Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims.
Suicidal behavior has been associated with hypothalamic-pituitary-adrenal overactivity in humans, as measured by increased corticosteroid secretion. To investigate whether this overactivity is reflected at the pituitary level, we have studied the localization of pro-opiomelanocortin (POMC) mRNA, and glucocorticoid receptor (GR) mRNA, in human anterior pituitaries, and quantified these messages relative to controls. Pituitaries from 7 suicide victims and 11 cardiac deaths were sectioned into 10-microns slides, stained with thionin and processed for in situ hybridization using a riboprobe complementary to human POMC mRNA. To correct for possible postmortem cell loss, hybridization with P1B15, a cDNA complementary to rat cyclophillin mRNA, was used in adjacent sections. POMC mRNA containing cells were found to be localized in clusters and were highly associated with corticotropin-releasing hormone (CRH) receptors. In contrast, GR mRNA containing cells were distributed through the pituitary, although areas of increased density were associated with POMC mRNA cells. Quantification with a computerized image analysis system revealed a 25% increase in POMC message in suicide victims. Analysis of the corticotrophic cell clumps showed that the suicide victims had higher POMC mRNA density per cell (p = 0.04) and larger corticotrophic cell size (p = 0.04) than the cardiac death victims. No differences in GR mRNA were detected between the two groups, although GR and POMC mRNA levels were highly and significantly correlated (r = 0.8, p < 0.001). There were no differences in P1B15 message between the two groups. We conclude that in situ hybridization is a useful tool to study gene regulation in human neuroendocrine tissue and that suicide victims show evidence of chronic hypothalamic-pituitary-adrenal axis activation.
López
J F
JF
Mental Health Research Institute, University of Michigan, Ann Arbor 48109.
Palkovits
M
M
Arató
M
M
Mansour
A
A
Akil
H
H
Watson
S J
SJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003346:Corticotropin-Releasing Hormone; D016757:Death, Sudden, Cardiac / Q000209:etiology; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009479:Neuropeptides / Q000032:analysis; D010902:Pituitary Gland / Q000737:chemistry*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D017981:Receptors, Neurotransmitter / Q000032:analysis; D013315:Stress, Psychological / Q000235:genetics*; D013405:Suicide; D013462:Sulfur Radioisotopes
D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D017981:Receptors, Neurotransmitter; D013462:Sulfur Radioisotopes; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone