Androgenic effects of the antiprogestagen RMI 12,936

Abstract

RMI 12,936 (7alpha-methyl-17beta-hydroxy-androst-5-en-one) was tested for androgenic activity in mouse kidney and for antiprogestational activity in guinea-pig uterus. RMI 12,936 stimulated an increase in kidney weight and in the activity of the androgen-responsive renal enzymes, beta-glucuronidase, alcohol dehydrogenase and arginase. RMI 12,936 was bound by the renal androgen receptor with a relative affinity approximately one-third that of testosterone. Although RMI 12,936 did not stimulate glycogen accumulation in guinea-pig endometrium in vivo, it was active in endometrial organ culture. When RMI 12,936 was combined with progesterone, glycogen accumulation in vitro was partly inhibited. RMI 12,936 was bound by the guinea-pig uterine progesterone receptor with a relative affinity of less than 1%. It is concluded that RMI 12,936 is an androgenic steroid with antifertility actions and in-vitro antiglycogenic activity.

Further investigation of the role of progesterone in the control of embryo transport in the mouse

“…RMI 12,936 is known to be metabolized in rats to 7a-methyl testosterone (Hardy, Kendle, Lawrie & Omand, 1977;Taylor & Kendle, 1978), and to exhibit marked androgenic properties (Bullock, Feil, Gupta, Demers & Bardin, 1978), while androgens are known to disrupt embryo transport and cause retention of embryos in mice (Burdick, Emerson & Whitney, 1940 (Kendle & Bennett, 1969). Appropriate groups were compared statistically using the Welch test (Welch, 1947 s.e.m.…”