Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor

Abstract

Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human sex hormone binding globulin and to the bovine progestin receptor. APMIS 2000; 108:838+l6.For the steroidal growth promoters trenbolone acetate (TBA) and melengestrol acetate (MGA) neither the complete spectrum of biological activities nor the potential endocrine disrupting activity of their excreted metabolites in the environment is fully understood. The potency of these substances in [3H]dihydrotestosterone ([3H]-DHT) displacement from the recombinant human androgen receptor (rhAR) and from human sex-hormone binding globulin (hSHBG) was evaluated. In addition, the potency for [3H]-ORG2058 displacement from the bovine uterine progestin receptor (bPR) was tested. For comparison, different anabolics and synthetic hormones were also tested for their binding affinities. For 17ptrenbolone (1 7P-TbOH), the active compound after TBA administration, an affinity the rhAR similar to dihydrotestosterone (DHT) and a slightly higher affinity to the bPR than progesterone were demonstrated. The affinity of the two major metabolites, 17a-trenbolone and trendione, was reduced to less than 5% of the 17~-TbOH-value. The affinity of these three compounds and of MGA to the hSHBG was much lower compared with DHT. MGA showed a 5.3-fold higher affinity than progesterone to the bPR but only a weak affinity to the rhAR. The major MGA metabolites have an affinity to the bPR between 85% and 28% of the affinity of progesterone. In consequence, MGA and TBA metabolites may be hormonally active substances, which will be present in edible tissues and in manure. We conclude that detailed investigations on biodegradation, distribution and bio-efficacy of these substances are necessary.

Dihydrotestosterone is elevated following sprint exercise in healthy young men

“…This time scale of action is consistent with previous reports for testosterone (13), while adding DHT to the array of androgenic factors elevated in the acute phase response to exercise. The presence of elevated DHT during exercise may be of considerable significance given that DHT has a greater affinity than testosterone at the androgenic receptor and creates a more stable androgen-receptor complex (5,18). That these elevations were short lived may be of equal importance in determining their functional relevance.…”

Time of feeding and growth promotant effects on the winter growth performance and carcass traits of steers

“…There is a very narrow margin of profitability in the feedlot industry and the price paid for beef is a function of supply and demand for beef in the United States market, exchange rate on the dollar, and transportation costs. At the same time consumers have become more critical of the impact of modern food production practices on human and animal health and the environment (Bauer et al 2000;Schiffer et al 2001). To remain competitive the Canadian beef industry must explore new ways to reduce the cost of production.…”

Characterisation of gene expression patterns in 22RV1 cells for determination of environmental androgenic/antiandrogenic compounds

“…Complex influences on gene expression like induction of one gene and repression of another one cannot be covered by reporter-gene assays. The third method established are the binding assays [16][17][18][19] that allow studies on binding efficiencies only. No statement concerning a functional bioresponse can be made.…”

“…Competitive receptor assays have been established to measure binding affinities of different substances [16]. Recently, Bauer et al [17] succeeded in establishing a test system on the basis of recombinant human AR. These assays can be performed on whole cells or cell homogenates [18,19].…”