Pit-1-dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth

Lin, Chijen; Lin, Sheng-Cai; Chang, Chia-Ping; Rosenfeld, Michael G.

doi:10.1038/360765a0

Cited by 311 publications

(174 citation statements)

References 33 publications

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“…Recent studies have provided information on the molecular basis of the specific regulation of PRL and GH gene transcription that could play an important role in the process of transdifferentiation. It was suggested that Pit-1 expression may directly or indirectly regulate somatotrophs and lactotrophs through activation of GRH and somatostatin receptors on the one hand and of dopamine on the other hand (35)(36)(37). In addition to Pit-1, other transcription factors and homeobox genes may be required for generating various pituitary cell phenotypes belonging to the Pit-1 lineage (38 -40).…”

Section: Discussionmentioning

confidence: 99%

Reversible Transdifferentiation: Interconversion of Somatotrophs and Lactotrophs in Pituitary Hyperplasia

et al. 2001

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Previous studies conclusively demonstrated transformation of somatotrophs into bihormonal mammosomatotrophs in gestational lactotroph hyperplasia during pregnancy. Similar transdifferentiation of somatotrophs into thyrotrophs through bihormonal intermediate thryrosomatotrophs was documented during thyrotroph hyperplasia in both rodent and human pituitaries in hypothyroidism. The cessation of the stimulation resulted in reversal of the process in both conditions. The conversion of lactotrophs into somatotrophs was suggested but not documented previously in the human gland. The present study was undertaken to investigate cases of somatotroph hyperplasia by transmission electron microscopy, immunoelectron microscopy using double immunogold labeling for growth hormone and prolactin, as well as combined immunocytochemistry and in situ hybridization. Adenohypophysial tissue was removed from a 38-year-old man and a 29-year-old woman with longstanding acromegaly due to ectopic overproduction of growth hormone-releasing hormone (GRH) by bronchial carcinoid tumors. For comparison, two pituitary biopsies were studied: one from a 38-year old woman with idiopathic lactotroph hyperplasia and one from a 14-year-old boy with secondary lactotroph hyperplasia due to a suprasellar craniopharyngioma. In the patients with somatotroph hyperplasia, the prevailing cell type was the hyperplastic somatotroph joined by mammosomatotroph deriving from lactotrophs, whereas monohormonal lactotrophs were rare. The predominance of mammosomatotrophs and active lactotrophs was documented in the patient with idiopathic lactotroph hyperplasia, whereas the case of the patient with secondary lactotroph hyperplasia was characterized by monohormonal lactotrophs and somatotrophs, but mammosomatotrophs were rare. That finding in the pituitary of the boy suggests that participation of mammosomatotrophs in lactotroph hyperplasia is not unconditional. Our findings conclusively demonstrate conversion of lactotrophs into mammosomatotrophs during somatotroph hyperplasia, providing further evidence for the potential of reversible transdifferentiation between somatotrophs and lactotrophs in response to functional demand.

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Section: Discussionmentioning

confidence: 99%

Reversible Transdifferentiation: Interconversion of Somatotrophs and Lactotrophs in Pituitary Hyperplasia

et al. 2001

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“…Members of the clusters specify position along axes in an embryo and limbs (1). Besides these clustered homeobox genes, certain of the unclustered and more divergent homeobox genes have been assigned roles in growth control, organogenesis, or establishment of cellular phenotypes (2)(3)(4)(5). Indeed, one of the unclustered homeobox gene, HOX11 (6)(7)(8)(9), controls the genesis of spleen (10,11).…”

Section: Introductionmentioning

confidence: 99%

A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.

Hatano¹,

Aoki²,

Dezawa³

et al. 1997

J. Clin. Invest.

112

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The Ncx/Hox11L.1 gene, a member of the Hox11 homeobox gene family, is mainly expressed in neural crest-derived tissues. To elucidate the role of Ncx/Hox11L.1, the gene has been inactivated in embryonic stem cells by homologous recombination. The homozygous mutant mice were viable. These mice developed megacolon with enteric ganglia by age 3-5 wk. Histochemical analysis of the ganglia revealed that the enteric neurons hyperinnervated in the narrow segment of megacolon. Some of these neuronal cells degenerated and neuronal cell death occurred in later stages. We propose that Ncx/Hox11L.1 is required for maintenance of proper functions of the enteric nervous system. These mutant mice can be used to elucidate a novel pathogenesis for human neuronal intestinal dysplasia. ( J. Clin. Invest. 1997. 100:795-801.)

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“…In almost all cases they have important roles in cellular differentiation and exhibit a characteristic ability of recognizing diverse DNA elements. Pit-1, for instance, is expressed exclusively in the anterior pituitary gland and is responsible for both the development of three of the five endocrine cell types and the tr^iis-activation of several genes, including prolactin (Prl) and growth hormone (GH) genes (Bodner et al 1988;Ingraham et al 1988;Li et al 1990;Lin et al 1992). Pit-1 binds to a complex pattern of sites within the promoters and enhancers of the genes it regulates.…”

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confidence: 99%

Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.

Jacobson¹,

Leon-Del-Rio²,

Rosenfeld³

et al. 1997

Genes Dev.

195

145

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Pit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical developmental functions based on binding to diverse DNA elements in its target genes. Here we report a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is accomplished by different spacing and orientation of the POU-specific domain. Contrary to previous predictions, the dimerization interface involves the carboxyl terminus of the DNA recognition helix of the homeodomain, which in an extended conformation interacts with specific residues at the amino terminus of helix al and in the loop between helices a3 and a4 of the POU-specific domain of the symmetry related monomer. These features suggest the molecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allostery between protein domains and DNA sites in the activation of target genes.[Key Words: Crystal structure; Pit-1; POU-domain factors; dimerization; spacing; orientation] Received October 25, 1996; revised version accepted December 3, 1996.The expression of specific genes in cells is often governed by families of transcription factors harboring DNA-binding motifs. In eukaryotes, these factors often exhibit extraordinary versatility. For instance, the bZip and helix-loop-helix families of transcription factors bind to DNA as both homo-and heterodimers (Bexevanis and Vinson 1993;Glover and Harrison 1995). The nuclear receptors go a step further and recognize DNA elements with different spacings and polarities between the half-sites (Naar et al. 1991;Umesono et al. 1991;Kurokawa et al. 1993). The POU domain family of transcription factors are perhaps the most remarkable in their ability to bind DNA as both monomers and dimers and in their ability to adopt diverse configurations (Wegner et al. 1993;Herr and Cleary 1995). Part of this versatility derives from their unusual bipartite structure, consisting of a highly conserved -75 amino acid POUspecific domain (POUg), tethered by a linker of variable length and composition, to a 60-amino-acid homeodomain (POUH). The flexibility of the linker, in particular, allows the possibility of different relative spacings and orientations between the subdomains. This helps to exThese authors contributed equally to this work. "Corresponding author. Present address:

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Pit-1-dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth

Cited by 311 publications

References 33 publications

Reversible Transdifferentiation: Interconversion of Somatotrophs and Lactotrophs in Pituitary Hyperplasia

Reversible Transdifferentiation: Interconversion of Somatotrophs and Lactotrophs in Pituitary Hyperplasia

A novel pathogenesis of megacolon in Ncx/Hox11L.1 deficient mice.

Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.

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