Corticotropin-releasing hormone is produced by rat corticotropes and modulates ACTH secretion in a paracrine/autocrine fashion.

Pecori Giraldi F, Cavagnini F
The Journal of clinical investigation · 1998 · doi:10.1172/jci443 · PMID:9616219 · PMC508837
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This study demonstrates that rat corticotropes synthesize and secrete corticotropin-releasing hormone, which modulates adrenocorticotropic hormone secretion in a paracrine or autocrine fashion within the anterior pituitary.

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This study investigated the local production of corticotropin-releasing hormone within the anterior pituitary gland of adult rats. Using reverse transcription-PCR and immunocytochemistry, researchers identified CRH mRNA specifically in corticotropes and detected mature CRH peptide secretion in primary cell cultures. The administration of a CRH antibody or antagonist significantly reduced basal ACTH secretion and blunted responses to potassium and forskolin, indicating that intrapituitary CRH modulates hormone release through paracrine or autocrine mechanisms. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Anterior pituitary hormone secretion is mainly regulated by hypothalamic releasing factors, which reach the pituitary via portal vessels. It has been demonstrated recently that these peptides can also be produced by the pituitary itself, thus possibly modulating hormone secretion in a paracrine/autocrine fashion. The object of this study was to seek evidence for the synthesis and secretion of corticotropin-releasing hormone (CRH) within the anterior pituitary and to ascertain its biological relevance. Messenger RNA from adult rat anterior pituitary fragments and cell cultures was reverse transcribed and subjected to PCR amplification using primers specific to the rat CRH gene. As in the hypothalamus, a single 232-bp band was obtained. The correspondence of the amplified fragment to the sequence of the CRH gene was confirmed by Southern blotting and restriction enzyme digestion. Combined in situ reverse transcription-PCR amplification/immunocytochemistry demonstrated the presence of CRH mRNA in corticotropes. Medium from anterior pituitary primary cultures contained approximately 7 pg/microg protein of CRH immunoreactivity which presented the same chromatographic profile on HPLC as the mature CRH peptide. Incubation of anterior pituitary cells with an antibody directed against CRH markedly reduced basal ACTH secretion compared with serum-treated control wells (0.89+/-0.11 vs. 1.74+/-0.14 ng/200,000 cells in control wells after 1 h, P < 0.05; 1.17+/-0.10 vs. 2.16+/-0. 39 ng/200,000 cells after 2 h, P < 0.05; 1.45+/-0.12 vs. 3.12+/-0.61 ng/200,000 cells after 3 h, P < 0.05). Further, the ACTH response to potassium and to forskolin was markedly blunted by the CRH antiserum as well as by the CRH antagonist, alpha-helical CRH(9-41). In conclusion, this study demonstrates the presence of CRH mRNA in normal rat corticotropes and the secretion of the mature peptide by the anterior pituitary, pointing to the production of CRH at the site of its target cells. In addition, intrapituitary CRH contributes in a paracrine/autocrine fashion to ACTH secretion.
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Advertisement Research Article Free access | 10.1172/JCI443 Ospedale San Luca, IRCCS, Istituto Auxologico Italiano, 2nd Chair of Endocrinology, University of Milan, Milan, 20149 Italy. [email protected] Find articles by Giraldi, F. in: PubMed | Google Scholar Ospedale San Luca, IRCCS, Istituto Auxologico Italiano, 2nd Chair of Endocrinology, University of Milan, Milan, 20149 Italy. [email protected] Find articles by Cavagnini, F. in: PubMed | Google Scholar Published June 1, 1998 - More info Published in Volume 101, Issue 11 on June 1, 1998 J Clin Invest. 1998;101(11):2478–2484. https://doi.org/10.1172/JCI443. © 1998 The American Society for Clinical Investigation J Clin Invest. 1998;101(11):2478–2484. https://doi.org/10.1172/JCI443. © 1998 The American Society for Clinical Investigation Published June 1, 1998 - Version history - Abstract Anterior pituitary hormone secretion is mainly regulated by hypothalamic releasing factors, which reach the pituitary via portal vessels. It has been demonstrated recently that these peptides can also be produced by the pituitary itself, thus possibly modulating hormone secretion in a paracrine/autocrine fashion. The object of this study was to seek evidence for the synthesis and secretion of corticotropin-releasing hormone (CRH) within the anterior pituitary and to ascertain its biological relevance. Messenger RNA from adult rat anterior pituitary fragments and cell cultures was reverse transcribed and subjected to PCR amplification using primers specific to the rat CRH gene. As in the hypothalamus, a single 232-bp band was obtained. The correspondence of the amplified fragment to the sequence of the CRH gene was confirmed by Southern blotting and restriction enzyme digestion. Combined in situ reverse transcription-PCR amplification/immunocytochemistry demonstrated the presence of CRH mRNA in corticotropes. Medium from anterior pituitary primary cultures contained approximately 7 pg/microg protein of CRH immunoreactivity which presented the same chromatographic profile on HPLC as the mature CRH peptide. Incubation of anterior pituitary cells with an antibody directed against CRH markedly reduced basal ACTH secretion compared with serum-treated control wells (0.89+/-0.11 vs. 1.74+/-0.14 ng/200,000 cells in control wells after 1 h, P < 0.05; 1.17+/-0.10 vs. 2.16+/-0. 39 ng/200,000 cells after 2 h, P < 0.05; 1.45+/-0.12 vs. 3.12+/-0.61 ng/200,000 cells after 3 h, P < 0.05). Further, the ACTH response to potassium and to forskolin was markedly blunted by the CRH antiserum as well as by the CRH antagonist, alpha-helical CRH(9-41). In conclusion, this study demonstrates the presence of CRH mRNA in normal rat corticotropes and the secretion of the mature peptide by the anterior pituitary, pointing to the production of CRH at the site of its target cells. In addition, intrapituitary CRH contributes in a paracrine/autocrine fashion to ACTH secretion. - Version history - Version 1 (June 1, 1998): No description Advertisement Advertisement Copyright © 2026 American Society for Clinical Investigation ISSN: 0021-9738 (print), 1558-8238 (online)

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