RESTORATION OF LEYDIG-CELLS AFTER REPEATED ADMINISTRATION OF ETHANE DIMETHANESULFONATE IN ADULT RATS

Adult male rats were repeatedly treated with ethane dimethanesulfonate (EDS), an agent known to destroy Leydig cells selectively. Following a second injection, changes in serum testosterone levels and histologi cal and morphometric changes of Leydig cells showed the time course to be similar to those after the first treatment. The number and volume of Leydig cells markedly decreased at day 2, began to increase from da y 7, and recovered to the values of the control rats at day 30, concom itant with the changes of serum testosterone levels. Cells in the inte rstitial tissue labeled with bromodeoxyuridine markedly increased in n umber at day 2, gradually decreased thereafter, and returned to the va lues of the controls at day 14. During this period, cells undergoing m itosis were seen, their type unable to be determined, but were presume d to be regenerating Leydig cells. Even 30 days following four treatme nts with intervals of 30 days each, serum testosterone levels were the same as those in the controls. Also the numerical and volume densitie s of Leydig cells and the volume of an average Leydig cell were the sa me as those of the controls. Mitosis was observed in mature Leydig cel ls at this period, if any. It appears that new Leydig cells began to p roliferate by division earlier than 14 days after EDS, allowing that t here were several stages of proliferation, and that the source of reap pearing Leydig cells may not be a limited number of precursor cells, i mplying the presence of stem cells for Leydig cells.