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PubMed1985

Methyltestosterone-induced night blindness.

A 59-year-old man presented with a 3-month history of night blindness and a 9-month history of steatorrhea. Both symptoms had appeared after he had begun taking methyltestosterone. Investigations revealed low serum levels of carotene (0.1 mmol/L) and vitamin A (0.4 to 0.7 mmol/L), anomalous colour perception, elevation of the rod threshold by 3.5 log units in dark adaptometry, and decreased b-wave amplitudes in photopic and scotopic electroretinograms. No biochemical evidence of cholestasis was elicited. The symptoms and the biochemical and electrophysiologic abnormalities resolved within 9 months of the discontinuation of methyltestosterone.

Color Perception↗
PubMed1968

Identification of the fecal metabolites of 17-alpha-methyltestosterone in the dog.

17alpha-Methyltestosterone-4-(14)C was fed to two dogs in an experiment to determine tissue localization and metabolic disposition of this hypocholesterolemic steroid. No accumulation of the drug was found in any tissue, although a small amount of radioactivity was detected in the liver and the ileal mucosa of one animal. Most of the administered radio-activity was excreted in urine and feces. The urinary metabolites consisted largely of highly polar compounds which appeared resistant to glucuronidase treatment or solvolysis procedures. Analysis of the fecal metabolites showed the presence of unchanged methyltestosterone, of four isomeric methylandrostanediols, and of labeled unidentified polar compounds. Of the four identified methylandrostane-diols, the predominating fecal diols were 17alpha-methyl-5alpha-androstane-3beta,17beta-diol (45-62%) and 17alpha-methyl-5-androstane-3alpha,17-diol (12-28%); 17alpha-methyl-5alpha-androstane-3alpha,-17-diol and the 5beta:3beta isomer were found in very small amounts only.

Androstanes↗
PubMed1980

Effects of methyltestosterone on bile secretion in female and male rats.

No adverse effect on bile secretion was noted in methyltestosterone-treated female rats. In male rats, methyltestosterone administration exerted a cholestatic effect, which is not only due to the decrease of bile salt excretion rate, but also to a possible interference of the steroid with bile salt micelle size.

Animals↗
PubMed2001

Cerebrospinal fluid and behavioral changes after methyltestosterone administration: preliminary findings.

BACKGROUND: Anabolic androgen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem. The biological mechanisms underlying behavioral symptom development are poorly understood. SUBJECTS AND METHODS: We examined levels of monoamine metabolites, neurohormones, and neuropeptides in the cerebrospinal fluid (CSF) of 17 healthy men, at baseline and following 6 days of methyltestosterone (MT) administration (3 days of 40 mg/d, then 3 days of 240 mg/d). Subjects received MT or placebo in a fixed sequence, with neither subjects nor raters aware of the order. Potential relationships were examined between CSF measures, CSF MT levels, and behavioral changes measured on a visual analog scale. RESULTS: Following MT administration, levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were significantly lower (mean +/- SD, 103.8 +/- 47 vs 122.0 +/- 50.7 pmol/mL; P<.01), and 5-hydroxyindoleacetic acid (5-HIAA) levels were significantly higher (mean +/- SD, 104.7 +/- 31.3 vs 86.9 +/- 23.6 pmol/mL; P<.01). No significant MT-related changes were observed in CSF levels of corticotropin, norepinephrine, cortisol, arginine vasopressin, prolactin, corticotropin-releasing hormone, beta-endorphin, and somatotropin release-inhibiting factor. Changes in CSF 5-HIAA significantly correlated with increases in "activation" symptoms (energy, sexual arousal, and diminished sleep) (r = 0.55; P =.02). No significant correlation was observed between changes in CSF and plasma MT, CSF MHPG, and behavioral symptoms. CONCLUSIONS: Short-term anabolic androgenic steroid use affects brain neurochemistry, increasing CSF 5-HIAA and decreasing MHPG. Changes in 5-HIAA levels caused by anabolic androgenic steroids are related to the behavioral changes we observed. In this small sample, we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT.

Adolescent↗
PubMed1999

Determination of doping methyltestosterone by capillary electrophoresis immunological analysis with thermally reversible hydrogel and laser-induced fluorescence.

In this paper thermally reversible hydrogel used as a replaceable packed material for capillary electrophoresis was examined. A simple and rapid method of detecting doping methyltestosterone (MTS) was developed, which demonstrated the potential of strong affinity antibodies (k(d) = 10(9)) as a selector for immunologically based separations in serum, not in urine, by capillary electrophoresis. Polyclonal antibodies (Ab) were polymerized on the hydrogel and applied in the separation of fluorescein isothiocyanate (FITC)-labeled antigen and free antigen with laser-induced fluorescence detector (LIF). The results indicated that N-isopropylacrylamide (PNIPA) hydrogel is a steady, replaceable gel. The specific determination of MTS did not require reaching equilibrium of immunological reaction and the PNIPA hydrogel including antibodies can be stockpiled at 4 degrees C, in preparation for determining MTS at any time. It can be used to determine MTS with good precision with a sensitivity lower than 50 ng/mL. The theoretical plate numbers obtained could reach 168,449 for free-antigen. Details of the preparation of hydrogel cross-linked polyclonal antibody and of typical separations of bound and free antigen are presented.

Acrylamides↗
PubMed2000

Corticosteroid biosynthesis in vitro by testes of the grouper (Epinephelus coioides) after 17alpha-methyltestosterone-induced sex inversion.

This study reports the unique compartmentalization of cortisol and 11-deoxycortisol biosynthesis in vitro from [(3)H]17alpha-hydroxyprogesterone (17P) in testicular tissues of groupers after sex inversion induced by 17alpha-methyltestosterone (MT). Before MT implantation, the ovarian tissues produced only nonpolar metabolites. Following sex inversion some 6 months later, synthesis of these nonpolar metabolites was not detectable. Instead, cortisol and 11-deoxycortisol, with yields of about 3% and 14%, respectively, were synthesized together with two other polar metabolites. The corticosteroids and polar metabolites were distinctly nondetectable in ovarian tissues of the control fish throughout the experiment. While the significance of this testicular synthesis of corticosteroids is presently unclear, it could be related to the increased energy demands arising from the reorganization of gonadal tissues during sex inversion.

Animals↗
PubMedDate not supplied

Determination of methyltestosterone using flow injection with chemiluminescence detection.

Methyltestosterone (MT) enhanced the chemiluminescence of potassium permanganate-sodium thiosulphate system in sulphuric acid medium, and this was used as the basis of a novel flow-injection chemiluminescence method for the determination of methyltesterone. Under optimum conditions, the linear response of MT was in the range 3.0 x 10(-8)-8.0 x 10(-6) g/mL, and the detection limit for determination of MT was 1.0 x 10(-8) g/mL. The method was applied to the analysis of fish with recovery in the range 88.0-113.8% with an average RSD of 1.66% (n = 8).

Animals↗
PubMed2006

Methyltestosterone efficiently induces male development in the self-fertilizing hermaphrodite fish, Kryptolebias marmoratus.

A hermaphrodite fish, Kryptolebias marmoratus, is the only known vertebrate that reproduces by self-fertilization. In nature, males have been rarely observed. Low-temperature treatment during late embryonic stages is known to induce males but its efficacy is variable. Here we report that 17alpha-methyltestosterone (MT) treatment of the embryos converted most of the fish to males. We examined a time course of this male induction with histological and marker gene expression analyses. Oogenesis started in the gonads of the control embryo at hatching; spermatogenesis did not start until two months after hatching. In the MT-treated fish, oogenesis started initially as in the control but stopped completely within one month after hatching. Instead, spermatogonial proliferation started earlier than in the control fish and progressed to full spermatogenesis. Expression profiles of the sex-specific marker genes corresponded well with histological observations. From one month after hatching, expression of an oocyte-specific marker, figalpha, and a testicular somatic cell marker, dmrt1, started to increase in the control and in the MT-treated fish, respectively.

Animals↗
PubMed1977

Nature of acid-induced fluorescence of 17alpha-methyltestosterone.

The fluorescence of the 17alpha-methyltestosterone-trichloroacetic acid reaction product, 1,2,10,15,16,17-hexahydro-10,17,17-trimethylcyclopenta[alpha]phenanthren-3-one, in strong acid was investigated. Structural requirements for fluorescence were derived from absorption and fluorescence studies of related phenanthrenones and cinnamylidene compounds possessing a similar chromophore. All compounds showed fluorescence intensity that was structure and pH dependent. Fluorescence is attributed to both enol and protonated species.

Acids↗
PubMed2007

The mRNA expression of P450 aromatase, gonadotropin beta-subunits and FTZ-F1 in the orange-spotted grouper (Epinephelus Coioides) during 17alpha-methyltestosterone-induced precocious sex change.

The orange-spotted grouper Epinephelus coioides is a protogynous hermaphroditic fish, but the physiological basis of its sex change remains largely unknown. In the present study, the 2-year-old orange-spotted grouper was induced to change sex precociously by oral administration of 17alpha-methyltestosterone (MT, 50 mg/Kg diet, twice a day at daily ration of 5% bodyweight) for 60 days. The serum testosterone levels were significantly elevated after MT treatment for 20 and 40 days as compared to control, but the levels of serum estradiol (E(2)) remained unchanged. The expression of P450aromA in the gonad significantly decreased after MT treatment for 20, 40, and 60 days. Accordingly, the enzyme activity of gonadal aromatase was also lower. The expression of FSHbeta subunit in the pituitary was significantly decreased after MT treatment for 20 days, but returned to the control levels after 40 and 60 days; however, the expression of LHbeta subunit was not altered significantly by MT treatment. The expression of FTZ-F1 in the gonad also decreased significantly in response to MT treatment for 40 and 60 days, but its expression in the pituitary was not altered significantly. Interestingly, when tested in vitro on ovarian fragments, MT had no direct effect on the expression of P450aromA and FTZ-F1 as well as the activity of gonadal aromatase, suggesting that the inhibition of gonadal P450aromatase and FTZ-F1 by MT may be mediated at upper levels of the brain-pituitary-gonadal axis. Taken together, these results indicated that FSH, P450aromA, FTZ-F1, and serum testosterone are associated with the MT-induced sex change of the orange-spotted grouper, but the cause-effect relationship between these factors and sex change in this species remains to be characterized.

Animals↗
PubMed1994

Activation of salmon gonadotropin-releasing hormone synthesis by 17 alpha-methyltestosterone administration in yearling masu salmon, Oncorhynchus masou.

Juvenile salmonid pituitary gonadotropin (GTH) contents are elevated after steroid hormone treatment, but the involvement of gonadotropin-releasing hormone (GnRH) is unclear. Activation of salmon GnRH (sGnRH) synthesis by 17 alpha-methyltestosterone (MT) administration has been examined in the brain of yearling masu salmon (future precocious males and immature females) using an in situ hybridization technique combined with radioimmunoassay. Oral MT application markedly increased pituitary GTH II beta, but not GTH I beta, contents in both sexes. In future precocious males, MT treatment increased the number of cells expressing sGnRH mRNA in the preoptic area about threefold, whereas there were no significant differences in the olfactory bulbs and the ventral telencephalon. No significant changes were observed in cell sizes nor the numbers of silver grain per 100 microns2 cell in any of the brain regions. Thus, in future precocious males, preoptic sGnRH neurons may be activated by sex steroids. In contrast, no significant changes were observed in sGnRH mRNA levels of immature females after MT treatment. These differences in responses to sex steroids of sGnRH cells in the preoptic area between future precocious males and immature females suggest that MT has indirect actions via sGnRH and/or direct actions on the pituitary in the former, and that MT acts directly on the pituitary in the latter.

Animals↗
PubMed1995

In vitro metabolism of testosterone by gonads of the grouper (Epinephelus tauvina) before and after sex inversion with 17 alpha-methyltestosterone.

The steroidogenic potential of gonadal tissues of the protogynous grouper (Epinephelus tauvina) was examined before and after sex inversion with 17 alpha-methyltestosterone. Incubations of gonadal tissues of the fish with [3H]testosterone resulted in the biosynthesis of 5 beta-androstane-3 beta, 17 beta-diol and 5 beta-dihydrotestosterone as the only metabolites in the female phase. Although the production of these 5 beta-reduced androgens persisted in the male phase, there was a shift toward the production of 11 beta-hydroxytestosterone and 11-ketotestosterone as major metabolites.

Androstane-3,17-diol↗
PubMed1998

Synthesis of 17,20alpha/beta-dihydroxy-4-pregnen-3-one and 5beta-pregnanes in spermatozoa of primary and 17alpha-methyltestosterone-induced secondary male grouper (Epinephelus coioides).

The in vitro metabolism of [3H]17-hydroxyprogesterone by spermatozoa of primary and 17alpha-methyltestosterone (MT)-induced secondary male grouper (Epinephelus coioides) has been examined. With only the labeled precursor, the four predominant 5beta-pregnanes (17, 20alpha-dihydroxy-5beta-pregnan-3-one; 5beta-pregnan-3alpha,17, 20alpha-triol; 3alpha,17-dihydroxy-5beta-pregnan-20-one; and 17hydroxy-5beta-pregnan-3,20-dione) accounted for 75% of the total product yield, with the remainder comprising 17, 20alpha-dihydroxy-4-pregnen-3-one (17,20alphaP) and traces (3%) of 17,20beta-dihydroxy-4-pregnen-3-one. This is the first report of the synthesis of these 5beta-pregnanes by teleost spermatozoa. The addition of excess unlabeled precursor caused a marked shift to the synthesis of only 17,20alphaP. The steroidogenic profile in spermatozoa of the primary and secondary males appears similar in both cases. The shift to 17,20alphaP synthesis at high substrate concentration may suggest a gonadotropin (GtH) control of 17, 20alphaP synthesis, involving the competition for 17P between the high-activity, low-capacity 5beta-reductases and the low-activity, high-capacity 20alpha-HSD. Poor spermiation in MT-induced males may thus be due to the lack of 17P arising from low GtH secretion in vivo in the secondary males.

17-alpha-Hydroxyprogesterone↗
PubMed1983

Effect of 17 alpha-methyltestosterone, estradiol-17 beta and synthetic LHRH on production of gonadotropic hormone in pituitaries of rainbow trout (organ culture).

Pituitary glands from 6-month-old sexually immature female rainbow trout, Salmo gairdneri, were kept in organ culture for 48 or 72 h. Certain groups of pituitaries were cultivated for 48 h on either control medium or medium with 17 alpha-methyltestosterone (MT), or with estradiol-17 beta (E2) in concentrations of 8.5 X 10(-7) M. Other groups of pituitaries were cultivated for 72 h on control medium, or for 48 h on either control medium or MT-medium or E2-medium, and subsequently for 24 h on medium with synthetic LHRH in concentrations of 8.5 X 10(-7) M and 8.5 X 10(-10) M. Gonadotropic (GTH) cells are identified by Alcian Blue-Periodic Acid Schiff-Orange G staining and the double-antibody immunoenzyme-cytochemical technique using anti-carp beta GTH as the first antibody. A quantitative histological procedure was used to study the nuclear size of the GTH cells in response to the different hormones. Secretory activity was estimated by measuring the gonadotropin (GTH) content in extracts of pituitaries, plasma, and the culture media every 24 h by radioimmunoassay. Cultivation on MT- or E2-enriched medium results in an increase of the total amount of GTH in the pituitary and medium, an accumulation of GTH in GTH-cells (approximately 20 percentage points) and an increase in their nuclear size, indicating a stimulation of GTH synthesis. However, autonomous GTH-release is not affected by these steroids. Subsequent cultivation of the pituitaries for 24 h with LHRH causes stimulation of GTH synthesis (approximately 20 percentage points). Preincubation with steroids increases the GTH synthesis capacity of LHRH only when used in a concentration of 8.5 X 10(-10) M. Moreover, 8.5 X 10(-7) M LHRH causes a stimulation of GTH-release. Preincubation of the pituitaries with steroids increases the responsiveness of GTH-cells to LHRH. It is concluded that GTH-production in pituitaries of immature female rainbow trout can be directly influenced by gonadal steroids and by a hypophysiotropic substance.

Animals↗
PubMed1991

Galanin-like immunoreactivity is increased in the brain of estradiol- and methyltestosterone-treated eels.

A galanin-like peptidergic system was demonstrated in the brain of Anguilla. A group of immunoreactive perikarya was located in the nucleus preopticus periventricularis close to the recessus preopticus. Galaninergic fibers occurred in various brain areas. Galanin identified in mammalian pituitary cells was undetectable in fish adenohypophysial cells. Estradiol increased the immunostaining of the rostral perikarya and brain fibers in both male and female European eels kept in fresh water and in female American eels in sea water. Methyltestosterone, an aromatizable androgen, increased galanin immunoreactivity in rostral perikarya and brain fibers of male European eels and female American eels. The cross-sectional area of these perikarya increased significantly after both treatments whereas cell bodies of the posteroventral hypothalamus were slightly affected. Dihydrotestosterone showed no clear effect. Fibers close to the corticotropes were sometime increased, but galanin synthesis was not induced in pituitary cells. In contrast, estradiol induced galanin synthesis in rat pituitary cells, but had a still controversed effect on hypothalamic galanin. A putative influence of galanin on the pituitary-gonadal axis is discussed as gonadal hormones diversely affect gonadotropes and gonosomatic indices in Anguilla.

Anguilla↗
PubMed1985

The effect of oral medroxyprogesterone acetate and methyltestosterone on sexual functioning in a male contraceptive trial.

Twenty-three men who participated in a 15-month clinical trial to assess the potential effectiveness of using a combination of varying doses of medroxyprogesterone acetate (MPA) and methyltestosterone (MT) as a male contraceptive agent, completed a "sexual problem checklist" every two weeks. The study was divided into three phases: pre-treatment (3 months), treatment (6 months), post-treatment (6 months). The questionnaire evaluated changes in various aspects of sexual behaviour and sexual perception and explored whether the treatment influenced any of the parameters considered. The results indicated a small, but significant, decrease in subjective assessment of sexual drive. This was not, however, accompanied by a change in sexual behaviour, in that subjects experienced the same number of erections, ejaculations and frequency of intercourse. It is concluded that the combination of MPA and MT in the doses used may produce a slight decrease in subjective assessment of sexual drive, but no change in actual sexual behaviour.

Administration, Oral↗
PubMed1985

Effect of 17 alpha-methyltestosterone on the skin and gonads of freshwater male silver eels.

Male silver eels kept in fresh water (FW) were injected with 17 alpha-methyltestosterone (MT). They received 5, 10, 15, or 20 injections (8 micrograms/g every other day) or 6 or 9 injections (4 or 2.5 micrograms/g once a week) and were killed 24 hr after the last injection. Compared to solvent-injected controls, the treated eels appeared darker, the eye diameter was enlarged, the head and the pectoral and caudal fins were black and the melanophore index was maximal. The thickness of the skin (epidermis plus dermis) was significantly increased. Macroscopically, the organs of Syrski (juvenile testes) were slightly larger and less translucent, but the maximal gonosomatic index reached only 1-1.2 in two fishes. Stimulation started in the anterior part of the gonad. Microscopically, all stages of spermatogenesis and spermiogenesis were observed. After 20 injections (high dose, 40 days) or 6 (one case only) and 9 injections (low dose, 57 days), spermatids and spermatozoa were present. These positive results are compared to the negative data previously reported in other countries. The mode of action of the androgen is discussed. It is suggested that it acts for the most part directly on the gonad, but a participation of the pituitary cannot be ruled out, although gonadotrophs appeared only slightly stimulated.

Anguilla↗
PubMed1986

Stimulatory effects of methyltestosterone on pituitary gonadotropic cells and testes leydig cells of the three-spined stickleback, Gasterosteus aculeatus L., in winter.

Male three-spined sticklebacks were kept for a month in short photoperiod at ca. 20 degrees in winter. During this period methyltestosterone (MT), dissolved in the water (35 micrograms/liter), stimulated the appearance of breeding colors and kidney hypertrophy, characters which were both absent in the controls. MT furthermore prevented the onset of spermatogenesis. The gonadotropic cells of the MT-treated fish contained significantly more dilated endoplasmic reticulum and less granules than those of the controls. The nuclei of the testes Leydig cells were enlarged after treatment with MT. These findings suggest the existence of a positive feedback of androgen on the gonadal-pituitary axis of the male stickleback in winter.

Animals↗