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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-12-17
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
255
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Stimulation of tyrosine phosphorylation by progesterone and its 11-OH derivatives: dissection of a Ca(2+)-dependent and a Ca(2+)-independent mechanism.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University of Granada Faculty of Sciences, Campus Universitario "Fuentenueva,", Granada, Spain.
pubmed:publicationType
Journal Article