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Progesterone induces acrosome reaction in stallion spermatozoa via a protein tyrosine kinase dependent pathway.
Abstract: Progesterone (P(4)) is a physiological inducer of the acrosome reaction (AR) in stallion spermatozoa. However, the capacitation-dependent changes that enable progesterone binding, and the nature of the signaling cascade that is triggered by progesterone and results in induction of the AR, are poorly understood. The aim of the current study was, therefore, to investigate the protein kinase dependent signaling cascades involved in progesterone-mediated induction of the AR in stallion spermatozoa. In addition, we aimed to determine whether bicarbonate, an inducer of sperm capacitation, acted via the same pathway as P(4) or whether it otherwise synergized P(4)-mediated induction of the AR. We examined the effect on AR progression of specific inhibitors and stimulators of protein kinase A (PKA), protein kinase C (PKC), protein kinase G (PKG), and protein tyrosine kinase (PTK), in the presence or absence of 15 mM bicarbonate and/or 1 microg/ml progesterone. Progression of the AR was assessed using the Pisum sativum agglutinin conjugated to fluorescein iso thiocyanate (PSA-FITC) staining technique. Bicarbonate specifically activated a PKA-dependent signaling pathway, whereas the effect of P(4) was independent of PKA. Conversely, while P(4)-mediated AR induction was dependent on PTK, the effects of bicarbonate were PTK-independent. Finally, although the AR inducing effects of both P(4) and bicarbonate were sensitive to staurosporin, a potent blocker of PKC activity at moderate (50 nM) concentrations, the effect of P(4) was completely blocked at 50 nM staurosporin, whereas that of bicarbonate was only completely inhibited by much higher concentrations (2 microM) where staurosporin also inhibits PKA activity. In conclusion, P(4)-mediated activation of the AR is dependent on a pathway that includes both PTK and PKC. While the effects of bicarbonate on the AR are mediated via a separate PKA-dependent signaling pathway, P(4) and bicarbonate have synergistic effects on the AR.
Copyright 2003 Wiley-Liss, Inc.
Publication Date: 2002-11-07 PubMed ID: 12420307DOI: 10.1002/mrd.10216Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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This research investigates how progesterone, a hormone, triggers a process known as the acrosome reaction (AR) in stallion spermatozoa. The researchers aimed to understand the biochemical process behind this, particularly the involvement of protein kinases, and also the role of bicarbonate.
Acrosome Reaction
- The acrosome reaction (AR) is a critical stage in the fertilization process in which the sperm cell releases enzymes to penetrate the egg.
- Progesterone, a hormone released by the female reproductive system, is known to induce the AR in the spermatozoa of stallions, but the exact mechanism behind this is not clearly understood.
Aims of the Study
- The study aimed to explore the the role of protein kinases in the signaling process that leads to AR upon exposure to progesterone (P4).
- The researchers also wanted to understand how bicarbonate, another compound known to induce sperm capacitation, interacted with these pathways.
Methods
- Protein Kinase A (PKA), Protein Kinase C (PKC), Protein Kinase G (PKG), and Protein Tyrosine Kinase (PTK) were investigated using specific inhibitors and stimulators.
- The AR progression was studied under different conditions: introduction of bicarbonate, progesterone, or their combination.
- The effect was measured using a staining technique involving the Pisum sativum agglutinin conjugated to fluorescein iso-thiocyanate (PSA-FITC).
Findings
- Bicarbonate triggered a specific PKA-dependent signaling pathway, whereas P4’s effect was independent of PKA.
- Conversely, the induction of the AR by P4 was dependent on PTK. But bicarbonate’s effects were PTK-independent.
- Both P4 and bicarbonate’s AR-inducing effects were sensitive to staurosporin, a PKC blocker, but the sensitivity differ: P4’s effect was completely blocked at moderate concentrations, while bicarbonate required significantly higher concentrations for complete inhibition.
Conclusion
- P4 activates the AR through a pathway involving PTK and PKC.
- Bicarbonate affects the AR via a different PKA-dependent signaling pathway.
- However, P4 and bicarbonate have a synergistic effect on the AR, indicating these two substances work together to enhance the process.
Cite This Article
APA
Rathi R, Colenbrander B, Stout TA, Bevers MM, Gadella BM.
(2002).
Progesterone induces acrosome reaction in stallion spermatozoa via a protein tyrosine kinase dependent pathway.
Mol Reprod Dev, 64(1), 120-128.
https://doi.org/10.1002/mrd.10216 Publication
Researcher Affiliations
- Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
MeSH Terms
- Acrosome Reaction / drug effects
- Acrosome Reaction / physiology
- Animals
- Bicarbonates / metabolism
- Cyclic AMP / metabolism
- Enzyme Activators / metabolism
- Horses
- Male
- Progesterone / metabolism
- Progesterone / pharmacology
- Protein Kinase C / metabolism
- Protein-Tyrosine Kinases / antagonists & inhibitors
- Protein-Tyrosine Kinases / metabolism
- Signal Transduction / physiology
- Spermatozoa / metabolism
Citations
This article has been cited 4 times.- Denisenko V, Chistyakova I, Volkova N, Volkova L, Iolchiev B, Kuzmina T. The Modulation of Functional Status of Bovine Spermatozoa by Progesterone. Animals (Basel) 2021 Jun 15;11(6).
- Ryu DY, Kim YJ, Lee JS, Rahman MS, Kwon WS, Yoon SJ, Pang MG. Capacitation and acrosome reaction differences of bovine, mouse and porcine spermatozoa in responsiveness to estrogenic compounds. J Anim Sci Technol 2014;56:26.
- Fayrer-Hosken R, Stanley A, Hill N, Heusner G, Christian M, De La Fuente R, Baumann C, Jones L. Effect of feeding fescue seed containing ergot alkaloid toxins on stallion spermatogenesis and sperm cells. Reprod Domest Anim 2012 Dec;47(6):1017-26.
- McPartlin LA, Visconti PE, Bedford-Guaus SJ. Guanine-nucleotide exchange factors (RAPGEF3/RAPGEF4) induce sperm membrane depolarization and acrosomal exocytosis in capacitated stallion sperm. Biol Reprod 2011 Jul;85(1):179-88.
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