Effect of androgens and progestins on mouse kidney cells: An in vitro model distinct from that of intact kidney

Abstract

Androgen metabolism in cultured mouse kidney cells was studied. Kidneys from Balb/C mice were dispersed with trypsine and the resulting cell suspension grown to confluent monolayers by 12–14 days in the presence of fetal calf serum. Cultured kidney cells had sufficient 5α-reductase to metabolize testosterone to dihydrotestosterone and 5α-androstanediols. This is in marked contrast to the mouse kidney in vivo which contains little or no 5α-reductase activity. The presence of an androgen receptor was suggested by the saturable uptake of testosterone in cultured kidney cells. When testosterone was added to the growth medium, total DNA, protein and β-glucuronidase activity increased 2–3-fold in a dose-dependent fashion with a half-maximal response at 2 × 10 −9 M testosterone. A specific effect on β-glucuronidase activity was shown by the increase of the β-glucuronidase/DNA ratio. Dihydrotestosterone and, to a lesser extent, the androstanediols had a similar effect. This is in marked contrast to the in vivo effects of androgens which produce a 20–50-fold increase in β-glucuronidase activity and no increase in DNA synthesis. In addition to androgens, 3 progestational steroids which are known to bind to the androgen receptor (progesterone, medroxyprogesterone acetate and cyproterone acetate) also stimulated renal cell cultures. It is concluded that primary cultures of mouse kidney cells metabolize testosterone and respond to both androgens and progestins. However, the metabolism and actions of androgens in primary kidney cells were markedly different from in vivo effects. The presence of the following features distinguishes the cultured renal cells from those in the intact kidney: presence of 5α-reductase; androgen-induced DNA synthesis; and blunted β-glucuronidase response.