Steroid Production from Plasma Cholesterol. II.In VivoConversion of Plasma Cholesterol to Ovarian Progesterone and Adrenal C19and C21Steroids in Humans

Abstract

Tritiated cholesterol was injected intravenously into 3 ovulating women, 10, 14 and 23 days prior to tubal ligation. The specific activity of urinary pregnanediol (SA in dpm/μmole) was consistently lower than the SA of plasma free cholesterol of the corresponding day. This was observed in the luteal phase of 2 normal cycles and in 1 normal cycle prolonged with hCG from day 22 to day 31. This finding would suggest that the corpus luteum of a normal cycle as well as in early pregnancy produces progesterone from at least two sources, plasma cholesterol and probably newly formed cholesterol within the gland. The steroid production in the adrenal gland from plasma cholesterol was studied in a similar manner, by the determination of the SA of 2 C₂₁ urinary metabolites, tetrahydrocortisone and tetrahydrocortisol and 3 C₁₉ compounds, dehydroepiandrosterone, androsterone and etiocholanolone. The SA of all 5 compounds were similar to the SA of the corresponding plasma free cholesterol in the control periods of 3 subjects. With an increased endogenous ACTH production due to stress, the pattern was again similar (1 subject). Intramuscular injections of ACTH were given every 12 hr for at least 2 days in 2 subjects. The results were similar except for a slight decrease in the SA of all 5 compounds in one case where the tracer cholesterol had been administered only 6 days prior to the ACTH. These data suggest that hydrocortisone and adrenal C₁₉ compounds are derived almost exclusively from plasma free cholesterol even under ACTH stimulation.