"The first and rate-limiting enzyme in the polyamine biosynthesis pathway is ornithine decarboxylase (ODC). ODC is tightly regulated, and one of the most rapidly degraded mammalian proteins, and its degradation is regulated by polyamines in a ubiquitin independent manner.
The polyamines spermine, spermidine and their precursor putrescine are ubiquitous organic polycations that play an important role in regulating fundamental cellular processes, most notably the process of cell growth and proliferation. Depletion of cellular polyamines results in growth cessation, while increased intracellular polyamine levels are associated with cancer. Therefore, polyamines concentration must be maintained within a narrow optimal range. This is achieved by regulation at multiple control levels that include synthesis, uptake, excretion and inter-conversion.
ODC activity is induced during growth stimulation of quiescent cells. and is constitutively increased in cells transformed by oncogenes, treated with carcinogens, infected by viruses, and in a variety of malignancies."
Principal Investigator, Weizmann Institute of Science
Putrescine Water - Fountain of Youth for Eggs?
Ottawa scientist has discovered a critical reason why women experience fertility problems as they get older. Putrescine could reduce the rate at which middle-aged women produce eggs with the incorrect number of chromosomes, the leading cause of reduced fertility and increases in miscarriages and congenital birth defects
The breakthrough by Dr. Johné Liu, a senior scientist at the Ottawa Hospital Research Institute and professor at the University of Ottawa, also points to a simple solution that could increase the viability of egg cells for women in their late 30s and older putrescine water.
In an online editorial published by Aging based on
his recently published findings, Liu outlines how
a simple program of drinking water or taking a pill
that contains the naturally occurring compound
putrescine could reduce the rate at which
middle-aged women produce eggs with the incorrect
number of chromosomes, the leading cause of reduced
fertility and increases in miscarriages
and congenital birth defects.
Putrescine is naturally produced in mammals by
an enzyme called ornithine decarboxylase,or ODC,
and is easily absorbed and cleared by the body.
In female mammals, ODC levels rise during ovulation,
when the egg cell matures and is released from the ovary.
Dr. Liu has shown that ODC levels rise very little
in older females. He has also shown that inhibiting ODC
levels in young mice leads to an increase in egg cells
with chromosomal defects.
Taking this a step further, Dr. Liu's team gave older mice putrescine water in the period immediately leading up to and during ovulation, and found that it reduced the incidence of defective eggs by more than 50%.
This is a remarkable outcome for such a simple approach," says Dr. Liu. "However, we could not have imagined this without first understanding the role that ODC and putrescine play in maintaining the chromosomal integrity of egg cells. While there is work to be done before it can be approved for clinical use, we feel this approach could be used for natural conception as well as in vitro fertilization."
Although promising, a putrescine pill is still a long
way from being available on the market.
Putrescine is toxic to the fetus if administered after
conception, which makes timing, dosage and
Accordingly, this approach must go through the
appropriate stages of testing to determine
its clinical safety and effectiveness in humans.
The full paper, "Deficiency of ovarian ornithine decarboxylase contributes to aging-related egg aneuploidy in mice," was recently accepted for publication online ahead of print by Aging Cell. The editorial was published online by Aging on November 23, 2012. Yong Tao, of the Ottawa Hospital Research Institute and the University of Ottawa, is co-author on both publications.
Funding for this research was provided by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada and a partial scholarship from the Canadian Institutes of Health Research's Training Program in Reproduction, Early Development, and the Impact on Health.
About the Ottawa Hospital Research Institute (OHRI)
The Ottawa Hospital Research Institute (OHRI) is the research arm of The Ottawa Hospital and is an affiliated institute of the University of Ottawa, closely associated with the university's Faculties of Medicine and Health Sciences. OHRI includes more than 1,700 scientists, clinical investigators, graduate students, postdoctoral fellows and staff conducting research to improve the understanding, prevention, diagnosis and treatment of human disease. Research at OHRI is supported by The Ottawa Hospital Foundation. www.ohri.ca
About the University of Ottawa
The University of Ottawa is committed to research excellence and encourages an interdisciplinary approach to knowledge creation, which attracts the best academic talent from across Canada and around the world. It is an important stakeholder in the National Capital Region's economic development.
Original article: http://www.ohri.ca/newsroom/newsstory.asp?ID=326