Friday, March 25, 2011

Progesterone's action on sperm finally solved

Two recent articles in Nature reveal a mystery that's been puzzling physiologists for a couple of decades . . . how does progesterone signal sperm cells?

The short version of the story is this . . .

Progesterone is released from the cumulus cells that cling to the outside of the zona pellucida surrounding the ovum. This progesterone binds directly to calcium channels in the sperm's plasma membrane to open.  Influx of calcium ions triggers an increase in flagellum activity.  This increased work is needed for the sperm to get through the zona to the ovum.

Progesterone is a steroid hormone and thus usually enters its target cell and activates transcription of a gene.  In this case, however, progesterone instead directly triggers a calcium channel.  It's not even a second-messenger system, but a direct binding to the channel.

Secretion of progesterone by cumulus cells apparently also provides a chemical gradient that helps sperm navigate toward the ovum.

Recall also that calcium influx into the ovum triggered by contact with a sperm cell plays a role in producing changes within the ovum that result in successful fertilization.

I recommend that my students keep running concept lists on recurring themes or actors in story of human biology.  Here's something they can now add to their calcium list.  Now they can see that a calcium gradient is a truly multipurpose tool in the body.  (For more about running concept lists see

Want to know more?
Sperm mystery solved: Scientists identify the channel by which progesterone activates sperm to swim toward an egg
M. Scudellari
The Scientist Published online 16th March 2011
[Nice summary of the significance of the discovery]

Female hormone could be key to male contraceptive: Progesterone-sensing molecule that guides sperm to egg offers fertility solution.
E. Callaway
NatureNews Published online 16 March 2011 | Nature | doi:10.1038/news.2011.163
[Summary article outlining the papers published in Nature]

Progesterone activates the principal Ca2+ channel of human sperm
Lishko et al.
Nature  471:387–391 17 March 2011 doi:10.1038/nature09767
[Original research findings]

The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm
Strunker et al.
Nature 471:382–386 17 March 2011 doi:10.1038/nature09769
[Original research findings]
From The A&P Professor archive
New discovery about sperm's ability to swim
K. Patton
The A&P Professor published online Feb 18, 2010
[Summary of new discovery that when sperm enter female tract, proton channels in the sperm head open and the resulting pH drop triggers influx of calcium, which gets the flagella started in the first place.  That darn calcium shows up in every part of this story, eh?]

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