title: Differential concentration and time dependent effects of progesterone on kinase activity, hyperactivation and acrosome reaction in human spermatozoa.
abstract: Progesterone has been identified to be one of the physiological regulators of sperm hyperactivation and acrosome reaction. However, the high sensitivity of human spermatozoa to progesterone implies that many may undergo premature hyperactivation and acrosome reaction thereby compromising their ability to fertilize. We hypothesized that if a spermatozoon has to preclude the occurrence of these events prematurely, there should be differential dose- and time-dependent effects on motility and acrosome reaction. We observed that low concentrations of progesterone (10 and 100 nm) induce sperm motility and activate tyrosine kinase; higher concentrations (1-10 μm) are required to induce extracellular signal regulated kinases 1/2 (Erk1/2), p90 ribosomal S6 kinase (p90RSK), p38 mitogen-activated protein kinase (p38MAPK), c-Jun N-terminal kinase (JNK1) and AKT phosphorylation, hyperactivation and acrosome reaction. The induction of acrosome reaction and tyrosine phosphorylation in response to higher concentration of progesterone is not absolutely dependent on activation of T-type voltage-gated Ca(2+) channel or CatSper as Mibefradil did not completely abrogate progesterone-mediated effects. These results imply that although the spermatozoa are sensitive to low concentrations of progesterone, they only activate motility and tyrosine kinase activation; higher concentrations are required to induce hyperactivation and acrosome reaction probably by activating multiple kinase pathways including the MAPK and AKT.
authors: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Mumbai, India.
authors: V
authors: V
authors: Sagare-Patil
authors: M
authors: M
authors: Galvankar
authors: M
authors: M
authors: Satiya
authors: B
authors: B
authors: Bhandari
authors: S K
authors: SK
authors: Gupta
authors: D
authors: D
authors: Modi
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects*; D020747:Calcium Channels, T-Type / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D010766:Phosphorylation; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000187:drug effects / Q000378:metabolism; D013075:Sperm Capacitation / Q000187:drug effects*; D013081:Sperm Motility / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020747:Calcium Channels, T-Type; D020748:Mibefradil; D011374:Progesterone; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases