Molecular Human Reproduction, Vol. 8, No. 4, 326-332,
April 2002
© 2002 European Society of Human Reproduction and Embryology
Testis and spermatogenesis |
Inhibitors of receptor tyrosine kinases do not suppress progesterone-induced [Ca2+]i signalling in human spermatozoa
1 School of Biosciences, University of Birmingham, 2 Faculty of Medicine, McGill University, Montréal, Québec, Canada, 3 Reproductive Biology and Genetics Research Group and 4 Department of Medicine, The Medical School, University of Birmingham, B15 2TT and 5 Assisted Conception Unit, Birmingham Women's Hospital, Birmingham B15 2TG, UK
Previous studies have implicated receptor tyrosine kinases in progesterone-induced [Ca2+]i signalling, and consequent induction of the acrosome reaction, in human spermatozoa. We have investigated the effects of tyrosine kinase inhibition on [Ca2+]i responses in large numbers of individual human spermatozoa. Genistein (5, 50 and 250 µmol/l), an inhibitor of receptor-linked tyrosine kinases, significantly inhibited the progesterone-induced acrosome reaction (P < 0.05). However, we could detect no effect of genistein on progesterone-induced [Ca2+]i signalling. In control experiments, application of progesterone induced a significant transient [Ca2+]i response in ~77% of cells and a sustained [Ca2+]i ramp/plateau in ~48% of cells (n = 26; 5411 cells). In preparations pretreated with genistein (50 µmol/l), significant transient and sustained responses were detected in 69.5 and 39.1% of cells respectively (n = 5; 1109 cells). The amplitudes of both transient and sustained [Ca2+]i responses were similar in control and genistein-pretreated preparations. Tyrphostin A47 (100 µmol/l), another receptor tyrosine kinase inhibitor, also failed to inhibit either the transient or sustained [Ca2+]i response (n = 3; 468 cells). Assessment of tyrosine phosphorylation of two sperm proteins (p105/81) showed greatly increased levels of phosphotyrosine in response to capacitation but a negligible increase in response to progesterone stimulation. Pretreatment with genistein (50 and 250 µmol/l) decreased capacitation-induced tyrosine phosphorylation and resulted in a loss of phosphorylation in response to progesterone treatment. We conclude that neither the transient nor sustained phases of the progesterone-induced [Ca2+]i response require receptor tyrosine kinase signalling. Previous reports of modulation of the progesterone-induced [Ca2+]i signal by tyrosine kinase inhibition probably reflect inhibition of the acrosome reaction.
Ca2+/genistein/human spermatozoa/progesterone/tyrosine kinase
6 To whom correspondence should be addressed at: School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK. E-mail: j.kirkmanbrown{at}bham.ac.uk
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