Inhibition of peripheral aromatization in baboons by an enzyme-activated aromatase inhibitor (MDL 18,962)

Journal Article · Sun May 01 04:00:00 EDT 1988 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-122-5-2007· OSTI ID:7154420

Longcope, C; Femino, A; Johnston, J O

The peripheral aromatization ((rho)BM) of androstenedione (A) and testosterone (T) was measured before and after administration of the aromatase inhibitor 10-(2 propynyl)estr-4-ene-3,17-dione (MDL-18,962) to five mature female baboons, Papio annubis. The measurements were made by infusing (3H)androstenedione/(14C)estrone or (3H)testosterone/(14C)estradiol for 3.5 h and collecting blood samples during the infusions and all urine for 96 h from the start of the infusion. Blood samples were analyzed for radioactivity as infused and product steroids, and the data were used to calculate MCRs. An aliquot of the pooled urine was analyzed for the glucuronides of estrone and estradiol and used to calculate the (rho)BM. MDL-18,962 was administered as a pulse in polyethylene glycol-400 (1-5 ml) either iv or via gastric tube 30 min before administration of the radiolabeled steroids. Control studies were done with and without polyethylene glycol-400 administration. When MDL-18,962 was given iv at 4 mg/kg, the aromatization of A was decreased 91.8 +/- 0.9% from the control value of 1.23 +/- 0.13% to 0.11 +/- 0.01%. At the same dose, aromatization of T was decreased 82.0 +/- 7.1%, from a control value of 0.20 +/- 0.03% to 0.037 +/- 0.018%. When MDL-18,962 was given iv at doses of 0.4, 0.1, 0.04, and 0.01 mg/kg, the values for aromatization of A were 0.16 +/- 0.03%, 0.18 +/- 0.06%, 0.37 +/- 11%, and 0.65 +/- 0.09%, respectively. The administration of MDL-18,962 via gastric tube at 4 mg/kg as a pulse decreased the aromatization of A from 1.35 +/- 0.06% to 0.43 +/- 0.12%, an inhibition of 67.2 +/- 10.7%. When administered via gastric tube daily for 5 days at 4 mg/kg, the aromatization of A fell from 1.35 +/- 0.06% to 0.063 +/- 0.003%, an inhibition of 84.4 +/- 0.5%.

• Research Organization: Univ. of Massachusetts Medical School, Worcester (USA)
• OSTI ID: 7154420
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 122:5; ISSN ENDOA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANDROGENS
ANDROSTANES
ANDROSTENEDIONE
AROMATIZATION
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BODY FLUIDS
CARBON 14 COMPOUNDS
CHEMICAL REACTIONS
ENZYME INHIBITORS
ENZYMES
ESTRADIOL
ESTRANES
ESTROGENS
ESTRONE
FUNCTIONS
HORMONES
HYDROXY COMPOUNDS
INHIBITION
ISOMERASES
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
MATERIALS
ORGANIC COMPOUNDS
REACTION KINETICS
STEROID HORMONES
STEROIDS
TESTOSTERONE
TRACER TECHNIQUES
TRITIUM COMPOUNDS