Corticotropin-releasing factor and adrenocorticotrophic hormone as potential central mediators of OB effects.
OB (leptin) has been identified as a factor that suppresses appetite and stimulates metabolism. Attention has focused on the hypothalamus as its potential site of action, but OB could also act on other brain regions. In addition, the paradox of high OB levels in obese humans remains unresolved. Here we show in mice that both the long and short form of the OB receptor are expressed not only in the hypothalamus but also in the amygdala and pituitary. Recombinant murine OB elicited the release of corticotropin-releasing factor from superfused brain slice preparations containing hypothalamus or amygdala. Because corticotropin-releasing factor inhibits appetite and stimulates metabolism, it may be a key mediator of central OB effects. Recombinant OB also induced pituitary release of adrenocorticotrophic hormone. Because adrenocorticotrophic hormone-induced elevation of plasma glucocorticoid levels can inhibit corticotropin-releasing factor release via negative feedback, the OB effects on pituitary adrenocorticotrophic hormone release may be pertinent to human obesity, which combines increased plasma glucocorticoid levels with elevated levels of OB. An imbalance between the effects of OB on corticotropin-releasing factor release from the hypothalamus and on adrenocorticotrophic hormone release from the pituitary could contribute to obesity.
Raber
J
J
Gladstone Molecular Neurobiology Program and the Department of Neurology, University of California, San Francisco, California 94141-9100, USA. Jacob_Raber@quickmail.ucsf.edu
Chen
S
S
Mucke
L
L
Feng
L
L
D000324:Adrenocorticotropic Hormone / Q000502:physiology*; D000679:Amygdala / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D007031:Hypothalamus / Q000502:physiology; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
D002352:Carrier Proteins; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone