Methyltestosterone Research Articles

The effects of gonadal development and sex steroids on growth hormone secretion in the male tilapia hybrid (Oreochromis niloticus � O. aureus)

Profiles of plasma growth hormone (GH) in male tilapia hybrid (Oreochromis niloticus x O. aureus) were measured and compared at different times of the year. The profiles did not appear to be repetitive, however, differences in their nature were observed at the different seasons; the most erratic profiles were seen in the height of the reproductive season (July), while the peaks were more subdued in the spring and disappeared in the autumn. Peaks in male fish were more prominent than in the females when measured in July. Perifused pituitary fragments from fish with a high GSI responded to salmon gonadotropin-releasing hormone (sGnRH) analog (10 nM-1 μM), while those from fish with a low GSI barely responded to even the highest dose. Exposure of perifused pituitary fragments from sexually-regressed fish to carp growth hormone-releasing hormone (cGHRH; 0.1 μM) or sGnRH (I μM) stimulated GH release only after injection of the fish with methyl testosterone (MT; 3 injections of 0.4 mg kg (1)). The same MT pretreatment did not alter the response to dopamine (DA; 1 or 10 μM). GH pituitary content in MT-treated fish was lower than in control fish, which may be explained by the higher circulating GH levels in these fish, but does not account for the increased response to the releasing hormones. Castration abolished the response of cultured pituitary cells to sGnRH (I fM-100 nM) without altering either their basal rate of secretion or circulating GH levels. Addition of steroids to the culture medium (MT or estradiol at 10 nM for 2 days) enabled a GH response to sGnRH stimulation in cells from sexually regressed fish. Pituitary cells which had not been exposed to steroids failed to respond to sGnRH, although their response to forskolin or TPA was similar to that of steroid-exposed cells. It would appear, therefore, that at least one of the effects of the sex steroids on the response to GnRH is exerted proximally to the formation of cAMP, or PKC, presumably at the level of the receptor. An increase in the number of receptors to the GH-releasing hormones, following steroid exposure, would explain also the changing nature of the GH secretory profile in different stages of the reproductive season.

Solid surface room temperature phosphorimetry analysis of yohimbine hydrochloride in pharmaceutical formulations

A new method of analysis for yohimbine hydrochloride pharmaceutical formulations is reported. The phosphorescence characteristics of yohimbine hydrochloride were studied at room temperature employing low background paper substrate. The use of phosphorescence enhancers such as sodium iodide, thallium(I) nitrate, and sodium dodecyl sulfate were optimized to obtain limits of detection at the nanogram level. The interference effects of active ingredients commonly encountered in yohimbine hydrochloride formulations were also evaluated. These included methyl testosterone, strychnine hydrochloride, and tocopherol acetate. The recovery of the method was tested in commercial formulations containing yohimbine hydrochloride and tocopherol acetate. The analyses were performed by both the calibration curve and the standard addition procedure. The recoveries obtained varied from 93.61 ± 3.15% to 101.53 ± 11%. The simplicity, the sensitivity, and the selectivity of the method, associated to the satisfactory recoveries obtained, show the potential of solid surface room temperature phosphorimetry for the analysis of yohimbine hydrochloride formulations.

The effects of recombinant eel growth hormone, methyltestosterone and L-thyroxine on the growth of red sea bream,Pagrosomus major

the effects of recombinant eel growth hormone (reGH), methyltestosterone (MT) and L-thyroxine (T4) on the growth of red sea bream,Pagrosomus major, were investigated. Administration of reGH to fry by immersion at 2 mg/1 for 2 h every 5 days resulted in significant increase in both weight and length, but the condition factor (CF) diminished relative to that of similarly treated controls over the 37 day treatment period. Immersion in 0.1 mg/l T4 also resulted in significant increase in both weight and length and higher survival rate of test fry compared to the controls. Immersion in MT had less effect on growth and high-dose resulted in high mortality. In the second study, injection of 2 μg reGH/(g·wk) caused a significant increase in the specific growth rate (SGR) of test red sea bream fingerlings relative to that of the controls during the 4—week treatment period and maintained the increasing trend over the post-treatment period (weeks 4–6). Injection of MT at a dosage of 1μg/(g·wk) resulted in a significant increase in SGR during the 4—week treatment period. Intramuscular injection of 0.1 μg T4/(g·wk) also resulted in a significant increase in weight. Injection of high-doses of MT and T4 inhibited growth and resulted in darkening skin, bulging eyes and thinning body. In muscle chemical composition, the treated groups had no significant differences compared to the controls, but the high-dose MT and T4 groups showed significant increases in lipid content. Potential practical methods for hormone application in fish culture are discussed.

The effects of total saponins of panax ginseng on hematopoietic progenitor cells in healthy humans and aplastic anemia patients

Ginseng is said to have beneficial effects on anemia. The proliferation effects of total saponins of Panax ginseng (TSPG) on hematopoietic progenitor cell in healthy individuals and 29 patients with aplastic anemia (AA) were observed through bone marrow cultures of burst forming unit-erythroid (BFU-E), colony forming unit-erythroid (CFU-E) and colony forming unit-granulocyte/macrophage (CFU-GM) in vitro compared with methyltestosterone (MT). The results suggest TSPG might prompt the proliferation of normal progenitor cells at a concentration of 20 µg/ml. The numbers of BFU-E,CFU-E and CFU-GM increased by 37.8±2.9%, 31.4±2.9% and 33.3±4.0% respectively overthe controls; furthermore TSPG was still useful to BFU-E, CFU-E growth without Epo in vitro, although the colony numbers were much lower. Otherwise MT was useless to CFU-GM. Of the 29 patients with AA, 14 who responded to MT showed sensitivity to TSPG in marrow culture (the rising rate of colony formation exceeded 30%), but immune-mediated AA (patient’s peripheral blood mononucleated cell suppressed normal hematopoiesis) and stem cell decreased AA (few of colonies were formed) showed almost no expression for TSPG activity because of the immunological suppression system and the absence of progenitors.

The History of Synthetic Testosterone

The era of increasingly sophisticated hormonal treatments led to the synthesis of testosterone in 1935 the primary male hormone produced by the testicles. Since the 1940s countless athletes and bodybuilders have taken testosterone and its primary derivatives to increase muscle mass and to intensify training. In the past 25 years this practice has been maintained by a $1 billion international black market. Scientists are investigating reported short-term side effects of anabolic-androgenic steroids such as increased aggression impaired liver function and reproductive problems. The discovery of testosterone was preceded by a long history of organ use for medicinal purposes based on the principle of similia similibus (treating an organ with itself) dating back to ancient times. Two Austrian researchers (Oskar Zoth and Fritz Pregl) in 1923 were the first to study whether a testicular extract could increase muscle strength and improve athletic performance. Other researchers and experimenters included the Russian chemist Alexander von Poehl (spermine and oxygen transport in 1891) the American Leo L. Stanley (testicle transplantation in 1918) the French-Russian Serge Voronoff (monkey gland transplants during the 1920s) Adolf Butenandt (derived androsterone from urine in 1931) Karoly Gyula David and Ernst Laqueur (isolation of crystalline testosterone in 1935) and Leopold Ruzicka and A. Wettstein (artificial preparation of testosterone in 1935). By 1937 clinical trials in humans employed injections of testosterone propionate as well as oral doses of methyl testosterone. Treatment of women with testosterone has been used for hormone-dependent breast tumors as well as for intensifying the female libido but side effects also appeared (husky voice hair growth). The discovery in the 1940s that testosterone could facilitate the growth of muscle tissue led to its increasing use by West Coast bodybuilders and later by other athletes. An estimated 1 million people take steroids in the US. Clinical uses include hypogonadism growth stimulation in puberty treatment of trauma male fertility regulation and retardation of the aging process.

Murder-suicide under Fluoxetine and Methyltestosterone

Murder-suicide under Fluoxetine and Methyltestosterone

Growth of control and androgen-treated Nile tilapia, Oreochromis niloticus (L.), during treatment, nursery and grow-out phases in tropical fish ponds

. Masculinization of sexually undifferentiated tilapia fry is achieved by oral administration of the androgen 17-α methyltestosterone (MT). An anabolic response to androgen treatment of tilapia has been reported. Growth of control and MT-treated tilapia was evaluated during consecutive treatment, nursery, and grow-out phases under conditions approximating commercial, semi-intensive tilapia farms in Central America. Oreochromis niloticus (L.) fry were fed a 0 or 60 mg/kg MT diet for 28 days. Growth curves for control and MT-treated fish did not have significantly different slopes. Mean harvest fry weights were similar, averaging 0·1 g/fry for both treatments. Fry were subsequently stocked into 0·2-ha nursery ponds for 94 days growth. Slopes of control and MT-treated fish growth curves were not significantly different. Mean final individual weights did not differ significantly between treatments. Control fish did not deviate significantly from the1:1 male: female ratio, but MT-treated fish were 97% males. Control male and MT-treated male fingerlings were stocked for grow-out into 0·1-ha organically fertilized earthen ponds. No significant difference in growth was observed between control and MT-treated fish. Mean gross yields after 150 days and mean final individual weights were similar for both treatments.

Comparison of Conditions for Hormonal Sex Reversal of Mozambique Tilapias

Abstract Roles of selected factors on sex reversal of fry of Mozambique tilapia (Tilapia mossambica) administered 17∝-methyltestosterone (MT) through the diet were investigated. The tested factors were temperature (22–38°C), photoperiod (darkness: light, 0 h:24 h to 24 h:0 h), stocking density (100–2,000 fry/m2), feeding rate (10 or 25% body weight!d), supplementation of the medium with a growth promotor (thyroxine), and storage conditions of MT and MT-treated feed. Survival, growth, and sex-reversing potency of MT were significantly influenced directly or indirectly by temperature, feeding rate, photoperiod, and storage conditions of both MT and MT-treated feed. Stocking density and supplementation of thyroxine in the rearing medium influenced survival and growth. without modifying the sex-reversing potency of MT, when the treated fry were fed ad libitum. Photoperiod and low rearing temperature did not directly alter MT-induced sex reversal but did affect sex reversal indirectly by inhibiting MT-treated ...

Effect of the biological matrix on the urinary testosterone/epitestosterone ratio measured by gas chromatography/mass spectrometry in doping analysis.

Testosterone doping in sport is detected by measurement of an increased testosterone/epitestosterone (T/E) ratio in urine. The critical limit is 6. The present study concerns calibration curves for the T/E ratio measured by gas chromatography/mass spectrometry (electron impact) according to the guidelines of the International Olympic Committee. Testosterone (T) and epitestosterone (E) are measured as trimethylsilyl (TMS)-enol-TMS ethers in selected ion monitoring mode using m/z 432 with methyltestosterone (MT) (m/z 446) as internal standard. Calibration curves corresponding to T/E = 1, 6 and 12 prepared directly, i.e. without extraction of T and E, were non-linear. The non-linearity was caused by an increase of the relative molar response of T with respect to the internal standard MT with increasing concentration level. A mean increase of 82% was observed from T/E = 1 to T/E = 12 (E fixed). Adding T/E corresponding to 1/1, 6/1 and 12/1 to urine without endogeneous hormone content resulted in an almost linear calibration curve along the diagonal, with only a slight increase of the relative molar response of testosterone (16% from T/E = 1 to 12). Apparently, the biological matrix stabilizes the relative molar response over a wide concentration range. At a molar ratio of about 1/1 for T/MT, the relative molar response for direct measurement of T is identical to that observed in the presence of urine matrix, which is explained on the basis of a simple mathematical model. The practical conclusion of this study is that, contrary to the present-day practice, calibration curves for the T/E ratio should be based on T/E added to blank urine taken through the extraction procedure. Otherwise, the T/E ratio of urine sample is systematically easily underestimated by 30% or more.

Androgen-induced prevention of the outgrowth of cranial gonadal suspensory ligaments in fetal rats.

Normal and disturbed testicular descent is frequently approached exclusively through a consideration of the caudal testicular suspensory apparatus. This is surprising, because embryonal gonads develop with both cranial and caudal suspensory ligaments, and the sexes differ with respect to the persistence and development of both the cranial and the caudal ligaments. The current study examined the possible role of fetal testicular androgens in male-specific failure of the development of the cranial gonadal suspensory apparatus in rats. Normal male fetuses were studied, as well as fetuses exposed to the anti-androgen flutamide from day 10 after conception. Females were given daily injections of methyl-testosterone alone or in combination with the anti-androgen cyproterone acetate from day 15 after conception, and were studied on day 22. The cranial ligaments remained of minor extension in normal males but developed considerably in females. They developed in female fashion in males exposed to flutamide, and persisted throughout postnatal life. Cranial ligaments did not develop in females that had been exposed to methyl-testosterone. Simultaneous treatment with a large dose of cyproterone acetate effectively counteracted this effect. Fetal testicular testosterone thus appears to play a key role in the prevention of the outgrowth of the cranial gonadal/genital ligament in rats. The supposed function of this suspensory apparatus makes it likely that its persistence in males, as the consequence of inappropriate androgen action during fetal life, facilitates disturbance of testicular descent. This finding may contribute to understanding developmental disorders underlying disturbed testis descent in humans.

Effect of fluoxymesterone on sex ratio and growth of Nile tilapia, Oreochromis niloticus (L.)

The androgenic and anabolic potential of fluoxymesterone (FM) was evaluated by incorporating the hormone into the feed of Nile tilapia, Oreochromis niloticus(L.) fry. Phenotypic all-male populations were produced when FM was given at 1, 5 and 25mg/kg of feed. Fry fed methyltestosterone (MT) at 60 mg/kg of feed and 0-2 mg of FM per kg of feed had a sex ratio of 97-7% and 87-3% phenotypic males. No positive anabolic effect was evident in response to adding FM or MT to the feed at the end of the 28-day treatment period or after an additional 6 weeks of growth without hormone. Growth was less for fry which received 25 mg/kg of FM compared to those receiving lesser rates of FM, 60 mg/kg MT, and controls.

Effects of induced peripheral anosmia on gonadal maturation in prepubertal male rabbits.

The effect of induced peripheral anosmia on gonadal development and maturation was investigated in sexually immature male rabbits. Furthermore, the effect of agents promoting gonadal maturation (LHRH, hMG or methyl testosterone) on testicular development was examined in anosmic rabbits. Peripheral anosmia was induced by spraying the olfactory mucosa with 5% ZnSO4 solution; its effects were evaluated after a 45-day period, corresponding to the duration of spermatogenesis. Evaluation was based on measurement of body-weight, testicular size, testicular biopsy score count (TBSC) and a standard LHRH test (0 and 30 min) involving measurement of the blood levels of FSH, LH and testosterone before and at the end of the test. Markedly lower final and incremental values were noted in anosmic, compared to intact, animals for body-weight (P less than 0.001), TBSC (P less than 0.001), FSH (P less than 0.01) and LH (P less than 0.05). On the other hand, treatment of the anosmic rabbits with 0.9% saline, resulted in lower FSH, TBSC and testicular size increments than in rabbits treated with LHRH, hMG or testosterone, while testosterone levels and body-weight increments were similar in all groups. These findings indicate that induced peripheral anosmia is probably responsible for the inadequate gonadal maturation in prepubertal anosmic male rabbits. This relationship was confirmed by the observed stimulatory effect of administration of agents activating pituitary gonadotrophin secretion or gonadal function in anosmic animals.

Effect of testosterone on TSH and the development of thyroid tumors in rats induced by N-bis(2-Hydroxypropyl)-nitrosamine.

Effects of testosterone(17α-methyl testosterone) on the serum concentration of TSH(thyroid stimulating hormone) and on the development of thyroid tumors were studied in castrated rats pretreated with N-bis(2-hydroxypropyl) nitrosamine(DHPN). In addition, the dose dependency of testosterone on serum TSH concentration was assessed in castrated animals. The incidences of thyroid tumors induced by DHPN were 69% in non-castrated rats, 40% in castrated rats, 85% in castrated rats treated with 300 ppm testosterone diet, 21% in castrated rats treated with 1500 ppm testosterone diet, 20% and 6% in non-castrated rats treated with 300 ppm or 1500 ppm testosterone diet, respectively. The mean serum TSH concentration in castrated rats treated with DHPN and 1500 ppm testosterone diet showed a tendency of higher than the other group values, but not significantly, and the incidences of thyroid tumors did not demonstrate any clear relation to serum TSH concentration values. The serum TSH concentrations were 2.86±1.86 ng/ml in non-castrated rats and 2.80±0.16, 2.57±0.21, 2.43±0.92, 2.10±0.59, 3.09±1.03, 2.73±0.80 and 3.58±0.16 ng/ml in castrated rats fed on diets containing 0, 100, 300, 600, 900, 1200 and 1500 ppm testosterone, respectively. A dose dependent influence of testosterone on mean seminal vesicle and prostate weights but not on serum TSH concentration as well as thyroid weights was observed. The results, thus, suggest that higher concentration of testosterone without higher concentration of TSH inhibits the development of thyroid tumors in rats treated with DHPN.

Simultaneous determination of yohimbine hydrochloride, strychnine nitrate and methyltestosterone by ion-pair high-performance liquid chromatography

A reversed-phase ion-pair chromatographic method was developed for the simultaneous determination of yohimbine hydrochloride (YOH), strychnine nitrate (SN) and methyltestosterone (MT) in a pharmaceutical preparation (tablet). YOH, SN and MT were extracted and separated within 15 min on an octadecylsilano-silica gel column (15 cm × 4.6 mm I.D., 5 μm particle size). The mobile phase was a mixture of 5 · 10 −3 M sodium octanesulphonate solution (pH 5.5) and methanol (40:60, v/v). The ultraviolet absorption detector was set at 254 nm, and noscapine was used as an internal standard. The recoveries of YOH, SN and MT from a known sample were 101.9 and 101.8 and 99.4%, respectively. By this method, these components in commercial tablets could be simultaneously determined without any interference. The method is sufficiently sensitive, reproducible and accurate.

Effect of Hydrotropic Substances on the Complexation of Sparingly Soluble Drugs with Cyclodextrin Derivatives and the Influence of Cyclodextrin Complexation on the Pharmacokinetics of the Drugs

The influence of hydrotropic compounds on complex formation by 2-hydroxypropyl-/3-cyclodextrin (2-HP-/3-CD) was investigated with methyltestosterone (MeT). Various representatives of the lyotropic series were used for this purpose. Additive hydrotropic effects were observed for nicotinamide and urea, which disrupt the water structure, while structure formers such as sorbitol exerted negative effects. The effects of hydrotropic substances on the phase solubility relationship of MeT showed that inclusion complex formation with 2-HP-/3-CD depends on the degree of ordering of the solvent and is apparently subject to entropy effects. Combined systems comprising 2-HP-/3-CD and auxiliary substances with various underlying solubilizing principles were also investigated. Combination of 2-HP-j8-CD with conventional solubilizers, such as 1,2-propylene glycol or sodium deoxycholate, reduced the solubilization capacity of 2-HP-/3-CD. Competitive displacement of the inclusion molecule from its 2-HP-/3-CD complex by sodium deoxycholate suggested that cholesterol participates in the release mechanism of the inclusion molecule under in vivo conditions. The spontaneous release of complexed drug molecules could indirectly be shown on the basis of the spontaneous action of a complexed dihydropyridine derivative after iv administration in rats. The bioavailability of an investigational drug in cynomolgus monkeys could be enhanced sevenfold by inclusion complexation with 2-HP-/3-CD.

The effect of methyltestosterone on the growth hormone response to the dopamine receptor agonist, apomorphine

1. 1. There is some evidence that androgens affect dopaminergic function in animals and man. We investigated the effect of methyltestosterone (MT) (30 mg po) on the growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine (Apo) HCl (0.5 mg sc), in 9 normal men. MT was given 2 hr before Apo. 2. 2. The peak plasma MT concentration was present 1 hr after administration (19.9±19.5 ng/ml: X ± SD): the concentration at 4 hr was 7.2 ± 4.9 ng/ml. At the time of Apo administration, plasma MT varied from 6.0–24.1 ng/ml. 3. 3. There was no significant effect of MT on Apo-GH secretion (interaction F(7, 56) = 1.08: p = NS). The mean individual peak GH concentration after Apo alone was 20.2 ± 11.9 (X ± SD) vs 22.2 ± 9.9 ng/ml when MT preceded Apo (p = NS). 4. 4. These results suggest that exogenous androgens do not affect DA receptor function in males with normal androgenic function. Lack of effect due to an insufficient dose or duration of administration of MT cannot be excluded.

Methyltestosterone

Methyltestosterone

The effects of methyltestosteone on reproductive function in male greyhounds

Oral administration of methyltestosterone (MT) at 50 mg/dog/day to intact adult male greyhounds for 90 d resulted in decreased (P < 0.05) mean daily sperm output and mean testicular length. Additionally, the mean diameter of seminiferous tubules in MT-treated dogs tended to decrease (P = 0.08). Mean concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and concentrations of testosterone in serum were also decreased or tended to decrease (P = 0.0003 to 0.059) at various sampling periods during MT treatment, suggesting alterations in spermatogenesis resulted from decreased serum concentrations of gonadotropins and steroids. Mean daily sperm output, mean testicular length, mean seminiferous tubule diameter and mean concentrations of FSH in serum were not decreased (P > 0.05) at the end of a 90-d recovery period. However, mean concentrations of serum LH and concentrations of testosterone were still lower (P < 0.05) during five of six and one of six sampling times, respectively, during the recovery period than the pretreatment levels, suggesting a prolonged effect of MT treatment on the pituitary/gonadal axis.

Methyltestosterone

Methyltestosterone

High-density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered

We examined the influence of aromatization of testosterone on serum high-density lipoprotein cholesterol (HDL-C) and postheparin plasma hepatic triglyceride lipase activity (HTLA) in men. Eighteen healthy lean nonsmokers (ages, 20 to 33) were administered androgens in a weekly total dose of 280 mg for 12 weeks in one of three groups: testosterone enanthate (TE) (280 mg/wk intramuscularly [IM]); TE (280 mg/wk IM) + testolactone (TL) (250 mg orally [PO] four times daily); or methyltestosterone (MeT) (20 mg PO twice daily). Serum testosterone achieved steady state levels by 4 weeks with >40 nmol/L (TE and TE + TL) and <15 nmol/L (MeT) while 17b-estradiol (E2) rose to >250 pmol/L (TE) or remained below 70 pmol/L (TE + TL and MeT). LH fell to less than 5 U/L (TE and TE + TL) but remained unchanged with MeT. By 4 weeks, HDL-C had decreased significantly from 1.20 ± 0.13 to 0.77 ± 0.13 mmol/L (MeT), from 1.18 ± 0.15 to 0.89 ± 0.13 mmol/L (TE + TL), and demonstrated no decrease in the TE group across the time course of the study. These changes were preceded by mean increases in HTLA of 102% (MeT) and 55% (TE + TL) over baseline, and no significant change with TE. The changes in HDL-C and HTLA returned to baseline within 2 weeks of steroid cessation. There were no changes in total cholesterol, triglycerides, or insulin in any group but, in the MeT group, apo AI levels decreased and low-density lipoprotein cholesterol (LDL-C) increased. After 12 weeks of treatment, sex hormone binding globulin (SHBG) levels were decreased to 37% (MeT), 54% (TE + TL), and 73% (TE) of baseline levels; these changes were evident by the second week of treatment and returned to baseline by the second week following treatment cessation. These results suggest that TE has little effect on HTLA but when a corresponding increase in E2 levels is prevented, HTLA increases. MeT, which is not metabolized to E2, produced the most dramatic HTLA increases, even at a dose that did not reduce serum LH; thus, hepatic specific properties of 17-alkylated androgens may further increase the atherogenic potential of this class of androgens.