While at the hypothalamic level the interregulations of DA and 5-HT systems are complex and not fully understood, preclinical studies have shown that dopamine D2 receptors stimulate the release of hypothalamic

TRH and inhibit. TSH production at the pituitary level. In turn, TRH and thyroid Selleckchem Temsirolimus hormones stimulate the DA system, and induce a downregulation of D2 receptors. To examine the functional relationships between HPT axis activity and DA function in Inhibitors,research,lifescience,medical depressed patients, especially in those with a history of suicidal behavior, we measured hormonal responses to 8 am and 11 pm TRH tests and to apomorphine (APO) test in 64 drug-free inpatients with DSM-FV 12 major depression (35 with a history of suicide attempt, 29 without) and 34 hospitalized healthy controls. APO, a direct-acting DA agonist with high Inhibitors,research,lifescience,medical affinities for D2 and D3 receptors and a partial agonist at the D1 receptor, decreases PRL and

stimulates growth hormone (GH), ACTH, and Cortisol secretion.22 Compared with controls, patients demonstrate lower TRH and TSH responses and lower APO-induced PRL suppression (Table III). PRL response to APO provides an indirect index of central neurotransmission by assessing postsynaptic D2 receptor sensitivity at the pituitary level. A lower PRL response to APO may reflect a decreased D2 receptor function. This abnormality may represent (i) a primary deficit in D2 receptor Inhibitors,research,lifescience,medical sensitivity in the pituitary in depressed patients; or (ii) a downregulation of D2 receptors secondary to increased presynaptic DA activity. Cooccurrence of HPT axis and tuberoinfundibular DA dysregulation is compatible with a decreased TRH and D2 receptor function, Inhibitors,research,lifescience,medical possibly secondary to increased TRH tone, since TRH stimulates the DA system and induces a downregulation of D2 receptors. Table III. Demographic characteristics and biological data for depressed patients and normal control subjects. Δ, peak concentration minus baseline value; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone; PRL, prolactin; PRL suppression … When classifying Inhibitors,research,lifescience,medical patients according to

their history of suicidal behavior, those with a negative history more frequently have reduced AATSH values (Figure 3), but comparable hormonal APO responses (ie, PRL, ACTH, and Cortisol), than those with a positive history. In patients without a history of suicide attempt, a negative correlation is Suplatast tosilate found between AATSH values and post- APO ACTH (p=-0.44, P=0.02) and Cortisol (p=-0.50,P<0.008) levels. This correlation is found neither in patients with a history of suicide attempt (Figure 4) nor in control subjects. Figure 3 Differences between 11 pm and 8 am maximum increments in thyroid-stimulating hormone (ΔΔTSH) in controls and in depressed patients with a suicidal history (SH) and without an SH. Blunted ΔΔTSH, defined as a response below …