Premium
Expression of 11β‐Hydroxysteroid Dehydrogenase Type 1 in the Human Hypothalamus
Author(s) -
Bisschop P. H.,
Dekker M. J. H. J.,
Osterthun W.,
Kwakkel J.,
Anink J. J.,
Boelen A.,
Unmehopa U. A.,
Koper J. W.,
Lamberts S. W. J.,
Stewart P. M.,
Swaab D. F.,
Fliers E.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12017
Subject(s) - hypothalamus , medicine , endocrinology , supraoptic nucleus , vasopressin , suprachiasmatic nucleus , arcuate nucleus , biology , immunocytochemistry , nucleus , glucocorticoid , 11β hydroxysteroid dehydrogenase type 1 , proopiomelanocortin , enzyme , microbiology and biotechnology , dehydrogenase , biochemistry
The hypothalamus is a major target for glucocorticoids and a key structure for hypothalamic‐pituitary‐adrenal ( HPA ) axis setpoint regulation. The enzyme 11β hydroxysteroid dehydrogenase type 1 (11β HSD 1) modulates glucocorticoid signalling in various tissues at the prereceptor level by converting biologically inactive cortisone to its active form cortisol. The present study aimed to assess 11β HSD 1 expression in the human hypothalamus. We studied 11β HSD 1 expression in five frozen and four formalin‐fixed, paraffin‐embedded human hypothalami (obtained from the Netherlands Brain Bank) by the polymerase chain reaction and immunocytochemistry, respectively. 11β HSD 1 mRNA was expressed in the area of the suprachiasmatic nucleus, which is the biological clock of the brain, in the supraoptic nucleus and paraventricular nucleus ( PVN ), and in the infundibular nucleus, which is the human homologue of the rodent arcuate nucleus. 11β HSD 1 was detected by immunocytochemistry in the same nuclei. In the PVN , neuronal 11β HSD 1 immunoreactivity colocalised with corticotrophin‐releasing hormone ( CRH ), arginine vasopressin and oxytocin, as shown by dual fluorescence staining. Our data demonstrate that 11β HSD 1 is widely expressed in the human hypothalamus. Its colocalisation with CRH in the PVN suggests a role in modulation of glucocorticoid feedback of the HPA axis, whereas the expression of 11β HSD 1 in additional and functionally diverse hypothalamic nuclei points to a role for the enzyme in the regulation of metabolism, appetite and circadian rhythms.