Metabolism of Androstenone, 17β-Estradiol and Dihydrotestosterone in Primary Cultured Pig Hepatocytes and the Role of 3β-Hydroxysteroid Dehydrogenase in This Process

Abstract

Steroids metabolism plays an important role in mammals and contributes to quality of pig meat. The main objective of this study was to identify metabolites of androstenone, 17β-estradiol and dihydrotestosterone using primary cultured pig hepatocytes as a model system. The role of 3β-hydroxysteroid dehydrogenase (3βHSD) in regulation of steroid metabolism was also validated using trilostane, a specific 3βHSD inhibitor. Steroid glucuronide conjugated metabolites were detected by liquid chromatography time of flight mass spectrometry (LC-TOF-MS). 3βHSD enzyme was essential for metabolism of androstenone to 5α-androst-16-en-3β-ol, which then formed androstenone glucuronide conjugate. Metabolism of 17β-estradiol was accompanied by formation of glucuronide-conjugated estrone and glucuronide-conjugated estradiol. The ratio of the two metabolites was around 5∶1. 3βHSD enzyme was not involved in 17β-estradiol metabolism. 5α-Dihydrotestosterone-17β-glucuronide was identified as a dihydrotestosterone metabolite, and this metabolism was related to 3βHSD enzyme activity as demonstrated by inhibition study.

Age‐related change of hepatic uridine diphosphate glucuronosyltransferase and sulfotransferase activities in male chickens and pigs

“…Androstenone is produced by testicular Leydig cells of pigs and regulated in a way similar to anabolic hormones (Claus et al, 1994). This steroid molecule is metabolized in porcine livers by 3b-hydroxysteroid dehydrogenase to b-androstenol and then forms more hydrophilic sulfo-and glucuronide conjugates through SULT and UGT (Doran et al, 2004;Sinclair et al, 2005;Nicolau-Solano et al, 2006;Chen et al, 2015). In porcine hepatocytes, the ratio of sulfation and glucuronidation of b-androstenol is about 1 to 2 (Sinclair et al, 2005).…”

Glucocorticoid receptor is involved in the differential expression of hepatic 3β‐hydroxysteroid dehydrogenase between barrows and boars at finishing stage

“…However, castrated pigs have decreased feed efficiency, growth rate, and lean meat production compared to intact boars (Lundstrom et al 2009), and this poses an animal welfare issue (Thun et al 2006). Androstenone is a major factor contributing to boar taint, which is synthesized in the testis and metabolized in the liver (Rasmussen & Ekstrand 2014;Robic et al 2014;Chen et al 2015). The enzyme 3b-hydroxysteroid dehydrogenase (3b-HSD) plays a key role in the hepatic metabolism that catalyzes androstenone to b-androstenol (Sinclair et al 2005;Rasmussen & Ekstrand 2014;Chen et al 2015).…”

“…Androstenone is a major factor contributing to boar taint, which is synthesized in the testis and metabolized in the liver (Rasmussen & Ekstrand 2014;Robic et al 2014;Chen et al 2015). The enzyme 3b-hydroxysteroid dehydrogenase (3b-HSD) plays a key role in the hepatic metabolism that catalyzes androstenone to b-androstenol (Sinclair et al 2005;Rasmussen & Ekstrand 2014;Chen et al 2015). Pigs with low hepatic expression and activity of 3b-HSD are accompanied by a reduced rate of androstenone clearance, increased accumulation of androstenone in adipose tissue and the development of boar taint (Doran et al 2004;Cue et al 2007;Rasmussen et al 2012a,b).…”

“…; Chen et al . ). The enzyme 3β‐hydroxysteroid dehydrogenase (3β‐HSD) plays a key role in the hepatic metabolism that catalyzes androstenone to β‐androstenol (Sinclair et al .…”

Detection and Validation Studies of Trace Metals, Protein and Steroid in Different Organs of Local and Brand Meat (Poultry, Cattle and Fish)

“…Steroid hormones help control metabolism, immune functions, inflammation, water and salt balance as well as development of sexual characteristics. They also regulate diverse physiological processes in target tissues and play key role in quality growth of mammals (Sato and Iemitsu, 2015;Chen et al, 2015). Some of these anabolic steroids are excessively used in veterinary and as an abusive drug by humans (Mesmer and Satzger, 1997).…”