Ablation of pituitary pro-opiomelanocortin (POMC) cells produces alterations in hypothalamic POMC mRNA levels and midbrain mu opioid receptor bindingin a conditional transgenic mouse model

Citation
Y. Zhou et al., Ablation of pituitary pro-opiomelanocortin (POMC) cells produces alterations in hypothalamic POMC mRNA levels and midbrain mu opioid receptor bindingin a conditional transgenic mouse model, J NEUROENDO, 13(9), 2001, pp. 808-817
Citations number
55
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROENDOCRINOLOGY
ISSN journal
09538194 → ACNP
Volume
13
Issue
9
Year of publication
2001
Pages
808 - 817
Database
ISI
SICI code
0953-8194(200109)13:9<808:AOPP(C>2.0.ZU;2-L
Abstract
The hypothalamic-pituitary-adrenal (HPA) axis is regulated by stress-relate d excitatory inputs, and various inhibitory and negative-feedback controls by glucocorticoids and opioids, including pro-opiomelanocortin (POMC)-deriv ed peptides. The role of POMC-derived peptides of pituitary origin in the m odulation of brain POMC mRNA expression and opioid receptor binding was inv estigated using a line of transgenic mice that express a fusion gene compos ed of the pituitary expression-specific promoter region of the POMC gene dr iving the herpes simplex viral-1 thymidine kinase (TK). Male adult mice wer e treated with the antiherpes agent ganciclovir that selectively ablates ce lls expressing TK. Following treatment, POMC mRNA levels, measured by quant itative solution hybridization/RNase protection assays, were decreased by 4 8% in the pituitary of the TK+/+ mice, reflecting an expected loss of the p ituitary corticotrope POMC cells. This treatment also significantly lowered pituitary beta -endorphin immunoreactivity content and plasma concentratio ns of corticosterone. In contrast, POMC mRNA levels were increased by 79% i n the hypothalamus of the TK+/+ mice with pituitary POMC cell ablation. Bin ding of [H-3]DAMGO to mu opioid receptors, as measured by quantitative auto radiography, was significantly reduced in several brain regions including t he central grey, median raphe and superficial grey layer of the superior co lliculus. These regions are innervated by hypothalamic POMC neurones. No si gnificant differences in binding to either kappa or delta opioid receptors were found in the brain regions studied. These results suggest that POMC-de rived peptides of pituitary origin may exert a tonic negative-feedback effe ct on hypothalamic POMC neurones. In turn, the downregulation of central mu opioid receptors in this model may be mediated through a mechanism related to hypothalamic POMC overexpression.