Epididymal Phenotype in Luteinizing Hormone Receptor Knockout Animals and Its Response to Testosterone Replacement Therapy1

Previous studies reported that epididymis contains functional LH receptors. The LH receptor knockout mice, which have ep-ididymal phenotypes, gave us an opportunity to test the hypoth-esis that testosterone replacement alone may not be sufficient to reverse phenotypes to wild-type epididymis. The morpholog-ical phenotype in knockout animals includes a decrease in lu-minal diameter of the proximal and distal caput and cauda ep-ididymis, the absence of clear and halo cells in the epithelial lining, a decrease in the height of principal cells and the number of cells containing cilia, a decrease in cilia length, and a change from basal to central location of nuclei in the principal cells. The biochemical phenotype includes a decrease in periodic acid-Schiff reaction product, reflecting the glycogen and gly-coprotein synthesis and secretion, a decrease in androgen re-ceptor (AR) and estrogen receptor (ER)b, and an increase in ERa levels. Twenty-one-day testosterone replacement therapy in 30-day-old knockout animals reversed some, but not all, morpho-logical and biochemical phenotypes. Those that did not reverse include luminal diameters of proximal and distal caput and cau-da epididymis, the percentage of ciliated principal cells in caput epididymis, and nuclear AR localization. In summary, while our results reaffirm that androgens are important for normal epidid-ymal morphology and function, they indicate that LH could be required for certain facets of epididymal morphology and/or function. androgen receptor, epididymis, estrogen receptor, gene regula-tion, luteinizing hormon