| pubmed-article:10082649 | pubmed:abstractText | Progesterone has previously been shown to exert non-genomic effects on human spermatozoa by opening plasma membrane ion channels and by stimulating protein tyrosine phosphorylation. Here we examined how these two activities are influenced by 11-hydroxyl substitution of the steroid molecule either in the alpha- or in the beta-configuration. Both the 11alpha-OH and the 11beta-OH derivatives of progesterone were more effective than progesterone in stimulating tyrosine phosphorylation, although 11alpha-OH-progesterone was a markedly weaker Ca(2+)-influx inducing agonist than the other two steroids. In Ca(2+)-containing medium, the agonist activity of the 11alpha-OH derivative was weaker than that of the 11beta-OH derivative, and it was completely abolished by genistein, whereas that of progesterone and its 11beta-OH derivative was inhibited only partly by this drug. In contrast, when applied in Ca(2+)-free medium, the 11alpha-OH derivative was the strongest of the three agonists tested, and the effects of all the three steroids were completely abolished by genistein. These data show that the structural motifs of steroid molecules that are responsible for the stimulation of tyrosine phosphorylation are different from those mediating the steroid action on Ca2+ influx through plasma membrane channels. The synthesis of selective agonists of both activities may lead to the development of new pharmacological agents to be used in the treatment of steroid-dependent pathologies. | lld:pubmed |
