J. Allan Campbell

Steroid binding specificity of the hamster uterine progesterone receptor.

The relative binding affinities (RBA) of 51 steroids were determined for the uterine progesterone receptor of the proestrous hamster. The receptor demonstrated a high specificity for progesterone; most structural modifications to the progesterone molecule resulted in a substantial reduction in binding affinity. Only six steroids had relative binding affinities similar to progesterone (RBA=100): 17 alpha-ethinyl-17 beta-methoxy-4-androsten-3-one (RBA=85); 6 alpha-fluoro-4-pregnene-3,20-dione (RBA=94); 17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione (RBA=96); 19-nor-4-pregnene-3,20-dione (RBA=110); 21-fluoro-4-pregnene-3,20-dione (RBA=119); and 17 alpha-ethinyl-17 beta-methoxy-4-estren-3-one (RBA=123).

Arrest of folliculogenesis and inhibition of ovulation in the monkey following weekly administration of progestins

Studies were undertaken in the rhesus monkey to determine whether development of a dominant ovarian follicle could be repeatedly arrested by the administration of a progestin on day 7 of the menstrual cycle, and then every 7 days thereafter regardless of menstrual bleeding history. Progesterone (7.5 mg), norethisterone (1.5 mg), and 17 alpha-ethinyl-17 beta-methoxy-7 alpha-methyl-4-estren-3-one (1.0 or 1.5 mg) effectively inhibited ovulation when injected intramuscularly once a week for 8 weeks. Orally administered STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-4,9-estradien-3-one, 1.0 mg) also inhibited ovulation. Two structurally related steroids (17 beta-methoxy-4-estren-3-one, 1.0 mg; and 17 beta-methoxy-7 alpha-methyl-4-estren-3-one, 1.5 mg) did not inhibit ovulation when given intramuscularly at the indicated doses. Although weekly administration of certain progestins effectively arrested follicular development and inhibited ovulation in the primate, the treatment was accompanied by disturbances in menstrual bleeding patterns.

Effect of 7α-Methylation on Biological Activities of Norethindrone

Summary A very substantial increase of oral gonadotropin inhibiting (34 X), pregnancy inhibiting (10 X) and uterotropic (24 X) potencies was observed for 7α-meth-y1-17 α-ethynyl-19-nortestosterone (U-13851) compared to 17-ethynyl-19-nortestosterone (norethindrone) even though progestational potency was not enhanced. Although anabolic and androgenic properties are greatly increased in some 7α-methyl derivatives of testosterone and 19-nortestosterone, U-13851 did not appear to produce a typical androgenic response in laboratory tests. The authors wish to express their appreciation to J. I. Northam for statistical analysis of data and to J. C. Cornette and A. D. Forbes for technical assistance.