Adrenergic receptors in premenstrual dysphoric disorder. II. Neutrophil β 2-adrenergic receptors: G s protein coupling, phase of menstrual cycle and prediction of luteal phase symptom severity

Abstract

Abnormal β 2-adrenergic receptor coupling to G s protein is implicated in depressive disorders. Steroid hormones and antidepressants modulate β-adrenergic receptor coupling, which may relate to the therapeutic efficacy of antidepressants. We examined β 2-adrenergic receptors in 18 patients with premenstrual dysphoric disorder (PMDD), in 15 control subjects during the follicular phase and in 12 patients during late luteal phase. Antagonist-measured receptor density, agonist-measured receptor density in the high- and low-conformational states and agonist affinity to both states were measured. Coupling indices to G s protein were determined from agonist-displacement experiments. Follicular β 2-adrenergic receptor density was higher in patients than in control subjects, with a trend for higher receptor density in the high-conformational state. The phase of menstrual cycle had no effect on β 2-adrenergic receptor regulation in PMDD. Exploratory correlations showed that the K L/ K H ratio was related to anxiety ratings in control subjects and % R H was correlated with symptom severity in patients. In patients, follicular β 2-adrenergic receptor binding measures were correlated with luteal symptom severity. These findings suggest abnormal β 2-adrenergic receptor regulation in PMDD. Further exploration of the role of β-adrenergic receptor kinase, sex steroid hormones and antidepressants on β-adrenergic receptor regulation in PMDD is warranted.