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Prolactin is an anterior pituitary hormone that regulates lactation, reproduction and growth. Transcription of the prolactin gene is under physiological inhibition by dopamine and other hormones (e.g. glucocorticoids), however, mechanisms underlying transrepression of the gene are not well understood. As hyperprolactinemia arising from prolactin-secreting tumors is a common pituitary disorder treated with synthetic dopamine agonists, defining the molecular basis for dopaminergic suppression of prolactin has clinical significance. The aim of this study is to identify signaling pathways and epigenetic events important for transrepression of prolactin. The data show that activation of dopamine D2 receptors in prolactin-secreting cells strongly inhibits the function of kinase ERK1/2; this inhibition (mimicked by selective MEK1 inhibitors) leads to pronounced specific suppression of the endogenous prolactin gene and transfected prolactin promoter constructs. Chromatin immunoprecipitation analysis revealed for the first time that dopamine and MEK1 inhibitors rapidly reduce histone acetylation on the endogenous prolactin promoter, consistent with a role in suppression of the gene. In contrast to dopamine, the synthetic glucocorticoid dexamethasone, which inhibits prolactin transcription, stimulated the recruitment of glucocorticoid receptors to the prolactin genomic promoter. During the same time period (within 60 min), dexamethasone did not affect histone acetylation suggesting an alternate mechanism of transrepression. Because the histone deacetylase inhibitor trichostatin A significantly induced the expression of endogenous prolactin gene, I examined whether historic deacetylase/corepressor complexes might function as terminal mediators of dopamine signaling, leading to transrepression of the prolactin gene. Consistent with this model, dopamine triggered rapid recruitment of corepressor mSin3A and histone deacetylase HDAC2 to the prolactin promoter region. Finally, transcription factors known to regulate the prolactin gene were investigated for their roles in mediating the response to ERK inhibition. This analysis indicated that binding sites for Pit-1 could confer negative transcriptional regulation in response to ERK inhibition. Moreover, the ETS-domain repressor protein ERF which binds to elements in the prolactin promoter, undergoes nuclear translocation in prolactin-secreting cells following treatment with dopamine or MEK1 inhibitors. In conclusion, this study, by identifying and characterizing new steps in the D2 dopaminergic signaling pathway, provides new insight into mechanisms of prolactin gene repression.
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The human prolactin gene contains two separate promoter regions and transcriptional start sites. Synthesis of prolactin in pituitary lactotropes depends on the presence of the transcription factor, Pit-1, which is also involved in mediating hormonal regulation through binding to the “pituitary” promoter. Prolactin secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Prolactinomas have been linked to estrogen exposure in humans and animals. Abstract. Dopamine has been recognized as the primary regulator of prolactin (PRL) secretion in vivo for over 20 years (1,2).Hypothalamic dopamine is secreted from tuberoinfundibular neurons at the median eminence of the hypothalamus into the hypophyseal portal blood flow, which directly perfuses the pituitary gland, delivering dopamine at high concentration to anterior pituitary kauainenehcp.com by: 8. Start studying prolactin and growth hormone. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Search. -*only pituitary hormone under tonic inhibitory control* -can occur as part of multiple endocrine neoplasia type I (MEN type 1).
Progesterone Receptor Repression of Prolactin/Stat5-Mediated Transcription of the β-Casein Gene in by The Endocrine Society is under the control of progesterone and prolactin (PRL). Start studying Exam Review. Learn vocabulary, terms, and more with flashcards, games, and other study tools. elicit their physiological effect within the target cell's nucleus by initiating transcription and translation. Which of the following is not a peptide hormone? Endocrine Control of Growth and Metabolism 15 Terms. smicallen. Jul 07, · Prolactin (PRL), 2 a hormone of the lactogen/cytokine family, is produced in the anterior pituitary gland and exerts diverse cellular actions through its transmembrane receptors (PRLR) in several target tissues. Prolactin is a major factor in the proliferation and differentiation of breast epithelium and is the primary hormone in the stimulation and maintenance of lactation. prolactin-inhibiting hormone: [ hor´mōn ] a chemical transmitter substance produced by cells of the body and transported by the bloodstream to the cells and organs on which it has a specific regulatory effect. adj., adj hormo´nal. Hormones act as chemical messengers to body organs, stimulating certain life processes and retarding others.