Utilization of dehydroepiandrosterone and its sulphate for oestrogen production by pregnant baboons (Papio papio).
The effect of varying maternal circulating 3beta-hydroxy-5-androsten-17-one (D) and its sulphate (DS) on urinary oestrogen (Oe) excretion by baboons was determined between 65 and 174 days gestation (term = 184 days). Oe (mainly oestrone) was determined by radioimmunoassay after enzymic hydrolysis of conjugates. Increments in Oe were estimated from the difference between Oe during 5 days pre- and post-treatment. Oestradiol-17beta (5 mg in 5.0 ml saline-ethanol, 1:1) administered iv increased (P less than 0.001) Oe by 2.46 +/- 0.71, 7 (mean, mg +/- SD, number of experiments). The response to 100 mg D (3.20 +/- 1.50, 7) was greater (P less than 0.001) than that due to 100 mg DS (0.03 +/- 0.75, 7). The response to DS was not different from that due to saline-ethanol alone (-0.05 +/- 0.27, 5). Betamethasone (9alpha-fluoro-11beta,17,21-trihydroxy-16beta-methyl-1,4-pregnadiene-3,20-dione) administration (3 mg bi-daily, im) caused an approximately 90% reduction in Oe within 4 days. In animals treated chronically with betamethasone the response due to 100 mg D (2.74 +/- 1.04, 5) was again greater (P less than 0.001) that that due to 100 mg DS (0.10 +/- 0.09, 5). ACTH (8 U or 40 U, im, N = 11) produced a variable but not significant mean change in Oe at either dose level. Metyrapone (300 mg every 4 h for 6 doses) increased (P less than 0.005) Oe (0.77 +/- 0.48, 5). It is concluded that in normal pregnant animals and those treated with betamethasone, in which endogenous levels of D and DS are presumably reduced, D is preferentially used over DS for oestrogen produced. Variations in DS availability do not produce marked changes in oestrogen production. This suggest that rapid increases in oestrogen production, as occur for example close to term, may result from increased availability of D rather than DS. The variable responses to ACTH and the increase in Oe following metyrapone administration are compatible with significant foetal contributions of oestrogen precursors, the production of which is under ACTH control.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology; D004958:Estradiol / Q000652:urine; D004967:Estrogens / Q000096:biosynthesis*; D004970:Estrone / Q000652:urine; D005260:Female; D000882:Haplorhini; D008797:Metyrapone / Q000494:pharmacology; D010215:Papio; D011247:Pregnancy; D011270:Pregnancy, Animal; D013997:Time Factors
D004967:Estrogens; D004970:Estrone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D001623:Betamethasone; D008797:Metyrapone