Life-long serotonin reuptake deficiency results in complex alterations in adrenomedullary responses to stress.
This study examined whether serotonin transporter (SERT) deficiency influences adrenal serotonin (5-HT), catecholamine and Angiotensin II (Ang II) systems, and the hormonal response to acute restraint stress. Control SERT mice (+/+) expressed high numbers of SERT binding sites in adrenal medulla. Fifteen minutes of restraint stress increased adrenal 5-HT, adrenomedullary tyrosine hydroxylase (TH) mRNA expression and plasma epinephrine (EPI), and norepinephrine levels without alterations in adrenal catecholamine content. In SERT+/+, these responses coincided with a significant increase in adrenomedullary Ang II AT(2) receptor expression. SERT-deficient mice did not express SERT binding sites; their adrenal 5-HT was significantly depleted and further reduced after stress. They had exaggerated stress-induced EPI release into plasma, the increase in TH transcription did not occur, adrenal catecholamine content was decreased compared with SERT+/+, and stress induced a reduction rather than increase in the number of adrenomedullary AT(2) receptors. SERT-/- mice also possessed decreased pituitary 5-HT. Their pituitary ACTH was reduced after stress, but stress-induced increases in plasma ACTH and corticosterone were not different from those of SERT+/+ mice. Our results indicate that SERT function not only restrains stress-induced EPI release but also is required for the increase in adrenal catecholamine synthesis and AT(2) receptor expression.
Tjurmina
Olga A
OA
Laboratory of Clinical Science, NIMH, NIH, Bldg 10, Rm 3D41, 10 Center Dr., Bethesda, MD 20892, USA. ot3d@nih.gov
Armando
Ines
I
Saavedra
Juan M
JM
Li
Qian
Q
Murphy
Dennis L
DL
D000313:Adrenal Medulla / Q000378:metabolism / Q000503:physiopathology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D004837:Epinephrine / Q000097:blood; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine; D004837:Epinephrine