Endocrinology, Vol 137, 3999-4009, Copyright © 1996 by Endocrine Society

ARTICLES

The extragenomic action of progesterone on human spermatozoa: evidence for a ubiquitous response that is rapidly down-regulated

RJ Aitken, DW Buckingham and DS Irvine
MRC Reproductive Biology Unit, Edinburgh, Scotland. r.j.aitken@ed- rbu.mrc.ac.uk

Image analysis techniques have been used to demonstrate that progesterone induces a rapid calcium transient in the acrosomal domain of greater than 90% of human spermatozoa (n = 2354). These results are at variance with previous reports, suggesting that progesterone receptors are only expressed on a small subpopulation of these cells, by virtue of their ability to bind fluorescent probes incorporating progesterone 3- (O-carboxymethyl) oxime conjugated to BSA. In the present study, we could confirm that such probes only bound to a small proportion of human spermatozoa (3.01 +/- 0.29%; n = 7557) although 91.79 +/- 1.8% of the same sperm populations exhibited a calcium transient in response to progesterone. These results indicate that the binding of labeled progesterone conjugates to human spermatozoa does not reflect the size of the progesterone responsive population; the response elicited by this steroid is essentially ubiquitous. Progesterone action was shown to involve an influx of extracellular calcium via mechanisms that did not involve voltage sensitive- or second messenger operated-channels, phospholipase C, or G proteins. Despite previous evidence suggesting that progesterone action might involve a GABAA receptor/chloride channel, neither GABA nor the GABA agonist muscimol had any effect on intracellular calcium concentrations in human spermatozoa or influenced their functional competence. The only factor that disrupted the responses of human spermatozoa to progesterone was this steroid itself. Progesterone exposure induced a prolonged period of refractoriness to further stimulation that influenced the capacity of these cells to generate calcium transients, and their ability to exhibit a biological response to changes in intracellular calcium. There are implications in these results for our understanding of the extragenomic action of progesterone on human spermatozoa and the clinical manipulation of this system for the assessment and suppression of human sperm function.

This article has been cited by other articles:

				N. R. Chapman, M. M. Kennelly, K. A. Harper, G. N. Europe-Finner, and S. C. Robson Examining the spatio-temporal expression of mRNA encoding the membrane-bound progesterone receptor-alpha isoform in human cervix and myometrium during pregnancy and labour Mol. Hum. Reprod., January 1, 2006; 12(1): 19 - 24. [Abstract] [Full Text] [PDF]

				C. V. Harper and S. J. Publicover Reassessing the role of progesterone in fertilization--compartmentalized calcium signalling in human spermatozoa? Hum. Reprod., October 1, 2005; 20(10): 2675 - 2680. [Abstract] [Full Text] [PDF]

				P. Morales, M. Kong, E. Pizarro, and C. Pasten Participation of the sperm proteasome in human fertilization Hum. Reprod., May 1, 2003; 18(5): 1010 - 1017. [Abstract] [Full Text] [PDF]

				C. Patrat, C. Serres, and P. Jouannet Progesterone Induces Hyperpolarization after a Transient Depolarization Phase in Human Spermatozoa Biol Reprod, June 1, 2002; 66(6): 1775 - 1780. [Abstract] [Full Text] [PDF]

				J. C. Kirkman-Brown, E. L. Punt, C. L. R. Barratt, and S. J. Publicover Zona Pellucida and Progesterone-Induced Ca2+ Signaling and Acrosome Reaction in Human Spermatozoa J Androl, May 1, 2002; 23(3): 306 - 315. [Full Text] [PDF]

				S. Jagannathan, E. L. Punt, Y. Gu, C. Arnoult, D. Sakkas, C. L. R. Barratt, and S. J. Publicover Identification and Localization of T-type Voltage-operated Calcium Channel Subunits in Human Male Germ Cells. EXPRESSION OF MULTIPLE ISOFORMS J. Biol. Chem., March 1, 2002; 277(10): 8449 - 8456. [Abstract] [Full Text] [PDF]

				F. Francavilla, R. Santucci, B. Macerola, G. Ruvolo, and R. Romano Nitric Oxide Synthase Inhibition in Human Sperm Affects Sperm-Oocyte Fusion but Not Zona Pellucida Binding Biol Reprod, August 1, 2000; 63(2): 425 - 429. [Abstract] [Full Text]

				P. Morales, E. Pizarro, M. Kong, B. Kerr, F. Ceric, and P. Vigil Gonadotropin-Releasing Hormone-Stimulated Sperm Binding to the Human Zona Is Mediated by a Calcium Influx Biol Reprod, August 1, 2000; 63(2): 635 - 642. [Abstract] [Full Text]

				H. Kobori, S. Miyazaki, and Y. Kuwabara Characterization of Intracellular Ca2+ Increase in Response to Progesterone and Cyclic Nucleotides in Mouse Spermatozoa Biol Reprod, July 1, 2000; 63(1): 113 - 120. [Abstract] [Full Text]

				S.J. Publicover and C.L.R. Barratt Voltage-operated Ca2+ channels and the acrosome reaction: which channels are present and what do they do? Hum. Reprod., April 1, 1999; 14(4): 873 - 879. [Abstract] [Full Text] [PDF]

				M. A. Garcia and S. Meizel Progesterone-Mediated Calcium Influx and Acrosome Reaction of Human Spermatozoa: Pharmacological Investigation of T-Type Calcium Channels Biol Reprod, January 1, 1999; 60(1): 102 - 109. [Abstract] [Full Text]

				M. Schaefer, T. Hofmann, G. Schultz, and T. Gudermann A new prostaglandin E receptor mediates calcium influx and acrosome reaction in human spermatozoa PNAS, March 17, 1998; 95(6): 3008 - 3013. [Abstract] [Full Text] [PDF]

				M. Luconi, L. Bonaccorsi, M. Maggi, P. Pecchioli, C. Krausz, G. Forti, and E. Baldi Identification and Characterization of Functional Nongenomic Progesterone Receptors on Human Sperm Membrane J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 877 - 885. [Abstract] [Full Text]

				A. Revelli, M. Massobrio, and J. Tesarik Nongenomic Actions of Steroid Hormones in Reproductive Tissues Endocr. Rev., February 1, 1998; 19(1): 3 - 17. [Abstract] [Full Text]

				R. Aitken, D Harkiss, W Knox, M Paterson, and D. Irvine A novel signal transduction cascade in capacitating human spermatozoa characterised by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation J. Cell Sci., January 3, 1998; 111(5): 645 - 656. [Abstract] [PDF]