The effects of l-thyroxine and dexamethasone on steroid dynamics in male cynomologous monkeys.
Male cynomologous monkeys (M. fascicularis) were infused with [3H]androgens, [14C]estrogens and [3H]cortisol before and after the administration of l-thyroxine, (l-T4) 150 micrograms/day for 6 wk, dexamethasone 8 mg every 8 h for 3 doses and dexamethasone 1.0 mg/day for 8 days. Blood samples were obtained before each of the infusions and analyzed for endogenous T, A, E1, E2 and F concentrations, % free T and % free E2, sex hormone-binding globulin (SHBG) and cortisol binding globulin (CBG) capacity. When l-T4 was being administered, T4 and triiodothyronine (T3) concentrations were also measured. Blood samples were obtained during the infusions and analyzed for radioactivity as testosterone (T), androstenedione (A), dihydrotestosterone (DHT), estradiol (E1), estrone (E2), and cortisol (F). All urine was collected for 96 h and an aliquot of the pooled urine was analyzed for radioactivity as estrone and estradiol glucuronide. The administration of l-T4 for 6 wk to 3 monkeys resulted in a marked rise in T4 and T3 levels, from 4.8 +/- 0.4 micrograms/dl and from 136 +/- 6 to 515 +/- 71 ng/dl, respectively. MCRT, MCRE2 and MCRE1 did not change, but MCRA values increased slightly and MCRF increased 2-3 fold. [rho]T.E2 did not change but [rho]A.E1BM showed a slight but significant increase. The inter-conversions between the androgens and between the estrogens were not altered. There was a 2-3-fold increase in SHBG and a decrease in %FT but no change in %FE2 or CBG. The concentrations of T, A and DHT rose but there was no trend in the levels of the estrogens. The administration of dexamethasone 8 mg every 8 h for 3 doses or 1 mg/day for 8 days caused no changes in the MCRs for T, A, E1 and E2 but did cause a significant decrease in MCRF. Measurement of splanchnic and peripheral tissue extractions before and after acute dexamethasone administration in 1 monkey showed that the decrease in MCRF was the result of a marked decrease, 11-2%, in splanchnic extraction of F. The extractions of T and E2 were relatively unaffected. The concentrations of T and F fell but E2 remained the same. % FT and % FE2 rose slightly and the concentrations of SHBG and CBG were unchanged. The androgen interconversions and estrogen interconversions were not affected but [rho]T,E2BM and [rho]A,E1BM showed slight decreases.(ABSTRACT TRUNCATED AT 400 WORDS)
Bourget
C
C
Department of Obstetrics and Gynecology, University of Massachusetts Medical School, Worcester 01605.
Femino
A
A
Franz
C
C
Hastings
S
S
Longcope
C
C
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D002250:Carbon Radioisotopes; D003907:Dexamethasone / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism*; D006854:Hydrocortisone / Q000378:metabolism*; D008251:Macaca / Q000378:metabolism*; D008252:Macaca fascicularis / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D013329:Structure-Activity Relationship; D013974:Thyroxine / Q000494:pharmacology*; D014316:Tritium
D000728:Androgens; D002250:Carbon Radioisotopes; D004967:Estrogens; D014316:Tritium; D003907:Dexamethasone; D013974:Thyroxine; D006854:Hydrocortisone