Glucocorticoid Receptor Function in Rat Pituitary Intermediate Lobe is Inhibited by an Endogenous Protein

Abstract

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)

Changes in glucocorticoid receptor mRNA in the developing ovine pituitary and the effects of exogenous cortisol

“…Exposure time: 15 days. pars intermedia has been reported (Bertini et al 1989 (Sheppard et al 1993). In the pars intermedia of the fetal sheep, POMC mRNA is translated and processed to immunoreactive ACTH (Matthews et al 1994).…”

“…Analysis of the developing rat pituitary revealed high levels of GR mRNA in the pars distalis, specifically in cells exhibiting ACTH immuno¬ reactivity (Cintra et al 1993). GR immunoreactivity is also present in the rat pars intermedia (Bertini et al 1989), and glucocorticoids have been shown to regulate pro¬ opiomelanocortin (POMC) heteronuclear RNA and mRNA in this region (Seger et al 1988, Sheppard et al 1993, indicating the presence and function of GRs in this region of the gland.…”

Glucocorticoid Regulation of Hypothalamic Proopiomelanocortin

“…The regulation of POMC transcription, however, is tissue specific. The inability of glucocorticoids to affect POMC in the intermediate lobe of the pituitary can be attributed to the absence of functional glucocorticoid receptors on these intermediate lobe cells, although glucocorticoid receptor mRNA has been detected in these cells [22, 23]. Functional glucocorticoid receptors can be induced in these cells if the neural input to the intermediate is disrupted [22, 24].…”

Glucocorticoids, but not Dopamine, Negatively Regulate the Melanotrophic Activity of the Rabbit Pituitary Intermediate Lobe

“…Cells were then incubated in the absence (a-c) or presence (d-f) of 1 nM OT for 2 h. The bars correspond to the meanf SEM of 3 experimental wells within the same experiment. Significant statistical differences (Pc0.05) were observed between the following groups: (a) vs (b), (b) vs (c) and (c) vx (d).detected low levels of immunoreactive GR on rat melanotrophs, Sheppard et a/ (35). demonstrated that these receptors lacked functional activity, since their ability to regulate POMC gene expression was blocked by the presence of inhibitory proteins.…”