Molecular mechanisms for pituitary thyrotroph cell growth.
Neuroendocrine, endocrine and autocrine/paracrine signals contribute to the regulation of basal thyrotroph growth. Thyrotropin-releasing hormone (TRH), somatostatin, thyroid hormone (TH), estrogens (Es) and epidermal growth factor, all may play a role both in normal and tumoral thyrotroph proliferation, acting via either plasma membrane receptors and non-genomic steps or nuclear receptors and gene transcription. Signaling features common to all these ligands are involvement of G protein-coupled receptors, mitogen-activated protein kinase cascade and nuclear polyphosphoinositide cycle. In addition, each growth information, independently from the eliciting factor, may be routed intracellularly following a branched pathway, that often links different transduction systems at common check-points, as the Shc-Grb2-SOS complex. Finally, some ligands (e.g. TRH, TH, Es) may display opposite effects on thyrotroph growth, depending on environmental conditions and state of cell differentiation. These ambiguities of response can be interpreted using a "fuzzy" logic-based model of intracellular signaling. Accordingly, check-points common to different transduction cascades may be envisaged as targets for antitumoral therapy selective to the neoplastic thyrotroph cell.
Department of Human Anatomy, Universities of Parma, School of Medicine, Bologna, Italy.
A
A
Malaguti
C
C
Della Casa
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S
Castorina
A M
AM
Martelli
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E
Roti
E
E
Martino
R
R
Toni
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D010902:Pituitary Gland / Q000166:cytology / Q000254:growth & development*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013004:Somatostatin / Q000502:physiology; D013963:Thyroid Hormones / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology
D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D013963:Thyroid Hormones; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D011505:Protein-Tyrosine Kinases