Matt Hardy and Benson Akingbemi have been investigating endocrine disruptors and their effects on the reproductive system. They examined the effect of HPTE on testosterone production in developing (progenitor and immature) and adult Leydig cells. The researchers found that the more HPTE that Leydig cells were exposed to, the less testosterone the cells produced. HPTE inhibited testosterone production in developing Leydig cells after ten hours of treatment, and in adult Leydig cells after 18 hours. Inhibition of Leydig cells was due to the down regulation of one of four enzymes that catalyze the reactions that occur during androgen biosynthesis.
To determine the reversibility of HPTE-induced testosterone inhibition, the researchers waited 18 hours in each case to see whether testosterone production in these cells recovered to the levels observed in control cells. When treated for three hours, testosterone production by immature and adult Leydig cells rebounded within the 18-hour recovery period, but remained significantly inhibited within progenitor Leydig cells. When treatment lasted six or more hours, however, immature and adult Leydig cells also failed to fully resume testosterone production within the 18-hour recovery period. The onset of HPTE action and the reversibility of its effect showed that Leydig cells are more sensitive to this compound during pubertal differentiation than in adulthood.
Hardy, a reproductive biologist at the Population Council's Center for Biomedical Research, comments that "While HPTE and similar agents are of concern for environmental reasons, studying them may also help us identify new molecular targets for male contraceptives." The Center is one of the world's leading laboratories for contraceptive development and for investigation of the male reproductive system. Hardy and colleagues plan to study the effects of other endocrine disruptors on Leydig cells.
* "A Metabolite of Methoxychlor, 2,2-Bis(p-Hydroxyphenyl)-1,1,1-Trichloroethane, Reduces Testosterone Biosynthesis in Rat Leydig Cells Through Suppression of Steady-State Messenger Ribonucleic Acid Levels of the Cholesterol Side-Chain Cleavage Enzyme"
Benson T. Akingbemi, Center for Biomedical Research, Population Council; Ren-Shan Ge, Center for Biomedical Research, Population Council; Gary R. Klinefelter, Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC; Glen L. Gunsalus, Center for Biomedical Research, Population Council; and Matthew P. Hardy, Center for Biomedical Research, Population Council.
To view an abstract of the research article go to: http://intl.biolreprod.org/cgi/content/abstract/62/3/571
To view a report about the research go to: http://www.popcouncil.org/publications/popbriefs/pb5(4)_3.html
To view a summary of the research undertaken in the laboratory of Matthew Hardy go to: http://www.popcouncil.org/biomed/mhardy.html
The Population Council is an international, nonprofit, nongovernmental institution that seeks to improve the wellbeing and reproductive health of current and future generations around the world and to help achieve a humane, equitable, and sustainable balance between people and resources. The Council conducts biomedical, social science, and public health research and helps build research capacities in developing countries. Established in 1952, the Council is governed by an international board of trustees. Its New York headquarters supports a global network of regional and country offices.
Journal
Biology of Reproduction