Adrenergic receptors in premenstrual dysphoric disorder. II. Neutrophil beta2-adrenergic receptors: Gs protein coupling, phase of menstrual cycle and prediction of luteal phase symptom severity.
Abnormal beta2-adrenergic receptor coupling to Gs protein is implicated in depressive disorders. Steroid hormones and antidepressants modulate beta-adrenergic receptor coupling, which may relate to the therapeutic efficacy of antidepressants. We examined beta2-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 beta2-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 beta2-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 beta2-adrenergic receptor binding measures were correlated with luteal symptom severity. These findings suggest abnormal beta2-adrenergic receptor regulation in PMDD. Further exploration of the role of beta-adrenergic receptor kinase, sex steroid hormones and antidepressants on beta-adrenergic receptor regulation in PMDD is warranted.
Gurguis
G N
GN
The Department of Veterans Affairs Medical Center, Dallas, TX, USA.
Yonkers
K A
KA
Blakeley
J E
JE
Phan
S P
SP
Williams
A
A
Rush
A J
AJ
D000328:Adult; D001007:Anxiety / Q000097:blood / Q000503:physiopathology*; D016022:Case-Control Studies; D003863:Depression / Q000097:blood / Q000503:physiopathology*; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007508:Irritable Mood / Q000502:physiology; D008183:Luteal Phase / Q000502:physiology; D008875:Middle Aged; D010869:Pindolol / Q000031:analogs & derivatives; D011293:Premenstrual Syndrome / Q000097:blood / Q000503:physiopathology*; D011485:Protein Binding / Q000502:physiology; D011869:Radioligand Assay; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000502:physiology*; D012044:Regression Analysis; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000502:physiology
D007457:Iodine Radioisotopes; D018343:Receptors, Adrenergic, beta-2; D020120:Iodocyanopindolol; D010869:Pindolol; D019204:GTP-Binding Proteins