Expression patterns of corticotropin-releasing factor, arginine vasopressin, histidine decarboxylase, melanin-concentrating hormone, and orexin genes in the human hypothalamus.
The hypothalamus regulates numerous autonomic responses and behaviors. The neuroactive substances corticotropin-releasing factor (CRF), arginine-vasopressin (AVP), histidine decarboxylase (HDC), melanin-concentrating hormone (MCH), and orexin/hypocretins (ORX) produced in the hypothalamus mediate a subset of these processes. Although the expression patterns of these genes have been well studied in rodents, less is known about them in humans. We combined classical histological techniques with in situ hybridization histochemistry to produce both 2D and 3D images and to visually align and quantify expression of the genes for these substances in nuclei of the human hypothalamus. The hypothalamus was arbitrarily divided into rostral, intermediate, and caudal regions. The rostral region, containing the paraventricular nucleus (PVN), was defined by discrete localization of CRF- and AVP-expressing neurons, whereas distinct relationships between HDC, MCH, and ORX mRNA-expressing neurons delineated specific levels within the intermediate and caudal regions. Quantitative mRNA signal intensity measurements revealed no significant differences in overall CRF or AVP expression at any rostrocaudal level of the PVN. HDC mRNA expression was highest at the level of the premammillary area, which included the dorsomedial and tuberomammillary nuclei as well as the dorsolateral hypothalamic area. In addition, the overall intensity of hybridization signal exhibited by both MCH and ORX mRNA-expressing neurons peaked in distinct intermediate and caudal hypothalamic regions. These results suggest that human hypothalamic neurons involved in the regulation of the HPA axis display distinct neurochemical patterns that may encompass multiple local nuclei.
Krolewski
David M
DM
Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
Medina
Adriana
A
Kerman
Ilan A
IA
Bernard
Rene
R
Burke
Sharon
S
Thompson
Robert C
RC
Bunney
William E
WE
Schatzberg
Alan F
AF
Myers
Richard M
RM
Akil
Huda
H
Jones
Edward G
EG
Watson
Stanley J
SJ
D000328:Adult; D000368:Aged; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism*; D001931:Brain Mapping; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007028:Hypothalamic Hormones / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D021621:Imaging, Three-Dimensional / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D012333:RNA, Messenger; D001127:Arginine Vasopressin; C019463:melanin-concentrating hormone; D003346:Corticotropin-Releasing Hormone; D006640:Histidine Decarboxylase