A direct androgenic involvement in the expression of human corticotropin-releasing hormone

A-M Bao; D F Fischer; Y-H Wu; E M Hol; R Balesar; U A Unmehopa; J-N Zhou; D F Swaab

doi:10.1038/sj.mp.4001800

A direct androgenic involvement in the expression of human corticotropin-releasing hormone

A-M Bao, D F Fischer, Y-H Wu, E M Hol, R Balesar, U A Unmehopa, J-N Zhou, D F Swaab

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.

Original language	English
Pages (from-to)	567-76
Number of pages	10
Journal	Molecular Psychiatry
Volume	11
Issue number	6
DOIs	https://doi.org/10.1038/sj.mp.4001800
Publication status	Published - Jun 2006

Keywords

Adult
Aged
Aged, 80 and over
Corticotropin-Releasing Hormone
Female
Humans
Male
Middle Aged
Mood Disorders
Paraventricular Hypothalamic Nucleus
Receptors, Androgen
Response Elements
Testosterone
Tissue Distribution
Journal Article
Research Support, Non-U.S. Gov't

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10.1038/sj.mp.4001800

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title = "A direct androgenic involvement in the expression of human corticotropin-releasing hormone",

abstract = "We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.",

keywords = "Adult, Aged, Aged, 80 and over, Corticotropin-Releasing Hormone, Female, Humans, Male, Middle Aged, Mood Disorders, Paraventricular Hypothalamic Nucleus, Receptors, Androgen, Response Elements, Testosterone, Tissue Distribution, Journal Article, Research Support, Non-U.S. Gov't",

author = "A-M Bao and Fischer, {D F} and Y-H Wu and Hol, {E M} and R Balesar and Unmehopa, {U A} and J-N Zhou and Swaab, {D F}",

year = "2006",

month = jun,

doi = "10.1038/sj.mp.4001800",

language = "English",

volume = "11",

pages = "567--76",

journal = "Molecular Psychiatry",

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T1 - A direct androgenic involvement in the expression of human corticotropin-releasing hormone

AU - Bao, A-M

AU - Fischer, D F

AU - Wu, Y-H

AU - Hol, E M

AU - Balesar, R

AU - Unmehopa, U A

AU - Zhou, J-N

AU - Swaab, D F

PY - 2006/6

Y1 - 2006/6

N2 - We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.

AB - We investigated the possibility of a direct action of androgens on the expression of the human corticotropin-releasing hormone (CRH), which plays a central role in the hypothalamic-pituitary-adrenal (HPA)-axis. Colocalization of CRH and nuclear/cytoplasmic androgen receptor (AR) was found in neurons of the paraventricular nucleus (PVN) in the human hypothalamus. A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE. Expression of AR in combination with testosterone repressed CRH promoter activity through the ARE. We conclude that androgens may directly affect CRH neurons in the human PVN via AR binding to the CRH-ARE, which may have consequences for sex-specific pathogenesis of mood disorders.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Corticotropin-Releasing Hormone

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Mood Disorders

KW - Paraventricular Hypothalamic Nucleus

KW - Receptors, Androgen

KW - Response Elements

KW - Testosterone

KW - Tissue Distribution

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/sj.mp.4001800

DO - 10.1038/sj.mp.4001800

M3 - Article

C2 - 16446741

SN - 1359-4184

VL - 11

SP - 567

EP - 576

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 6

ER -

A direct androgenic involvement in the expression of human corticotropin-releasing hormone

Abstract

Keywords

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