 0.500 mg T groups showed a significant increase in exploration of the moved object during the testing trials, indicating better memory than all other groups. Testosterone replacement restored spatial memory among castrated male rats on both behavioral tasks, but there was a complex dose-response relationship; therefore, the therapeutic value of testosterone is likely sensitive to dose.

Співвідношення основних фракцій ліпідів у жовчі щурів при дії тестостерону

У гострих дослідах на щурах-самцях із канюльованою жовчною протокою, які перебували під тіопенталовим наркозом (60 мг/кг), установлено, що ефективність дії внутрішньопортально введеного тестостерону пропіонату (0,7 мг/кг) проявляється поступово й тільки через 2–2,5 год реєструються достовірні суттєві зміни у співвідношенні основних фракцій ліпідів у жовчі піддослідних тварин, порівняно з контролем. У зв’язку з широким застосуванням препарату тестостерону пропіонату та з огляду на виявлені його ефекти на ліпідний склад жовчі при одноразовому внутрішньопортальному введенні доцільно дослідити вплив курсового застосування цього препарату на характеристики зовнішньосекреторної функції печінки.

Effects of Stimulation and Blockade of D2 Dopamine Receptors on the Behavior of Gonadectomized Male Rats

The present study aims to perform the comparative assessment of stimulation and blockade for D2-dopaminergic receptors in depression-like behavior in male rats with deficiency of androgen hormones. Two weeks after surgery, GDX rats began 14 days of treatment with vehicle, a low dose of testosterone propionate (0.5 mg/kg, s.c.), quinpirole (0.1 mg/kg, i.p.), sulpiride (10.0 mg/kg, i.p.), quinpirole plus testosterone propionate or sulpiride plus testosterone propionate. The animals were then tested in forced swimming test (FST) and the open field test (OFT). Quinpirole administered alone or in a combination with a low dose of testosterone propionate resulted in antidepressant-like effect in GDX rats in the FST. Repeated treatment of quinpirole and testosterone propionate profoundly increased antidepressant-like effect of the single substances they exert per se. Application of neither quinpirole nor quinpirole plus testosterone propionate led to any changes of behavioral reactions in GDX rats in the OFT, except increased grooming behavior. On the contrary, sulpiride treatment failed to alter depression-like behavior in GDX rats in the FST. In addition, sulpiride blocked the antidepressant-like effect of testosterone propionate in GDX rats and its combination with a low dose of testosterone propionate induced prodepressant-like effect in GDX rats. Co-administration of sulpiride with testosterone propionate or its single application increased frequency of rearing and grooming in GDX rats in the OFT. In summary, the results of the present study suggest that stimulation of D2-dopaminergic receptors results in antidepressant-like effect at androgen deficiency in male rats, while blockade of D2-dopaminergic receptors resulted in prodepressant-like effect.

Blockade of D2-like Dopamiergic Receptor Corrects Anxiety-like Behaviour in Gonadectomized Male Rats Treated with Low Dose of Testosterone

Several preclinical and clinical data suggest that DA, acting on D2-dopaminergic receptors, is one of the most important neuromodulators of fear and anxiety. On the other hand, both basic and clinical reports showing that steroid hormones are involved in the modulation of anxiety. The present work was devoted to the comparative analysis of behavioral and hormonal status in the gonadectomized (GDX) male rat chronically treated with high-selective D2-dopaminergic agonist or antagonist alone or in a combination with a low dose of testosterone propinate (TP). Two weeks after surgery, GDX male rats of 3-4 months age began 14 days of treatment with the vehicle, low dose of testosterone propionate (1.0 mg/kg, s.c.), D2-dopaminergic agonist, quinpirole (0.1 mg/kg, i.p.), D2-dopaminergic antagonist, sulpiride (0.1 mg/kg, i.p.), quinpirole plus testosterone propionate or sulpiride plus testosterone propionate. The animals were then tested in the elevated plus maze and the open field test. Sulpiride alone or in a combination with TP treatment significantly increased the time spent and number of entrees into the 'open” arms of the elevated plus maze in the GDX rats. The post-hoc test showed that in GDX rats treated with sulpiride, there was a significant increase in the frequency of rearing and grooming compared with the GDX rats. The results of this study demonstrate that sulpiride and testosterone propionate in GDX rats interact to exert an anxiolytic-like action and that each of these drugs can improve the effects of the other drug. This work was supported by RFBR grant ? 14-04-00795.

P.2.g.001 Stimulation of D2 dopaminergic receptor corrects depression-like behaviour in prenatally stressed gonadectomised male rats

Statement on the purpose of the study: Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioral alterations including impaired feedback mechanisms of the HPA axis, increased anxiety-/depressive-like disturbances and altered brain function of many neurotransmitter systems [1]. Several preclinical and clinical data suggest that DA, acting on D1/D2-like dopaminergic receptors, is one of the most important neuromodulators of despair behavior [2]. On the other hand, the activity of the dopaminergic neurotransmitter system is sensitive to modulation by the gonadal steroids [3]. The aim of this work was to study the effects of administration of D2 receptor agonist quinperole and D2 receptor antagonist sulpiride injected chronically for 14 days alone or in combination with low dose of testosterone propionate on depression-like behavior in adult prenatally stressed male rats. Methods: Initially, rat dams of Wistar strain were exposed to PRS during the last week of pregnancy. After delivery, prenataly stressed male offspring of 3−4 months age were subjected to gonadectomy. Two weeks after gonadectomy, prenatally stressed GDX male rats of 3−4 months age began 14 days of treatment with the vehicle, a low dose of testosterone propionate (1.0mg/kg, s.c.), D2-like dopaminergic agonist, quinpirole (0.1mg/kg, i.p.), D2-like dopaminergic antagonist, sulpiride (0.1mg/kg, i.p.), quinpirole plus testosterone propionate or sulpiride plus testosterone propionate. The animals were then tested in the forced swimming test (FST) and the open field test (OFT). The measurement of lutropine (LH) and testosterone (T) in the blood samples was performed by ELISA. Statistical processing of the received data was carried out with use of one-way ANOVA test and post-hoc test at p< 0.05. Results: The prenatally stressed GDX rats demonstrated the increased immobility time in the FST (p< 0.05). We found that quinpirole significantly decreased immobility time in the prenatally stressed GDX males. A combination of quinpeirole with a low dose of testosterone propionate induced more profound decrease of immobility time in the prenatally stressed GDX rats compared to the rats treated with quinpirole alone. On the contrary, sulpiride failed to modify depression-like behavior in the prenatally stressed GDX rats. In addition, sulpiride significantly blocked the antidepressant-like effect of testosterone propionate in prenatally stressed GDX rats. Thus, quinpirole alone or in combination with a low dose of testosterone propionate exerted antidepressant-like effect in prenatally stressed GDX rats, while the D2 receptor antagonist sulpiride produced depressant-like profile on GDX rats. Also, quinpirole in combination with low dose of testosterone propionate increased T levels, but decreased LH levels in the blood serum of GDX rats compared to the control group (p< 0.05). Conclusions: The results of this study demonstrate that quinpirole and testosterone propionate in prenatally stressed GDX rats interact to exert an antidepressant-like effect and that each of these preparations can improve action of the other drug. This study indicate that prenatal stress can be very important factor in efficacy for antidepressant treatment and limiting factor for using of antidepressants.

The Effects of Chronic Administration of Testosterone Propionate with or without Estradiol on the Sexual Behavior and Plasma Steroid Levels of Aged Female Rats

Low sexual desire concomitant with feelings of distress is reported in naturally and surgically menopausal women. A combination of estradiol (E2) and testosterone (T) restores sexual desire and interest in these women. The central mechanisms by which E2 and T act to restore desire are poorly understood. Here we examined the effect of chronic treatment with testosterone propionate (TP) administered by a sc SILASTIC brand capsule in aged ovary-intact female rats. Females were first treated with TP alone, followed by a second phase when TP was administered in combination with estradiol benzoate (EB; 10 μg) by sc injection 48 h prior to testing (EB+TP). Each phase consisted of 5 test days at 4-d intervals. Appetitive and consummatory female sexual behaviors were observed in bilevel chambers, and plasma E2 and T concentrations were measured with ELISA. Sexual solicitations and hops and darts were facilitated by the highest TP dose, and the lordosis quotient was increased by the two highest TP doses when administered alone, coinciding with an increase in plasma T, but those behavioral effects were not maintained across time. The lordosis quotient was inversely related to the TP dose in the EB+TP phase. These results suggest that the administration of TP by sc capsules to aged female rats facilitates appetitive and consummatory sexual behaviors; however, chronic treatment appears to be inhibitory. This is the first study to assess sexual behavior after SILASTIC brand implants of TP in the aged female rat. Additional research is needed to elucidate the mechanisms underlying the effects of T on female sexual function.

Applicability of lectin histochemistry in a test system with in ovo treatment for detecting androgenic and antiandrogenic effects of chemicals in Japanese quail (Coturnix japonica)

The aim of the current study was to examine whether analysis of the appearance of specific lectin-positive substances in the quail embryonic cloacal gland would be useful for evaluating the androgenic and antiandrogenic effects of chemicals. Fertilized Japanese quail eggs were injected with 0 to 75 µg of cyproterone acetate (CA), an antiandrogenic compound, on d 12 of incubation (d 12), followed by injection of 0 to 300 µg of testosterone propionate (TP) on d 13. Experimental groups consisted of a control group (corn oil injections on d 12 and 13), a TP-L group [corn oil and a low dose (L; 30 µg) of TP], a TP-H group [corn oil and a high dose (H; 300 µg) of TP], a CA-L + TP-H group [a low dose (L;7.5 µg) of CA + TP-H], and a CA-H + TP-H group [a high dose (H; 75 µg) of CA + TP-H]. The cloacal tissues were collected on d 16, processed into paraffin sections, and stained using 14 different biotinylated lectins. The Vicia villosa (VVA) lectin most strongly stained the developing cloacal glandular cells in TP-H. Western blotting analysis showed 1 VVA-positive band of approximately 75 kDa. The ratio of VVA-positive areas per unit square examined microscopically by image analysis was significantly greater in the TP-H group than in the control group in both males and females. The ratio was significantly decreased in the CA-L + TP-H and CA-H + TP-H groups compared with the TP-H group in both males and females. Furthermore, the ratio was smaller in females than in males within a TP-L or TP-H treatment group. These results suggest that lectin histochemistry on quail embryonic cloaca using VVA is useful for evaluating the androgenic and antiandrogenic effects of chemical compounds.

Testosterone treatment of pregnant rabbits affects sexual development of their daughters

The intrauterine position (IUP) may affect the sexual development of a female fetus in litter-bearing mammals. Females gestating between two males (2M) develop into masculinized adults compared to females without contiguous males (0M). Fetuses are known to secrete different types and amounts of steroid hormones during the prenatal period, and diffusing steroids may affect sexual differentiation of their neighbors, too. Exposure of elevated testosterone (T) levels generally results in masculinized anatomy and behavior in females of several rodent species. Our recent study showed that IUP-dependent masculinization is also present in the domestic rabbit, which shows large variation in sex related traits as adults. The aim of the present study was to test if the IUP effect in rabbits can be induced by exogenous testosterone treatment. By administering different doses of testosterone propionate (TP) to pregnant rabbits, and following anatomical and behavioral development of their female offspring, we obtained dose-dependent increase both in the anogenital distance (AGD) and chin-marking behavior of prenatal T exposed females. The effects of treatment corresponded to the variation due to intrauterine position in our previous study, namely, exposure to T of known external origin resulted in similar tendencies of masculinization in rabbit females as the in utero proximity to male siblings. Our results suggest that the IUP effects may have similar physiological bases across different mammalian taxa including Lagomorphs.

Pathophysiological changes associated with sustained delivery of DHT and TP by means of Hydroxyapatite (HA) delivery system

The objective of this study was to investigate the effect of various dosages of testosterone propionate (TP) and dihydrotestosterone (DHT) delivered in a sustained manner by means of hydroxyapatite lysine delivery system (HADS), on seminal vesicles as well as other vital organs. Adult male Sprague Dawley rats were randomly divided into eight equal groups (n=16). Rats in group I‐ III were implanted subcutaneously with HADS containing 200, 120, or 50 mg of TP. Rats in group IV‐IV were implanted subcutaneously with HADS containing 200, 120 or 50 mg of DHT. Group VII animals were implanted with empty HADS, and group VIII served as unimplanted controls. At the end of 1, 2, 3, and 6 months post‐implantation, four animals from each group were sacrificed and the seminal vesicles (SV), adrenal, heart, liver, and kidney were collected and evaluated. The results demonstrated the following: 1) SV weights were directly proportional to the dose of TP and DHT. 2) SV weights from animals implanted with 200mg TP were 3 fold greater than control. 3) No significant changes were observed in the weights of the spleen, kidney, liver and heart tissues. 4) In contrast to the other vital organs, the mean weight of the adrenal gland was slightly affected by high dosage of TP delivery compared to DHT and controls groups. 5) Cross sections of the seminal vesicles demonstrated that there was a decrease in the secretory epithelial cell height as well as an increase in papillary folding in all experimental groups. The results of this study suggest that TP and DHT are key factors in maintenance of secretory epithelium of the seminal vesicles.

OECD validation of phase‐3 Hershberger assay using the stimulated weanling male rat in Korea

The OECD has proposed a new, validated test guideline with the stimulated weanling male Hershberger assay to avoid the surgical castration step. In the present study, we assessed the relevance and reliability of the stimulated weanling Hershberger assay in four stages. All chemicals except for testosterone propionate (TP) were orally administered to sexually immature male rats of 22 days old for 10 days. The weights of four mandatory accessory sex organs, two additional reproductive tissues and optional systemic organs were evaluated. At the first two stages, TP, as reference androgen, significantly increased the weights of epididymides and accessory sex organs (ASO) at 1.0 mg kg(-1) and flutamide (FLU), as a positive anti-androgen control, decreased the TP-stimulated organ weights at 3.0 mg kg(-1). At stage 3, trenbolone (40 mg kg(-1)), an anabolic steroid, significantly increased ASO weights, and weak anti-androgens (DDE and linuron) decreased the TP-stimulated ASO weights at each high dose. The above results were confirmed in a blind test with coded substances provided by OECD. Compared with results from our previous castrated male assay, the intact weanling version is less sensitive than the castrated male version, in terms of a smaller response at the reference dose of TP or FLU. However, this study suggests that the stimulated weanling Hershberger assay can detect the effects of both potent and weak anti-androgens on androgen-producing and androgen-dependent tissues.

Differential Effects of Chronic Testosterone Treatment on the Onset of Puberty in Male Rats

Immature male rats were daily injected with 5 or 10 micrograms testosterone propionate (TP)/100 g b.w. from day 5 after birth through day 30 or through the day at which spermatozoa appeared in preputial smears (SpA). The age and body weight at preputial separation (PS) and SpA as well as the testes weight on the day of SpA were recorded. Reduced testicular weights as compared to the controls injected with oil were found in all experimental groups. Whereas daily injections of 5 micrograms TP/100 g b.w. did not alter the age and body weight at PS and SpA, administration of the higher TP dose from day 5 through day 30 resulted in highly significant delay of PS and SpA. This effect was almost completely abolished if treatment was continued to the day of SpA. In otherwise untreated males, however, injections of 10 micrograms TP/100 g b.w. from day 30 through the day of SpA did not advance the spontaneous onset of puberty. The findings suggest that slight elevation of the circulating testosterone level during infancy causes impairment of testicular functions resulting in retardation of spermatogenesis and, presumedly, long-lasting reduction of testosterone secretion. The effect can be abolished by substitution of testosterone during the late prepubertal phase, but spontaneous sexual maturation can probably not be accelerated in this way.

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.

Hormonal Regulation of Rat Testicular γ-Glutamyl-Transpeptidase “In Vivo” and “In Vitro”/Die hormonelle Regulation von testikulärer γ-Glutamyl-Transpeptidase bei Ratten “in vivo” und “in vitro”

The hormonal regulation of gamma-glutamyl transpeptidase (gamma-GTP), an enzyme marker of Sertoli cells, was studied in immature rats that received 50 micrograms/day of testosterone propionate (TP) during 6 days to suppress pituitary LH and FSH. Suppression of LH was monitored indirectly by the determination of intratesticular levels of testosterone and suppression of FSH by radioimmunoassay of serum FSH. Enzyme activity in the testis decreased in parallel to intratesticular testosterone suppression, and it did recover up to control values when animals received 500 micrograms/day of TP, a dose that was able to maintain intratesticular testosterone at normal levels. beta-glucuronidase, another enzyme marker of Sertoli cells, was not affected by these treatments. A significant decrease in gamma-GTP was detected 24h after significant suppression of intratesticular testosterone and it returned to control levels 2 days after increasing the dose of TP to 500 micrograms/day. Administration of FSH to rats with depletion of intratesticular testosterone was able to maintain testicular gamma-GTP at control levels. An stimulatory action of FSH could also be demonstrated in primary Sertoli cell cultures. It is concluded that testicular gamma-GTP is under the regulation of both androgens and FSH while beta-glucuronidase is not. Eventhough the function of gamma-GTP in the testis is not known, the key role that it plays in other tissues suggests that it might be important in the regulation of Sertoli cell-germ cell interactions.

Androgenic profile and genotoxicity evaluation of testosterone propionate and novel synthesized heterocyclic steroids

In this study, we tested the androgenic activity of three structurally promising novel synthesized heterocyclic steroids compared with testosterone propionate in male mice. Additionally, the possible genotoxic effects of the novel synthesized heterocyclic steroids in comparison with testosterone propionate on male mice using chromosomal analysis of somatic and germ cells as well as RAPD–PCR were investigated. Male mice were administered with two doses of testosterone propionate, pyridoandrostene derivative 4b, pyrimidinoandrostene derivative 9a and thienoandrostene derivative 12 (200 and 400 mg/kg b.w.) daily for 2 weeks. Results indicated that compounds 4b and 12 have androgenic activity as well as testosterone propionate. There were no significant differences in the frequencies of total chromosomal aberrations in both somatic and germ cells as well as no alteration in the DNA bands patterns between control, testosterone propionate and pyridoandrostene 4b treated animals. However, the pyrimidinoandrostene derivative 9a caused significant increase in the mean value of total chromosomal aberrations of both somatic and germ cells ( P ≤ 0.01) as well as enhanced the polymorphic bands patterns as compared to the control and the other tested compounds. On the other hand, thienoandrostene derivative 12 induced significant decrease in the mean values of chromosomal aberrations in both somatic and germ cells, decreased sperm morphological abnormalities, increased the sperm count and motility than control. Our data indicate that testosterone propionate; pyridoandrostene 4b and thienoandrostene derivative 12 have no genotoxic activity. However, pyrimidinoandrostene derivative 9a has genotoxic activity possibly due to a modulation of the different expression of the catalyzing enzyme systems which will be investigated in the nearly future.

Effects of androgen on embryo implantation in the mouse delayed-implantation model

To examine the effects of androgen on implantation and decidualization in the mouse delayed-implantation model. Experimental animal study. University research laboratory. Sexually mature female mice (Kunming White strain). Delayed and activated implantation; pseudopregnancy; embryo transfer (ET); E(2) assay; inhibitor. Effects of androgen on embryo implantation were determined by treating the mice under delayed implantation with different doses of testosterone propionate (TP); the effects of androgen on the expression of implantation-related genes were examined by in situ hybridization. Delayed implantation could be initiated by TP. Dihydrotestosterone was also able to initiate implantation in the delayed-implantation model. The implantation window could be maintained for at least 48 hours by 5 mg TP per mouse. Prostaglandin endoperoxide synthase 2 (Ptgs2) and microsomal prostaglandin E synthase (mPtges) were aberrantly expressed in mouse uterus at implantation sites after delayed implantation was activated by high doses of TP. A low dose of TP led to a delay in embryo implantation, but a high dose caused aberrant expression of both Ptgs2 and mPtges at the implantation site. It is possible that high doses of TP may disturb peri-implantation development or may be involved in early pregnancy loss by disturbing the uterine prostaglandin system.

Effects of testosterone hormone and ages on carcass characteristics of Kacang doe

Forty Kacang doe (average initial BW, 10.2 kg) were used in 4x2 factorial arrangement to determine carcass characteristics. Dose of the testosterone as first factor were assigned to four levels, i.e.: control (T 0 ), 1 dose of testosterone propionate (T 1 ), 2 doses of TP (T 2 ), and 3 doses of TP (T 3 ). The age of animals as the second factor, i.e.: 7-8 months of age (U 1 ) and 9-12 months of age (U 2 ), referred to chevon method. The treatment combinations were replicated 5 times, respectively, so that there were 40 heads of doe. Animals were injected with 0.77 mg of TP/kg BW/d weekly for first dose and the goats were fed for 90 days. The diet were assigned to met or exceed 50 g ADG. The variables included slaughter weight, carcass weight, pelt weight, and Kidney Pelvic Heart (KPH) fat weight. There were significant interaction (P<0.01), except on KPH weight. The best carcass characteristics were significantly resulted from injection of 49 mg TP head -1 week -1 treated on 9 kg of Kacang doe. Key Words : Testosterone, Age, Carcass Characteristic, Kacang Doe