25 Mar Steroid Signal That Makes Sperm React Quickly Identified
MedicalResearch.com Interview with:
Melissa Miller, PhD
Postdoctoral fellow at both UC Berkeley and UC San Francisco
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Miller: This work builds on years of observed, but unexplained, phenomena within sperm cells which respond almost instantaneously to the presence of the steroid hormone progesterone. Typically, steroid signaling occurs through a long, slow process that involves the modification of gene amount within a cell. However, there is an alternative mechanism that is not well understood that works differently and is termed non-genomic progesterone signaling. We found that progesterone in human sperm cells binds to a protein called ABHD2 and activates its activity to clear the cell of the endogenous cannabinoid 2AG. 2AG is an inhibitor of sperm activation and its removal from the cellular membrane allows the sperm cells to change its motility so that it may reach and fertilize the egg. Men who’s sperm is unable to undergo this progesterone activated motility change are infertile.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Miller: Clinicians and patients should be aware that this research is at the basic science level. This means, even though the results from this study are extremely exciting and point to a new target for unisex contraception design and possibly a new biomarker for male infertility, the clinical impact of this finding is still a few years from realization.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Miller: Sperm are only one cell type that maintain expression of this protein. It is highly likely that non-genomic progesterone signaling in other cells, such as neurons and vascular smooth muscle cells is also regulated by ABHD2 or similar proteins. We would like to investigate the role of this non-genomic steroid signaling in other cell types to determine whether the action of progesterone on ABHD2 is unique to sperm cells.
MedicalResearch.com: Is there anything else you would like to add?
Dr. Miller: This work highlights an area of research that has been overlooked for many years, mainly the understanding basic human sperm physiology. With the paucity of research that exists on the subject it is no surprise that 80% of infertile men have no clear cause for their infertility. To add fuel to the fire, the prevalence of infertility in men is similar or even slightly higher than for other more well-studied diseases such as diabetes for example. Male infertility affects about 11% of the reproductive-age population while diabetes (both type I and type II) affects approximately 9%. We hope our research and the research of our colleagues inspires more people to delve in to the field of reproductive biology and in particular towards a better understanding of the effect of the male partner on fecundity.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Citation:
R. Miller, N. Mannowetz, A. T. Iavarone, R. Safavi, E. O. Gracheva, J. F. Smith, R. Z. Hill, D. M. Bautista, Y. Kirichok, P. V. Lishko. Unconventional endocannabinoid signaling governs sperm activation via sex hormone progesterone.
Science, 2016; DOI: 10.1126/science.aad6887
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Dr. Melissa Miller (2016). Steroid Signal That Makes Sperm React Quickly Identified MedicalResearch.com
Last Updated on March 25, 2016 by Marie Benz MD FAAD