Short-term effects of thyroid hormone in prenatal development and cell differentiation.
Extranuclear or nongenomic effects of thyroid hormones do not require interaction with the nuclear receptor, but are probably mediated by specific membrane receptors. This review will focus on the extranuclear effects of thyroid hormones on plasma membrane transport systems in non mammalian cells: chick embryo hepatocytes at two different stages of development, 14 and 19 days. At variance with mammals, the chick embryo develops in a closed compartment, beyond the influence of maternal endocrine factors. Thyroid hormones inhibit the Na+/K+-ATPase but stimulate the Na+/H+ exchanger and amino acid transport System A with different dose-responses: a bell-shaped curve in the case of the exchanger and a classic saturation curve in the case of System A. These effects are mimicked by the analog 3,5-diiodothyronine. Signal transduction is mediated by interplay among kinases, mainly protein kinase C and the MAPK pathway, initially primed by second messengers such as Ca2+, IP3, and DAG as in mammalian cells. Thyroid hormones and 3,5-diiodothyronine stimulate thymidine incorporation and DNA synthesis, associated with the increased levels and activity of cyclins and cyclin-dependent kinases involved in the G1/S transition, and also these effects have their starting point at the plasma membrane. Increasing evidence now demonstrates that thyroid hormones act as growth factors for chick embryo hepatocytes and their extranuclear effects are important for prenatal development and differentiation.
Incerpi
Sandra
S
Department of Biology, University of Rome Roma Tre, Viale Marconi 446, 00146 Rome, Italy. incerpi@uniroma3.it
Scapin
Sergio
S
D'Arezzo
Silvia
S
Spagnuolo
Silvana
S
Leoni
Silvia
S
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002642:Chick Embryo; D004104:Diiodothyronines / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development; D016193:G1 Phase; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D016196:S Phase; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013936:Thymidine / Q000737:chemistry; D013963:Thyroid Hormones / Q000378:metabolism*; D013997:Time Factors
D004104:Diiodothyronines; D017923:Sodium-Hydrogen Exchangers; D013963:Thyroid Hormones; C030103:3,5-diiodothyronine; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D013936:Thymidine