Oestradiol and progesterone change beta3-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 beta3-adrenoceptors (beta3-AR). beta1/beta2-AR were also studied. DESIGN: Four groups of animals were considered. (i) control rats at thermoneutrality, (ii) cold-acclimated rats, to determine beta-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 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 were determined by binding studies using [3H]CGP-12177 as radioligand. RESULTS: Two populations of low and high binding affinities (K(d) 1.6 and 27.3 nmol/l) corresponding to beta3- and beta1/beta2-AR respectively were found at thermoneutrality. beta3-AR density was higher than that of beta1/beta2-AR (B(max) 419 and 143 fmol/mg protein respectively). Cold-acclimated rats showed a reduction of beta3-AR binding capacity (B(max) 308 fmol/mg protein). Oestradiol and progesterone reduced the density of beta3-AR to 167 and 185 fmol/mg protein respectively, while increasing their affinity for [3H]CGP-12177 (K(d) 9.5 and 4.0 nmol/l vs 16 nmol/l in cold-acclimated untreated rats). The density of beta1/beta2-AR was also reduced after oestradiol treatment (B(max) 51 fmol/mg protein). CONCLUSIONS: Both oestradiol and progesterone reduce the density of beta3-AR in brown adipose tissue (BAT) while increasing their affinity for [3H]CGP-12177. Oestradiol also reduces the density of beta1/beta2-AR whereas cold-acclimation reduces the density of beta3-AR.