Oestradiol and progesterone change β3-adrenergic receptor affinity and density in brown adipocytes

Abstract

Objective: To check if the oestradiol- and progesterone-driven reduction in noradrenaline responsiveness of brown adipocytes is due to a reduction in either the density or the affinity of β3-adrenoceptors (β3-AR). β1/β2-AR were also studied. Design: Four groups of animals were considered. (i) control rats at thermoneutrality, (ii) cold-acclimated rats, to determine β-AR under continuous sympathetic stimulation, which is known to decrease noradrenaline responsiveness. (iii) oestradiol- and (iv) progesterone-treated cold-acclimated rats to determine hormonal effects on β-AR populations in thermogenically active brown adipocytes. Methods: Oestradiol and progesterone were chronically elevated by means of s.c. Silastic implants. Densities and affinities of β-AR populations were determined by binding studies using [3H]CGP-12177 as radioligand. Results: Two populations of low and high binding affinities (Kd 1.6 and 27.3 nmol/l) corresponding to β3- and β1/β2-AR respectively were found at thermoneutrality. β3-AR density was higher than that of β1/β2-AR (Bmax 419 and 143 fmol/mg protein respectively). Cold-acclimated rats showed a reduction of β3-AR binding capacity (Bmax 308 fmol/mg protein). Oestradiol and progesterone reduced the density of β3-AR to 167 and 185 fmol/mg protein respectively, while increasing their affinity for [3H]CGP-12177 (Kd 9.5 and 4.0 nmol/l vs 16 nmol/l in cold-acclimated untreated rats). The density of β1/β2-AR was also reduced after oestradiol treatment (Bmax 51 fmol/mg protein). Conclusions: Both oestradiol and progesterone reduce the density of β3-AR in brown adipose tissue (BAT) while increasing their affinity for [3H]CGP-12177. Oestradiol also reduces the density of β1/β2-AR whereas cold-acclimation reduces the density of β3-AR.