Adrenergic receptors in premenstrual dysphoric disorder. II. Neutrophil β₂-adrenergic receptors: G(s) protein coupling, phase of menstrual cycle and prediction of luteal phase symptom severity

Abnormal β₂-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 β₂-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 Gs protein were determined from agonist-displacement experiments. Follicular β₂-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 β₂-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 β₂-adrenergic receptor binding measures were correlated with luteal symptom severity. These findings suggest abnormal β₂-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.