Application of α- and ß-naphthoflavones as monooxygenase inhibitors of Absidia coerulea KCh 93, Syncephalastrum racemosum KCh 105 and Chaetomium sp. KCh 6651 in transformation of 17α-methyltestosterone.

In this work, 17α-methyltestosterone was effectively hydroxylated by Absidia coerulea KCh 93, Syncephalastrum racemosum KCh 105 and Chaetomium sp. KCh 6651. A. coerulea KCh 93 afforded 6ß-, 12ß-, 7α-, 11α-, 15α-hydroxy derivatives with 44%, 29%, 6%, 5% and 9% yields, respectively. S. racemosum KCh 105 afforded 7α-, 15α- and 11α-hydroxy derivatives with yields of 45%, 19% and 17%, respectively. Chaetomium sp. KCh 6651 afforded 15α-, 11α-, 7α-, 6ß-, 9α-, 14α-hydroxy and 6ß,14α-dihydroxy derivatives with yields of 31%, 20%, 16%, 7%, 5%, 7% and 4%, respectively. 14α-Hydroxy and 6ß,14α-dihydroxy derivatives were determined as new compounds. Effect of various sources of nitrogen and carbon in the media on biotransformations were tested, however did not affect the degree of substrate conversion or the composition of the products formed. The addition of α- or ß-naphthoflavones inhibited 17α-methyltestosterone hydroxylation but did not change the percentage composition of the resulting products.

Vitamin C Modulates the Immunotoxic Effect of 17α-Methyltestosterone in Nile Tilapia.

The synthetic androgen 17α-methyltestosterone (MT) is profusely used and practically needed in the production of all-male Nile tilapia fry; however, such androgenic hormones badly disrupt the immune system. This study aimed to alleviate or counteract the immunotoxic effect of MT using vitamin C (ascorbic acid or vit C). Our results show that the highest phagocytic activity (PA), phagocytic index (PI), and lysozyme activity were detected in the vit C group and the MT plus vit C group. Furthermore, PA and PI were significantly suppressed, but lysozyme activity was stronger in the MT group than in the control. No differences were detected in the differential leukocyte count among the studied groups. Moreover, vit C obviously reduced the upregulated expression level of the innate immune-related genes, interleukin 1ß (il1ß), interleukin 8 (il8), tumor necrosis factor α (tnfα), CC-chemokine, Toll-like receptor 7 (tlr7), immunoglobulin M (IgM) heavy chain, and cellular apoptosis susceptibility (cas) induced by MT, excluding tnfα in the liver and CC-chemokine and tlr7 in the kidney. The micronucleus frequency was found to significantly improve in the vit C plus MT group in comparison to that in the MT group. Normal histoarchitecture of the liver, kidney, and spleen was observed in all the groups, except for the frequently observed melanomacrophage centers in the spleen and kidney of the fish that were treated with vit C and vit C plus MT. More importantly, our findings demonstrate that the upregulation of immune-related genes is not necessarily a sign of a stimulated or enhanced immune system.

Chronic administration of anabolic steroids disrupts pubertal onset and estrous cyclicity in rats.

Use of anabolic-androgenic steroids (AASs) is becoming increasingly popular among adolescent girls, yet the effects of AASs on female physiology and development are not well understood. The present study compared the effects of chronic exposure to three individual AASs, stanozolol (0.05-5 mg/kg), 17alpha-methyltestosterone (0.5-5 mg/kg), and methandrostenolone (0.5-5 mg/kg) on the onset of puberty and estrous cyclicity in the rat. Female rats received daily injections of AASs for 30 days (Postnatal Day [PN] 21-51). Rats receiving the highest dose of each of the AASs (5 mg/kg) displayed vaginal opening at a younger age than rats receiving the oil vehicle. The day of first vaginal estrus was delayed in rats receiving stanozolol (5 mg/kg) or 17alpha-methyltestosterone (0.5-5 mg/kg) but not in rats receiving methandrostenolone. At the highest dose (5 mg/kg), each of the AASs reduced the incidence of regular estrous cyclicity during the treatment period. Concurrent administration (on PN21-51) of the androgen receptor antagonist, flutamide (10 mg/kg, twice daily), reversed the effects of 17alpha-methyltestosterone (5 mg/kg) on vaginal opening. Flutamide administration also eliminated the effects of stanozolol (5 mg/kg) and 17alpha-methyltestosterone (5 mg/kg) on the day of first vaginal estrus. In contrast, rats receiving flutamide and methandrostenolone (5 mg/kg) exhibited first vaginal estrus earlier than controls. The present results indicate that chronic exposure to AASs during development has deleterious effects on the female neuroendocrine axis and that these effects appear be mediated via multiple mechanisms.

Resistance of androgen-mediated aggressive behavior in mice to flutamide, an antiandrogen.

Flutamide (FTA), an anti-androgenic compound, inhibited the effects of methyltestosterone (MT) on the weight of the ventral prostate, seminal vesicles and levator ani in male castrate mice. Castration prevented the development of aggressive behavior in mice isolated for 3 weeks. While chronic administration of MT to castrate isolated mice returned the incidence of fighting behavior to control values, chronic administration of FTA + MTdid not significantly reduce the incidence of fighting as compared to castrate + MT values. These results suggest that the mechanism for androgen stimulation of secondary sex organ weight may differ from that involved in the development and maintenance of aggression resulting from isolation.