ToxSci Advance Access originally published online on March 28, 2006
Toxicological Sciences 2006 91(2):550-556; doi:10.1093/toxsci/kfj178
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation Exposure Impairs Luteinizing Hormone Signal Transduction and Steroidogenesis in Cultured Human Leydig Cells
* Department of Endocrinology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai-600 113, Tamil Nadu, India; Department of Urology, Madras Medical College and Hospital, Chennai-600 002, Tamil Nadu, India; and Department of Radiation Oncology, Government General Hospital, Chennai-600 014, Tamil Nadu, India
Received August 24, 2005; accepted October 7, 2005
Therapeutic, accidental, and experimental radiation exposures decreased serum testosterone in males, leading to various sexual problems. Since testicular Leydig cells are the predominant source of circulating testosterone, findings on the direct effects of radiation on Leydig cell steroidogenesis and the mechanism behind such effects would be of greater importance to the use of safer radiation doses in cancer therapy and to adopt preventive or therapeutic measures to alleviate postirradiation lesions, respectively. Therefore, this study was undertaken to explore the same using cultured human Leydig cells. Testicles removed from advanced prostatic carcinoma patients were used for isolation and purification of Leydig cells. Purified Leydig cells were cultured and then exposed to different doses (2, 4, 6, 8, and 10 Gy) of fractioned gamma radiation. Normal and irradiated cells were used for luteinizing hormone (LH) receptor quantification or total RNA isolation to study LH receptor mRNA expression or LH/cyclic AMP (cAMP) stimulation test. While LH-stimulated cells were used for cAMP assay, LH- and cAMP-stimulated cells were used for the estimation of steroidogenic enzymes, testosterone and estradiol production. Radiation exposure caused adverse effects on Leydig cell steroidogenesis in a dose-dependent manner. While lower doses (2 and 4 Gy) were ineffective, higher doses (6 Gy and above) drastically decreased LH receptor, basal and LH-stimulated cAMP generation, and basal, LH-, and cAMP-stimulated steroidogenesis. While 2 Gy of radiation exposure increased the LH receptor mRNA level, other doses did not induce any significant change. Therefore, it is concluded that higher doses of radiation impair Leydig cell steroidogenesis by affecting LH signal transduction at the level of both pre- and post-cAMP generation. Decreased level of LH receptors following higher doses of radiation exposure is not coupled with impaired expression of its mRNA.
Key Words: gamma radiation; human Leydig cell; LH signaling; LH receptor expression; steroidogenesis.