Oestradiol and progesterone change beta(3)-adrenergic receptor affinity and density in brown adipocytes

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 beta (3)-adrenoceptors (beta (3)-AR). beta (1)/beta (2)-AR were also studied. Design: Four groups of animals were considered. (i) control rats at thermon eutrality, (ii) cold-acclimated rats, to determine beta -AR under continuou s sympathetic stimulation, which is known to decrease noradrenaline respons iveness, (iii) oestradiol- and (iv) progesterone-treated cold-acclimated ra ts to determine hormonal effects on beta -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 beta -AR populations we re determined by binding studies using [H-3]CGP 12177 as radioligand. Results: Two populations of low and high binding affinities (K-d 1.6 and 27 .3 nmol/l) corresponding to beta (3)- and beta (1)/beta (2)-AR respectively were found at thermoneutrality. beta (3)-AR density was higher than that o f beta (1)/beta (2)-AR (B-max 419 and 143 fmol/mg protein respectively). Co ld-acclimated rats showed a reduction of beta (3)-AR binding capacity (B-ma x 308 fmol/mg protein). Oestradiol and progesterone reduced the density of beta (3)-AR to 167 and 185 fmol/mg protein respectively, while increasing t heir affinity for [H-3]CGP-12177 (K-d 9.5 and 4.0 nmol/l vs 16 nmol/l in co ld-acclimated untreated rats). The density of beta (1)/beta (2)-AR was also reduced after oestradiol treatment (B-max 51 fmol/mg protein). Conclusions: Both oestradiol and progesterone reduce the density of beta (3 )-AR in brown adipose tissue (BAT) while increasing their affinity for [H-3 ]CGP-12177. Oestradiol also reduces the density of beta (1)/beta (2),AR whe reas cold-acclimation reduces the density of beta (3)-AR.