Regulation of beta 1- and beta 3-adrenergic agonist-stimulated lipolytic response in hyperthyroid and hypothyroid rat white adipocytes.

Abstract

1. This study examined the effects of thyroid status on the lipolytic responses of rat white adipocytes to beta-adrenoceptor (beta-AR) stimulation. The beta 1- and beta 3-AR mRNAs and proteins were measured by Northern and saturation analyses, respectively. Glycerol production and adenyl cyclase (AC) activity induced by various non-selective and selective beta 1/beta 3-AR agonists and drugs which act distal to the receptor in the signalling cascade were measured in cells from untreated, triiodothyronine (T3)-treated and thyroidectomized rats. 2. The beta 3-AR density was enhanced (72%) by T3-treatment and reduced (50%) by introduction of a hypothyroid state while beta 1-AR number remained unaffected. The beta 1- and beta 3-AR density was correlated with the specific mRNA level in all thyroid status. 3. The lipolytic responses to isoprenaline, noradrenaline (beta 1/beta 3/beta 3-AR agonists) and BRL 37344 (beta 3-AR agonist) were potentiated by 48, 58 and 48%, respectively in hyperthyroidism and reduced by about 80% in hypothyroidism. 4. T3-treatment increased the maximal lipolytic response to the partial beta 3-AR (CGP 12177) and beta 1-AR (xamoterol) agonists by 234 and 260%, respectively, increasing their efficacy (intrinsic activity: 0.95 versus 0.43 and 1.02 versus 0.42). The maximal AC response to these agonists was increased by 84 and 58%, respectively, without changing their efficacy. 5. In the hypothyroid state, the maximal lipolytic and AC responses were decreased with CGP (0.17 +/- 0.03 versus 0.41 +/- 0.08 mumol glycerol/10(6) adipocytes; 0.048 +/- 0.005 versus 0.114 +/- 0.006 pmol cyclic AMP min-1 mg-1) but not changed with xamoterol. 6. The changes in lipolytic responses to postreceptor-acting agents (forskolin, enprofylline and dibutenyl cyclic AMP, (Bu)2cAMP) suggest the modifications on receptor coupling and phosphodiesterase levels in both thyroid states. 7. Thyroid status affects lipolysis by modifying beta 3-AR density and postreceptor events without changes in the beta 1-AR functionality.

• Authors: R Germack, A Starzec, G Y Perret
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 129 Issue 3 Pg. 448-56 (Feb 2000) ISSN: 0007-1188 [Print] England
• PMID: 10711342 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-1 Receptor Agonists
• Adrenergic beta-Agonists
• Propanolamines
• RNA, Messenger
• Receptors, Adrenergic, beta
• Receptors, Adrenergic, beta-3
• Colforsin
• Adenylyl Cyclases
• CGP 12177

Topics

• Adenylyl Cyclases (metabolism)
• Adipose Tissue (cytology, drug effects, metabolism)
• Adrenergic beta-1 Receptor Agonists
• Adrenergic beta-Agonists (pharmacology)
• Animals
• Blotting, Northern
• Cell Membrane (drug effects, metabolism)
• Colforsin (pharmacology)
• Hyperthyroidism (metabolism)
• Hypothyroidism (metabolism)
• Kinetics
• Lipolysis (drug effects)
• Male
• Propanolamines (metabolism)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, beta (drug effects)
• Receptors, Adrenergic, beta-3
• Thyroidectomy