TITLE:
Effect of Androstenedione on Adipogenesis in Murine C3H10T1/2 Mesenchymal Cells
AUTHORS:
Pandurangan Ramaraj, Jorge N. Artaza, Indrani Sinha-Hikim, Wayne E. Taylor
KEYWORDS:
Androstenedione, Adipogenesis, Myogenesis, Androgen Receptor, Bicalutamide
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.5 No.2,
February
9,
2015
ABSTRACT: Clinical trials of weak
androgen androstenedione (AD) administered at a high concentration, showed an
increase in muscle mass in men like strong androgens testosterone (T) and
dihydrotestosterone (DHT), but did not show any inhibitory effect on fat mass
unlike strong androgens. This observation prompted us to check the in-vitro effect of AD on adipogenesis
using mouse mesenchymal multipotent cells (C3H10T1/2),
which can differentiate into both myoblasts and adipocytes. Results indicated
that AD inhibited adipogenesis at 10 nM, 100 nM and 1 μM concentrations, but
not at 10 μM concentration. AD did not inhibit adipogenesis at 10 μM
concentration and also did not inhibitmyogenesis at 10 μM concentration.
Addition of bicalutamide, an androgen receptor (AR) antagonist decreased
myogenesis and increased adipogenesis, indicating that the effect of AD was
mediated through AR. Another weak androgen dehydroepiandrosterone (DHEA) also
showed the same pattern of adipogenesis in 10T1/2 cells. AD also showed a
similar pattern of adipogenesis in 3T3-L1 preadipocyte cells. Thus, the in-vitro results of AD on
adipogenesis correlated with the in-vivo results of AD on fat-mass from clinical trials and suggested a possible difference
in biological action between weak androgens (AD, DHEA) and strong androgens (T,
DHT) on adipogenesis. Since the biological action of AD was mediated through
AR, this physiological difference onadipogenesis could be due to the nature
(partial agonist/antagonist) of AD binding to AR.