Chronic Haloperidol Treatment Increases the Level of in Vitro Translatable Messenger Ribonucleic Acid Coding for the β-Endorphin/drenocorticotropin Precursor Proopiomelanocortin in the Pars Intermedia of the Rat Pituitary

Höllt, Volker; Haarmann, I.; Seizinger, Bernd R.; Herz, A.

doi:10.1210/endo-110-6-1885

Cited by 93 publications

(24 citation statements)

References 21 publications

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“…These 3'-tailed probes hybridized with the same anatomical specificity as the 5'-labeled probe, regardless of tail length, indicating that longer tails should be used to increase probe specific activity. Furthermore, the 3H-labeled probe gave a strong discrete hybridization signal from cells in the pituitary anterior lobe, as reported previously for 3H-labeled POMC cDNA (14 (3,4,19), was also confirmed on a series of alternate tissue sections with a longer POMC cDNA. The high correlation (r = 0.96) between the hybridization OD values obtained using the two probes confirms the accuracy of the oligonucleotide probe in detecting a predicted change in mRNA levels.…”

Section: Resultssupporting

confidence: 86%

“…As a final test ofoligonucleotide probe specificity and to provide initial data on the usefulness of these probes in detecting the effects of in vivo treatment, pituitary sections from haloperidol-treated and control rats were hybridized with the 32P-labeled oligonucleotide or cloned cDNA probes used previously. As expected from previous studies (3,4,19), the hybridization signal in the Unlabeled ) is included as a control for specificity. The oligonucleotide was 32P-labeled at the 5' or 3' terminus.…”

Section: Resultsmentioning

confidence: 99%

“…In complex tissues, such as vertebrate nervous or endocrine systems, cell-specific regulation of gene expression often occurs. For example, in rat pituitary, proopiomelanocortin (POMC) mRNA levels are regulated by glucocorticoids only in the anterior lobe corticotrophs and by dopamine only in the intermediate lobe melanotrophs (1)(2)(3)(4)(5)(6)(7). Because of such subtle complexities, investigators have begun to study mRNA regulation at the single-cell level by in situ hybridization with cDNA (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) or complementary RNA (20) probes.…”

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confidence: 99%

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Detection of proopiomelanocortin mRNA by in situ hybridization with an oligonucleotide probe.

Lewis

Sherman

Burke

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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Synthetic oligonucleotide probes can be easily obtained and used, in contrast to cDNA cloning to develop probes, and thus the present study was carried out to determine whether such probes could also be useful for in situ hybridization. A 24-base synthetic oligonucleotide complementary to part of the a-melanocyte-stimulating hormone (a-MSH) coding region of proopiomelanocortin (POMC) mRNA was 5'-end-labeled by using [y-32P]ATP with T4 polynucleotide kinase or was 3' tailed by using [a-32P] (200-250 g; Charles River Breeding Laboratories) were anesthetized with sodium pentobarbital (150 mg/kg, i.p.) and perfused intracardially with 50 ml of ice-cold saline followed by cold 0.1 M phosphate-buffered 4% formaldehyde for 30 min (21). One group of animals (n = 6) had been treated with haloperidol (2 mg/kg per day, i.p.) or saline for 4 days prior to perfusion. Pituitaries were removed, postfixed in ice-cold buffered formaldehyde for 1 hr, and incubated overnight in 15% sucrose in 0.02 M phosphate-buffered saline (21) at 4°C. The tissues were then frozen in liquid N2, and 10-,um-thick sections were cut in a cryostat at -20°C, thaw-mounted onto gelatin-coated slides, and stored at -80°C.Probes

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Detection of proopiomelanocortin mRNA by in situ hybridization with an oligonucleotide probe.

Lewis

Sherman

Burke

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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“…Recently, it has been shown that in addition to having effects on POMC peptide secretion, dopaminergic compounds can also change IP content of POMC peptides (3,9). Chronic treatment of the rat with dopamine agonists or antagonists either decreases or increases, respectively, the amount of radioimmunoactive ,3endorphin or a-MSH in the IP.…”

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confidence: 99%

Regulation of the pro-opiomelanocortin mRNA levels in rat pituitary by dopaminergic compounds.

Chen¹,

Dionne²,

Roberts³

1983

Proc. Natl. Acad. Sci. U.S.A.

136

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Dopamine-containing neurons directly innervate the intermediate lobe of the pituitary and dopaminergic compounds exert inhibitory effects on the secretion and the content of a-melanocyte-stimulating hormone and P-endorphin in this tis-sue. In this study, we have investigated the effects of dopamine receptor agonists and antagonists on the level of pro-opiomelanocortin (POMG) mRNA in rat pituitary. RNAs isolated from neurointermediate pituitary (NIP) or anterior pituitary were spotted on nitrocellulose filters and the levels of POMC mRNA were quantified by hybridization to a POMC-specific complementary DNA probe coupled with autoradiography and densitometry. Administration of a dopamine receptor antagonist, haloperidol (2 mg/kg per day), to adult female rats resulted in a 3-to 5-fold increase in POMC mRNA level in the NIP. Treatment with the dopamine agonist 2-Br-a-ergocryptine (1 mg/kg per day) decreased significantly the content of POMC mRNA in the NIP. These drugs had no apparent effect on the POMC mRNA levels in the anterior pituitary. The effect of haloperidol and ergocryptine on POMC mRNA in the NIP is time-and dose-dependent. The elevation of POMC mRNA content in the NIP by haloperidol can be observed as early as 6 hr after treatment. These effects of dopaminergic compounds can also be demonstrated in adult male and ovariectomized female rats. The (-endorphin content of the NIP, as measured by radioimmunoassay, and the de novo synthesis of POMC, as determined by radioactive amino acid labeling and two-dimensional gel electrophoresis analysis, also show negative regulation by dopaminergic compounds.The monoamine neurotransmitter dopamine and its agonists have been shown to inhibit the release of ca-melanocyte-stimulating hormone (a-MSH) and ,B-endorphin, two pro-opiomelanocortin (POMC)-derived peptides, from the intermediate lobe (IP) of the rat pituitary (1-3). Dopamine antagonists, such as haloperidol, stimulate the release of a-MSH and ,B-endorphin (3,4). These effects on POMC-derived peptide secretion from the IP appear to be mediated through a D2 dopamine receptor on the IP melanotroph (for a review, see ref. 5). Dopamine-containing synaptic endings had been identified directly in the rat IP, suggesting direct neural control of IP POMC secretion (6). In the rat pituitary anterior lobe (AP), a tissue that also synthesizes and secretes POMC-derived peptides, dopaminergic agonists and antagonists have not been shown to have similar effects on POMC peptide secretion (1,7,8).Recently, it has been shown that in addition to having effects on POMC peptide secretion, dopaminergic compounds can also change IP content of POMC peptides (3, 9). Chronic treatment of the rat with dopamine agonists or antagonists either decreases or increases, respectively, the amount of radioimmunoactive ,3endorphin or a-MSH in the IP. Such observations would suggest.that these drugs have effects on POMC synthesis parallel to their effects on secretion. Indeed, a very recent study by Hollt et al. showed that chronic (7 day) ...

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“…As a result, dopamine receptor agonists inhibit and antagonists stimulate the biosynthesis and release of 8-endorphin (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

The Regulation of a Post-Translational Peptide Acetyltransferase: Strategies for Selectively Modifying the Biological Activity of Neural and Endocrine Peptides

Millington¹

1991

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Chronic Haloperidol Treatment Increases the Level of in Vitro Translatable Messenger Ribonucleic Acid Coding for the β-Endorphin/drenocorticotropin Precursor Proopiomelanocortin in the Pars Intermedia of the Rat Pituitary

Cited by 93 publications

References 21 publications

Detection of proopiomelanocortin mRNA by in situ hybridization with an oligonucleotide probe.

Detection of proopiomelanocortin mRNA by in situ hybridization with an oligonucleotide probe.

Regulation of the pro-opiomelanocortin mRNA levels in rat pituitary by dopaminergic compounds.

The Regulation of a Post-Translational Peptide Acetyltransferase: Strategies for Selectively Modifying the Biological Activity of Neural and Endocrine Peptides

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