Ethisterone Research Articles

Comparison of milt and blood parameters including testosterone and gonadotropins levels of sex‐reversed female rainbow trout ( Oncorhynchus mykiss ) by different steroid hormones

All-female progeny is preferable in the reproduction of rainbow trout. Using sex-reversed (SR) female rainbow trout by steroid hormones as broodstock in the reproduction is the most appropriate way to all-female progeny. This study compared mature SR female rainbow trout by ethisterone (ET), 11β-Hydroxyandrostenedione (HD) and 17α-Methyltestosterone (MT) in terms of spermatological parameters and health status, for the first time. Spermatozoa concentration, motility characteristics, seminal plasma pH, testosterone and gonadotropins in seminal plasma and blood serum, blood parameters of SR females were evaluated, comparing with testicular and stripped milt, and blood from normal males (NM). The SR females by HD had greater gonadosomatic index and better motility characteristics compared with other groups. Also, blood parameters of this group were more similar to those in NM. The SR females by ET had the lowest haematocrit and the highest glucose and activities of the enzymes compared with the other groups. The measured hormones were significantly the lowest in both seminal plasma and serum of the ET group. These findings suggested that using of HD for obtaining SR female should be preferred due to having the better quality spermatozoa and health status.

Direct Metal‐Free Preparation of Functionalizable Polylactic Acid‐Ethisterone Conjugates in a One‐Pot Approach

AbstractA series of polylactic acid (PLA) conjugates (PLA‐ES) are synthesized via direct melt polycondensation (DMP) of lactic acid (LA) with ethisterone (ES) in the presence of 0.3 wt% toluenesulfonic acid at 160 °C for 6 h. The drug content of PLA conjugates can be simply adjustable. Further functionalization via Click chemistry is also achieved to extend the biomedicine application of biopolymer based drug delivery.

Molecularly imprinted hollow spheres for the solid phase extraction of estrogens

Solid phase extraction (SPE) is widely used in many different areas, such as environmental, biological, and food analysis, where cleaning and pre-concentration of samples are key steps in the analytical protocol. New materials have significant impact on the development of solid phase extraction. In this paper, mono-dispersed molecularly imprinted hollow spheres (MIHSs) of β-estradiol (E2) were synthesized using silica nanospheres particles as the sacrificial matrix. Compared to the corresponding non-imprinted hollow spheres (NIHSs), the MIHSs with uniform size of 290nm have outstanding affinity in aqueous solution. Static saturation adsorption required only 15min to achieve equilibrium, with a binding capacity (Qmax) of 44.5μmolg−1. The extraction of E2, ethinyl estradiol (EE), diethylstilbestrol (DES), ethisterone (ES) and estrone (E1) from water samples by MIHSs was also investigated. In the spiked samples of tap water, Qinghe river water and Zhanjiang river water, more than 90.42% of E2, but less than 79% of EE, DES, ES and E1 were recovered. The limits of detection (LOD) ranged from 0.1 to 0.26µmolL−1 after solid phase extraction by MIHSs and HPLC–UV analysis. The adsorption capacity of the MIHSs showed no significant deterioration after six rounds of regeneration.

Trace analysis of 28 steroids in surface water, wastewater and sludge samples by rapid resolution liquid chromatography–electrospray ionization tandem mass spectrometry

A sensitive rapid resolution liquid chromatography–tandem mass spectrometry (RRLC–MS/MS) method, combined with solid-phase extraction, ultrasonic extraction and silica gel cartridge cleanup, was developed for 28 steroids including 4 estrogens (estrone (E1), 17β-estradiol (E2), 17α-ethynyl estradiol (EE2), diethylstilbestrol (DES)), 14 androgens (androsta-1,4-diene-3,17-dione (ADD), 17α-trenbolone, 17β-trenbolone, 4-androstene-3,17-dione, 19-nortestoserone, 17β-boldenone, 17α-boldenone, testosterone (T), epi-androsterone (EADR), methyltestosterone (MT), 4-hydroxy-androst-4-ene-17-dione (4-OHA), 5α-dihydrotestosterone (5α-DHT), androsterone (ADR), stanozolol (S)), 5 progestagens (progesterone (P), ethynyl testosterone (ET), 19-norethindrone, norgestrel, medroxyprogesterone (MP)), and 5 glucocorticoids (cortisol, cortisone, prednisone, prednisolone, dexamethasone) in surface water, wastewater and sludge samples. The recoveries of surface water, influents, effluents and sludge samples were 90.6–119.0% (except 5α-DHT was 143%), 44.0–200%, 60.7–123% and 62.6–138%, respectively. The method detection limits for the 28 analytes in surface water, influents, effluents and freeze-dried sludge samples were 0.01–0.24 ng/L, 0.02–1.44 ng/L, 0.01–0.49 ng/L and 0.08–2.06 ng/g, respectively. This method was applied in the determination of the residual steroidal hormones in two surface water of Danshui River, 12 wastewater and 8 sludge samples from two wastewater treatment plants (Meihu and Huiyang WWTPs) in Guangdong (China). Ten analytes were detected in surface water samples with concentrations ranging between 0.4 ng/L (17β-boldenone) and 55.3 ng/L (5α-DHT); twenty analytes in the wastewater samples with concentrations ranging between 0.3 ng/L (P) and 621 ng/L (5α-DHT); and 12 analytes in the sludge samples with concentrations ranging between 1.6 ng/g (E1) and 372 ng/g (EADR).

Hyperferritinemia: An Unexpected Effect of Treatment with Danazol

Hyperferritinemia is most often found in patients as a result of iron overload, infection, inflammation, or malignancy. Danazol, a synthetic derivative of ethinyl testosterone, has not been reported to cause hyperferritinemia. We present three patients observed to have extreme increases in serum ferritin during treatment with danazol.CASES: The first case is a 67 year old male with autoimmune hemolytic anemia, whose ferritin level rose from 983 to 3472 μg/L six months after starting danazol 200mg three times daily. The second is a 79 year old woman with immune thrombocytopenic purpura, whose ferritin was found to be 1109 μg/L after one month on danazol 200mg twice daily (BID) then decreased to188 μg/L one month after discontinuation. The third case had the most dramatic findings. This is a 56 year old female with autoimmune hemolytic anemia characterized by both warm and cold agglutinins with a refractory course. After less than one month on danazol 200 mg BID her ferritin increased from 521 to 2877μg/L. Severe hyperferritinemia persisted until danazol was discontinued. At this time, there was an abrupt fall from 2628 to 191μg/L. In each of these cases, there was no alternative explanation for the changes in ferritin level. In particular, there was no evidence of activation of the acute phase response, nor any indication of hepatotoxicity as reflected in liver enzymes or bilirubin levels. Since observing these cases, we have monitored ferritin levels in 3 other patients being treated in our clinic with danazol, and have seen no change in ferritin level in these 3 patients.DISCUSSION: The effect of danazol in these cases may represent a direct androgenic effect or a non-specific effect. The synthesis of a number of plasma proteins by hepatocytes is known to be influenced by androgen receptor interactions, but this has not been reported to be the case for ferritin; instead it is thought that higher ferritin levels in men are a result of higher iron stores. Nonetheless it is possible that there is a previously unreported influence of androgens on ferritin synthesis, which might be more apparent in patients with moderate iron overload (two of our patients had mildly elevated baseline ferritin levels). An idiosyncratic effect unrelated to androgenic activity seems more likely. (Similarly, there is an inconsistent therapeutic effect of danazol in immune thrombocytopenia and hemolytic anemia and the exact mechanism of action, possibly related to immunosuppression rather than androgen effect, is unknown.) The rapid return of the ferritin level to baseline after discontinuation of danazol shows that the effect is not a result of a change in iron stores. The possibility that danazol (or a metabolite thereof) interferes with the assay of ferritin in serum is made unlikely by our observations in several other danazol-treated patients, in whom no change in ferritin levels were seen. The findings in our cases should be considered when measuring ferritin in patients receiving danazol. Hyperferritinemia in these patients is an unreliable predictor of iron overload. Whether this observation has any implication with respect to the toxicity of danazol is not known.

Effect of Solubilizing 17∝-Ethynyltestosterone in Three Different Solvents on Sex Reversal of Mozambique Tilapia

Abstract This study compares the efficiency of (1) dimethyl sulphoxide (DMSO) + ethanol, (2) ethanol, and (3) acetone + ethanol in solubilizing I7∝-ethynyltestosterone (ET) for treatments in the production of all-male Mozambique tilapias (Oreochroinis mossambicus). Dietary administration of 5 mg ET/kg solubilized in DMSO + ethanol for 11 d, 50 mg ET/kg in ethanol for 11 d, or 50 mg ET/kg in acetone + ethanol for 20 d (to 9-d-old fry) resulted in the production of all-male tilapia populations. The solvent DMSO + ethanol was effective in bringing out the maximum efficiency of ET hormone in the sex reversal of tilapias. The hormone significantly (P < 0.0005) improved growth of the sex-reversed fry. Use of DMSO + ethanol reduced the cost of hormone-treated feed for sex reversal.

Effect of feeding high levels of androgens on the sex ratio of Oreochromis aureus

An experiment in which Oreochromis aureus fry were fed ethynyltestosterone (ET) at levels of 60, 90, 120, and 240 mg/kg of feed for 22 days at 27 to 32°C produced 100% male fish. Feeding methyltestosterone (MT) at levels of 60, 90, and 120 mg/kg of feed produced 96–99% males. Accidental overdosing of O. aureus fry with ET or MT (to the extent of 300% of recommended doses) should not hamper practical-scale production of monosex males.

Effect of danazol on the biochemical abnormality of inherited antithrombin III deficiency.

Seven members of a family affected by hereditary antithrombin III deficiency were identified. The disorder was associated with recurrent spontaneous episodes of phlebitis, deep venous thrombosis, and pulmonary embolism in middle age. Danazol, a 17-alkyl derivative of ethinyl testosterone, which has been used to treat other antiprotease deficiency states, was assessed in the management of two men with antithrombin deficiency. In a dose of 600 mg a day danazol appeared to correct the antithrombin deficiency. This drug may provide a useful adjunct to anticoagulant treatment, particularly before surgery.

Danazol binding and translocation of steroid receptors

Danazol, an isoxazol derivative of ethinyl testosterone which suppresses gonadotropin levels and acts as a weak androgen, is shown by competition studies to bind rat androgen receptor (Ki 10−8M) and progestin receptor (Ki 10−7M) but not estrogen receptor. Effective antigonadotropin doses to the rat in vivo translocate only androgen receptor to target cell nuclei; nuclear receptor levels remain elevated more than 6 hours. The same translocation occurs when rat uteri are incubated with danazol in vitro, showing that the action of danazol is direct and probably does not require metabolic conversion of the drug.

Inducement of sex reversal in Sarotherodon niloticus (Linnaeus)

Two androgens, ethynyltestosterone (ET) and methyltestosterone (MT) and two estrogens, diethylstilbestrol (DES) and estrone (E) were orally administered to gonadally undifferentiated Sarotherodon niloticus fry. Diets with hormones were prepared at the following levels: ET and MT at 30 and 60 mg kg −1 of feed, DES at 25 and 100 mg kg −1 of feed, and E at 100 and 200 mg kg −1 of feed. The fish were fed at 10% body weight per day for 25-, 35- and 59-day periods. All-male populations were produced with ET-60 and MT-60 in all three treatment periods, and with ET-30 and MT-30 during the 35- and 59-day treatments. No estrogen treatment resulted in 100% female populations but only about 10% of the DES-100 treatment populations at the three durations were males. Sex ratios were significantly different ( P < 0.01) from the expected 1:1 ratio in all fish treated with androgens and estrogens. No ovotestis condition was found. Total mortalities in all treatments and controls were uniformly low, ranging from 1.5 to 8.8% for the treatment period.

Danazol in the treatment of Precocious Puberty

Danazol is a synthetic analogue of ethinyl testosterone with a capacity to inhibit gonadotrophin release. Six children (4-10.5 years) have been treated with oral Danazol for up to 17 months. In three females, the precocious puberty is idiopathic, but neurogenic in two other females and one male. Danazol was given in divided doses, 9-17 mg/kg/day, and produced no side effects. In all patients, reduction in breast (testicular) size was noted and further menses were prevented in three patients. Linear growth and bone maturity were not influenced by therapy. Hypothalamo-pituitary maturity was demonstrated prior to treatment by the LH and FSH response to LH/FSH-RH. Reassessment in several children on treatment shows some “blunting” of the peak response to LH/FSH-RH. Improved academic performance was noted in the boy and a useful reduction in sexual drive occurred in the oldest girl. Danazol is effective in controlling some aspects of precocious puberty and further long-term studies are justified.

Danazol-testosterone combination: A potentially effective means for reversible male contraception. A preliminary report

Danazol (an analogue of ethinyl testosterone) was administered to normal adult male volunteers alone or in combination with testosterone propionate or testosterone enanthate to determine the effects on sperm concentration. The drugs were administered for four months. Danazol (600 mg/day) orally (p.o.) produced a modest reduction in sperm counts but danazol (p.o.) plus testosterone propionate 10 mg intramuscularly three times weekly reduced sperm counts to below 2 million/ml in 3 of 4 men. Danazol (600 mg/day, p.o.) plus testosterone enanthate 200 mg intramuscularly once monthly dropped sperm counts to less than 1 million/ml in 3 of 3 men within eight weeks. Androgen withdrawal symptoms were not observed when testosterone was added to the danazol as a combined regimen. It is suggested that danazol plus relatively small doses of testosterone may prove to be an effective and safe male contraceptive.

Evidence of a sex-specific effect of testosterone and progesterone upon L-cystine-aminopeptidase activity in the hypothalamus and paleopallium of the rat.

The activity of L-cystine-aminopeptidase (CAPA) in the hypothalamus and paleopallium of the immature, intact male rat could be stimulated by administration of ethinyl oestradiol and testosterone, whil

Anal fin regeneration in thiouracil‐treated guppies

AbstractMale guppies were kept in a solution of 0.03% thiouracil for 45 days. At this time the gonopodium was cut back and then allowed to regenerate while the fish were maintained in one of the following solutions: (1) thiouracil, (2) aged tap water, (3) 0.01% thyroid powder, (4) 1:500,000 ethynyl testosterone, (5) ethynyl testosterone and thyroid powder, (6) ethynyl testosterone and thiouracil, (7) thyroid powder and thiouracil.Regeneration was greatly inhibited in solutions 1, 2, 5 and 7. Regeneration was normal or almost so in solutions 3, 4 and 6. It is concluded that the thiouracil‐induced inhibition of regeneration of the gonopodium of the guppy is due to the effect of thiouracil on the formation or release of testicular hormones.

Masculinization and tumour-inducing activity of pregneninolone in the female gonads of the viviparous toothcarp Xiphophorus helleri.

Es wird die maskulinisierende und Tumor erzeugende Aktivitat von Pregneninolon beim lebendgebarenden ZahnkarpfenXiphophorus helleri beschrieben.

Studies on the Biological Action of 19-Norsteroids

Various biological activities of 19-Norsteroids, Methyl 19-Nortestosterone (MNT), Ethinyl 19-Nortestosterone (EtNT), Ethyl 19-Nortestosterone (ENT), 19-Nortestosterone (NT) and their esters were investigated. 1) Androgenic activity : According to Eisenberg and Gordan's test, 19-Norsteroids corresponded to 1/1C-1/20 of Testosterone propionate (TP). Ethinyltestosterone (ET) was the weakest (1/40 of TP) and MNT was a little stronger than EtNT. 2) Anabolic activity : By means of Eisenberg and Gordan's test, they corresponded to 1/5-1/20 of TP in anabolic activity, ET was the weakest (1/40 of TP). EtNT was a little weaker than MNT, where as NT was equal to TP, ENT was the strongest among them (1/2, 5 of TP). 3) Estrogenic activity : On Allen-Dolsy test, they corresponded to 1/1,000-1/4,000 of Estradiol (OH2) in estrogenic activity, EtNT was two times stronger than MNT. In uterotrophic activity on Lauson's test, thay had only 1/3,000-1/40,000 of action of OH2. EtNT was the strongest of all. 4) Progestational activity : On Clauberg test by injection they corresponded to 1/2-1/30 of Progesterone (P). MNT and EtNT was 1/30 of P. By oral administration they were distinctly activer than ET, in fact at least two-ten times. Both MNT and ENT were ten times activer than ET. As for the duration of Clauberg's progestational action following a single injection of 20mg. their esters were stronger than free compounds. The effects of both MNT-enanthate (MNTE) and EtNT-enanthate (EtNTE) were recognized even on 10th day after injection. 5) Inhibiting activity on pituitary gonadotrophic potency : Of inhibiting activity on pituitary gonadotrophic potency by testes weight decrease test in rats, EtNT was the strongest of others, MNT and their esters were not so active. By means of gonadotrophic potency test in mice following injection with 19-Norsteroids, EtNT inhibited its action and was the strongest of all. 6) Pregnancy maintenance activity : Activity in Clauberg test and pregnancy maintenance effect in rats were not always pararrel. The 19-Norsteroids were all quite active in even if given by mouth, but pregnancy maintenance effect was rather weak. On Clauberg test 19-Norsteroids were generally stronger when given by mouth than by injection, while in pregnancy maintenance actlvity parenteral application was better than peroral treatment. 7) Effect on sexual cycle of rats : MNT and EtNT inhibited the estrus when given for a long time. In generally the sexual cycle became irregular. 8) Chemical structures and biological activities : There seemed to exist a definite relation between the chemical structures and the biological activities of 19-Norsteroids.

17α-Methyl-19-nortestosteroneおよび17α-Ethynyltestosteroneの数種エステルの合成および黄体ホルモン作用の持続性について

17α-Methyl-19-nortestosteroneおよび17α-Ethynyltestosteroneの数種エステルの合成および黄体ホルモン作用の持続性について

Progestational effectiveness of 19-norethinyl-testosterone by oral route in women.

ConclusionsIt is clear from the foregoing observations that 10 mg nor-ethisterone given twice daily represents a reproducibly effective dose in women for the production of marked progestational changes in the endometrium. The data suggest that very probably one half this dose will not be effective. The comparably effective dose of ethinyl tes-tosterone (ethisterone) would be about 4 times higher(4). Thus the comparative values agree reasonably well in rabbit, monkey, and man(2,3).

The effect of progesterone and anhydrohydroxy-progesterone on nitrogen balance.

The effect of progesterone and anhydrohydroxy-progesterone on nitrogen balance.

The effects of 17-hydroxy-11-dehydrocorticosterone upon the adrenals of normal and of hypophysectomized rats maintained with adrenocorticotropin.

THE authors working with De Majo (1949) showed that methyl testosterone, vinyl testosterone and testosterone propionate in a dosage of 2.5 mg. daily for 20 days and desoxycorticosterone acetate or progesterone at the level of 5 mg. daily for the same period of time produced a significant decrease in the size of the adrenals of normal female rats. No such atrophy was obtained with comparable doses of dehydroisoandrosterone, ethynyl testosterone or ethyl testosterone. It was noted in the course of these studies that testosterone propionate and methyl testosterone caused a decrease, whereas progesterone, desoxycorticosterone acetate and vinyl testosterone produced an increase in the cholesterol concentration of the adrenals. Wells and Kendall (1940) showed that the administration of 1 mg. daily of ll-dehydro-17-hydroxycorticosterone (Cpd. E) to normal rats produced a suppression of growth and a marked decrease in the size of the adrenal glands.