Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims

Juan F. Lopez, M. Palkóvits, Mihaly Arato, Alfred Mansour, Huda Akil, Stanley J. Watson

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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-um 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 PI B15, 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.

Original languageEnglish
Pages (from-to)491-501
Number of pages11
JournalNeuroendocrinology
Volume56
Issue number4
DOIs
Publication statusPublished - 1992

Fingerprint

Pro-Opiomelanocortin
Glucocorticoid Receptors
Suicide
Messenger RNA
In Situ Hybridization
Thionins
Corticotropin-Releasing Hormone Receptors
Cell Size
Adrenal Cortex Hormones
Complementary DNA
Cell Count

Keywords

  • Gene expression
  • Glucocorticoid receptor
  • HPA axis
  • Proopiomelanocortin
  • Suicide

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Cellular and Molecular Neuroscience
  • Endocrine and Autonomic Systems
  • Neuroscience(all)

Cite this

Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims. / Lopez, Juan F.; Palkóvits, M.; Arato, Mihaly; Mansour, Alfred; Akil, Huda; Watson, Stanley J.

In: Neuroendocrinology, Vol. 56, No. 4, 1992, p. 491-501.

Research output: Contribution to journalArticle

Lopez, Juan F. ; Palkóvits, M. ; Arato, Mihaly ; Mansour, Alfred ; Akil, Huda ; Watson, Stanley J. / Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims. In: Neuroendocrinology. 1992 ; Vol. 56, No. 4. pp. 491-501.
@article{6f1081d6bacf493c9017f616950e3f0b,
title = "Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims",
abstract = "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-um 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 PI B15, 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.",
keywords = "Gene expression, Glucocorticoid receptor, HPA axis, Proopiomelanocortin, Suicide",
author = "Lopez, {Juan F.} and M. Palk{\'o}vits and Mihaly Arato and Alfred Mansour and Huda Akil and Watson, {Stanley J.}",
year = "1992",
doi = "10.1159/000126266",
language = "English",
volume = "56",
pages = "491--501",
journal = "Neuroendocrinology",
issn = "0028-3835",
publisher = "S. Karger AG",
number = "4",

}

TY - JOUR

T1 - Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims

AU - Lopez, Juan F.

AU - Palkóvits, M.

AU - Arato, Mihaly

AU - Mansour, Alfred

AU - Akil, Huda

AU - Watson, Stanley J.

PY - 1992

Y1 - 1992

N2 - 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-um 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 PI B15, 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.

AB - 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-um 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 PI B15, 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.

KW - Gene expression

KW - Glucocorticoid receptor

KW - HPA axis

KW - Proopiomelanocortin

KW - Suicide

UR - http://www.scopus.com/inward/record.url?scp=0026452610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026452610&partnerID=8YFLogxK

U2 - 10.1159/000126266

DO - 10.1159/000126266

M3 - Article

C2 - 1335553

AN - SCOPUS:0026452610

VL - 56

SP - 491

EP - 501

JO - Neuroendocrinology

JF - Neuroendocrinology

SN - 0028-3835

IS - 4

ER -