Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have evaluated whether the arachidonic acid cascade may be involved in the folding and fusion of the penis and scrotum in masculine differentiation, a possibility raised by recent observations of the involvement of the arachidonic acid cascade in the analogous embryonic processes of elevation and fusion of the palatal shelves and of folding and fusion of the neural tube. To test this hypothesis, during embryonic masculine differentiation in mice of the B10.A strain, we administered certain agents that produce blockade of masculinization. We report that arachidonic acid can reverse the inhibition of masculine development in male embryos produced by estradiol-17 beta or by cyproterone acetate, an androgen receptor-site blocker, and that such reversal can be prevented by an inhibitor of cyclooxygenase, such as indomethacin. We have also found that agents that block the arachidonic acid cascade at the level of phospholipase A2 (cortisone, phenytoin) or at the level of cyclooxygenase (indomethacin, aspirin) also block masculine differentiation and that such antimasculinization is reversed by arachidonic acid. The masculinization of male embryos is inhibited by indomethacin and aspirin, and the masculinization of female embryos produced by exogenous testosterone is prevented by indomethacin. These findings provide evidence that the mechanism by which testosterone organizes the genitalia involves a role of the arachidonic acid cascade leading to prostaglandins at a critical period of development and that interference with testosterone synthesis or action leads to a teratogenic deficiency of arachidonic acid during this time in the genital anlagen.
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PMID:The arachidonic acid cascade is involved in the masculinizing action of testosterone on embryonic external genitalia in mice. 308 81

Testosterone-treated calf thymocytes produce increased amounts of proteins, termed lipokinins, that stimulate phospholipase A2 from snake venom and mammalian tissue. The induction of these proteins by testosterone is blocked by cycloheximide and, thus, requires new protein synthesis. These proteins activate phospholipase A2 stoichiometrically. They are inactivated by boiling, trypsin or alkaline phosphatase but not by deoxyribonuclease or ribonuclease. Lipokinins significantly repair the failure of masculinization in the Tfm mouse with an X-linked deficiency of androgen-receptor. Thus, the post-receptor effects of testosterone on embryonic genitalia may be mediated through stimulation of phospholipase A2 by lipokinins. Moreover, lipokinins may be involved as stimulators of the arachidonic acid cascade, as lipocortins are inhibitors.
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PMID:John Lattimer lecture. Lipokinins: novel phospholipase A2 activators mediate testosterone effects on embryonic genitalia. 318 94

Recently, we identified a protein fraction with phospholipase A2 (PLA2) stimulatory activity (named as PLSP in previous publications) from the fetal male reproductive tract which induced masculine differentiation of the Wolffian duct in vitro. The role of the PLA2-stimulatory activity of this protein was not clear from the past investigations and the present study was designed to elucidate its role. PLSP as expected stimulated snake venom PLA2 and it induced masculinization not only in male explant but also in female explants in a dose-dependent manner in the absence of gonads. However, neither its PLA2-stimulatory activity nor its masculinizing activity was affected after passing it through a PLA2-Sepharose column (a compound expected to eliminate any PLA2 binding component) suggesting that the PLA2-stimulatory activity of PLSP was not at the level of PLA2 enzyme. To investigate whether modulation of the PLA2 substrate by PLSP played a role in producing PLA2-stimulatory activity, we determined the effect of increasing amounts of unlabeled substrate on the PLA2-stimulatory activity induced by PLSP. However, no change in the PLA2-stimulatory activity of PLSP by unlabeled substrate was noticed suggesting against this possibility. The PLA2-stimulatory activity of PLSP, however, was found completely abolished when it was subjected to extensive dialysis, while its protein composition and masculinizing activity remained unaffected. Thus, it appears that PLA2-stimulatory activity of PLSP is associated with a small compound co-purified with masculinizing protein of PLSP and this activity plays no role in inducing masculinization by PLSP.
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PMID:Further characterization of the testosterone inducible protein fraction from the mouse fetal male reproductive tract inducing masculine differentiation in vitro. 849 45