Glucocorticoid receptor function in rat pituitary intermediate lobe is inhibited by an endogenous protein.
Though glucocorticoids inhibit proopiomelanocortin (POMC) gene expression and POMC-derived peptide release from corticotroph cells of the anterior pituitary, the regulation of this gene by glucocorticoids is less clear in the melanotroph cell of the pituitary intermediate lobe. To examine the difference between glucocorticoid sensitivity of the anterior lobe (AL) and intermediate lobe (IL) of the pituitary we have examined glucocorticoid receptor (GR) status of these two tissues and the role glucocorticoids play in regulating IL POMC gene expression. The rate of in vivo GR gene transcription, measured by nuclear run-on assay was consistently higher in the pituitary neurointermediate lobe (NIL) compared with the AL of the same animals. On a concentration basis, cytoplasmic GR mRNA in the NIL was similar to that found in the AL, and GR binding using [3H]dexamethasone (DEX) as ligand demonstrated similar concentrations of specific [3H]DEX binding in acutely isolated AL and NIL tissues. The specific Type II corticosteroid receptor ligand RU28362 displaced [3H]DEX binding to levels equivalent to non-specific binding, thus indicating that DEX was binding only to Type II corticosteroid receptors. To assess the direct action of glucocorticoids on POMC gene expression, NIL cells were cultured for 7 days and then treated with DEX. One hour DEX treatment of NIL primary cultures had no effect on levels of POMC heteronuclear RNA levels; in contrast, DEX induced a rapid and potent inhibition of POMC heteronuclear RNA levels in cells treated with the protein synthesis inhibitor puromycin.(ABSTRACT TRUNCATED AT 250 WORDS)
Sheppard
K E
KE
Baker Medical Research Institute, Prahran, Victoria, Australia.
Autelitano
D J
DJ
Roberts
J R
JR
Blum
M
M
D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D002467:Cell Nucleus / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000187:drug effects*
D000732:Androstanols; D011965:Receptors, Glucocorticoid; D012313:RNA; D011333:Pro-Opiomelanocortin; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; D003907:Dexamethasone