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Vol. 51. Núm. 7.
Páginas 405-417 (agosto 2004)
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Vol. 51. Núm. 7.
Páginas 405-417 (agosto 2004)
Acceso a texto completo
Lineas celulares adenohipofisarias αT3-1, LβT2, RC-4B/C y MtTW-10: regulacion y fisiologia celular
Anterior pituitary cell lines αt3-1, lβt2, rc-4b/c and mttw-10: regulation and cellular physiology
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M.C. Alonso-fuentes
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mcfuente@ull.es

Correspondencia: Dra. M.C. Alonso Fuentes. Laboratorio de Neurobiología Celular. Departamento de Fisiología. Facultad de Medicina. Universidad de La Laguna. 38071 La Laguna. Santa Cruz de Tenerife. España
, G. Hernández, R. Alonso
Laboratorio de Neurobiología Celular. Departamento de Fisiología. Instituto de Tecnologías Biomédicas. Universidad de La Laguna. La Laguna. Santa Cruz de Tenerife. España
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The anterior pituitary is a well-structured organ with a clearly defined function, which offers the possibility of studying the mechanisms involved in organogenesis and the maintenance of specific cell functions. Due to the cellular diversity of this endocrine gland, obtaining highly purified primary cell cultures from this organ is difficult. Recently developed techniques based on targeted oncogenesis have enabled immortalized cell lines that maintain specific differentiated phenotypes to be obtained and constitute a valuable tool for studying their cell biology. These model systems have allowed detailed investigation into cellular and molecular mechanisms otherwise inaccessible in vivo or in complex primary pituitary cell cultures. Thus, gonadotroph cell lines such as αT3-1 and LβT2 are representative of discrete stages of development that express differentiated functions of the gonadotroph lineage. In addition to these experimental systems, there are others that show a cellular population as diverse as those observed in adult anterior pituitary glands, such as the RC-4B/C and MtTW-10 cell lines. In the present article we provide a brief description of each of the above-mentioned cell lines and review several aspects of their regulation by various factors.

Key words:
Cell lines
Oncogenesis
Pituitary gland
Gonadotrophs
Differentiation
GnRH
Luteinizing hormone
Follicle-stimulating hormone

La adenohipófisis es un órgano bien estructurado y con una función claramente definida, que ofrece la posibilidad de estudiar los mecanismos que intervienen en la organogenia y el mantenimiento de funciones celulares específicas. Debido a la gran diversidad celular de esta glándula endocrina, la obtención de cultivos primarios altamente purificados de tipos celulares concretos a partir de este órgano es una tarea difícil. El desarrollo reciente de técnicas de oncogenia dirigida ha permitido la obtención de líneas celulares que mantienen fenotipos diferenciados específicos y que son una herramienta valiosa para el estudio de su biología celular. Estos sistemas permiten la investigación detallada de mecanismos celulares y moleculares que, de otra manera, resultarían difícilmente accesibles tanto in vivo como en cultivos primarios de células adenohipofisarias. De esta forma, líneas celulares, como αT3-1 y LβT2, representan estadios discretos del desarrollo y se caracterizan básicamente por la expresión de funciones diferenciadas del linaje de células gonadotropas. Junto con estos sistemas experimentales existen otros que muestran una población celular tan diversa como la observada en glándulas adenohipofisarias adultas, como ocurre en las líneas celulares RC-4B/C y MtTW-10. En este artículo presentamos una descripción resumida de cada una de las líneas mencionadas anteriormente, y revisamos varios aspectos acerca de su regulación por diferentes factores.

Palabras clave:
Líneas celulares
Oncogenia
Adenohipófisis
Células gonadotropas
Diferenciación
GnRH
Hormona luteinizante
Hormona foliculoestimulante
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Bibliografía
[1.]
J.J. Windle, R.I. Weiner, P.L. Mellon.
Cell lines of the pituitary gonadotrope lineage derived by targeted oncogenesis in transgenic mice.
Mol Endocrinol, 4 (1990), pp. 597-603
[2.]
P.M. Dubois, A. El Amraoui, A.G. Heritier.
Development and differentiation of pituitary cells.
[3.]
K.M. Scully, M.G. Rosenfeld.
Pituitary development: regulatory codes in mammalian organogenesis.
Science, 295 (2002), pp. 2231-2235
[4.]
M.A. Japon, M. Rubinstein, M.J. Low.
In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development.
J Histochem Cytochem, 42 (1994), pp. 1117-1125
[5.]
E.T. Alarid, S. Holley, M. Hayakawa, P.L. Mellon.
Discrete stages of anterior pituitary differentiation recapitulated in immortalized cell lines.
Mol Cel Endocrinol, 140 (1998), pp. 25-30
[6.]
E.T. Alarid, J.J. Windle, D.B. Whyte, P.L. Mellon.
Immortalization of pituitary cells at discrete stages of development by directed oncogenesis in transgenic mice.
Development, 122 (1996), pp. 3319-3329
[7.]
U.B. Kaiser, P.M. Conn, W.W. Chin.
Studies of gonadotropin-releasing hormone (GnRH) action using GnRH receptor-expressing pituitary cell lines.
Endocr Rev, 18 (1997), pp. 46-70
[8.]
I. Nakayama, P.A. Nickerson.
Suppression of anterior pituitary in rats bearing a transplantable growth hormone and prolactinsecreting tumor (MtT-W10).
Endocrinology, 92 (1973), pp. 516-524
[9.]
I. Hurbain-Kosmath, A. Berault, N. Noel, J. Polkowska, A. Bohin, M. Jutisz, et al.
Gonadotropes in a novel rat pituitary tumor cell line, RC-4B/C. Establishment and partial characterization of the cell line.
In Vitro Cell Dev Biol, 26 (1990), pp. 431-440
[10.]
R. Sosnowski, P.L. Mellon, M.A. Lawson.
Activation of translation in pituitary gonadotrope cells by gonadotropin-releasing hormone.
Mol Endocrinol, 14 (2000), pp. 1811-1819
[11.]
S. Kraus, Z. Naor, R. Seger.
Intracellular signaling pathways mediated by the gonadotropin-releasing hormone (GnRH) receptor.
Arch Med Res, 32 (2001), pp. 499-509
[12.]
M.S. Johnson, D.J. MacEwan, J. Simpson, R. Mitchell.
Characterization of protein kinase C isoforms and enzymatic activity from the αT3-1 gonadotroph-derived cell line.
FEBS, 333 (1993), pp. 67-72
[13.]
F. Merelli, S.S. Stojilkovia, T. Iida, L.Z. Krsmanovic, L. Zheng, P.L. Mellon, et al.
Gonadotropin-releasing hormone-induced calcium signaling in clonal pituitary gonadotrophs.
Endocrinology, 131 (1992), pp. 925-932
[14.]
C.A. McArdle, W. Forrest-Owen, G. Willars, J. Davidson, A. Poch, M. Kratzmeier.
Desensitization of gonadotropin-releasing hormone action in the gonadotrope-derived αT3-1 cell line.
Endocrinology, 136 (1995), pp. 4864-4871
[15.]
C.A. McArdle, W. Forrest-Owen.
Pituitary adenylate cyclase-activating polypeptide (PACAP) actions on αT3-1 gonadotrophs show desensitization.
J Neuroendocrinol, 9 (1997), pp. 893-901
[16.]
B. Junoy, H. Maccario, J. Mas, A. Enjalbert, S.V. Drouva.
Proteasome implication in phorbol ester. and GnRH-induced selective down-regulation of PKC (α, ε, Ä) in αT3-1 and LÀT2 gonadotropes cell lines.
Endocrinology, 143 (2002), pp. 1386-1403
[17.]
M. Hezareh, W. Schlegel, S.R. Rawlings.
Stimulation of Ca2+ influx in αT3-1 gonadotrophs via the cAMP/PKA signaling system.
Am J Physiol, 273 (1997), pp. E850-E858
[18.]
E. Schomerus, A. Poch, R. Bunting, W.T. Mason, C.A. McArdle.
Effects of Pituitary Adenylate Cyclase-Activating Polypeptide in the pituitary: activation of two signal transduction pathways in the gonadotrope-derived αT3-1 cell line.
Endocrinology, 134 (1994), pp. 315-323
[19.]
C.A. McArdle, E. Schomerus, I. Groner, A. Poch.
Estradiol regulates gonadotropin-releasing hormone receptor number, growth and inositol phosphate production in αT3-1 cells.
Mol Cell Endocrinol, 87 (1992), pp. 95-103
[20.]
B. Williams, A.N. Brooks, T.C. Aldrige, W.D. Pennie, R. Stephenson, C.A. McArdle.
Oestradiol is a potent mitogen and modulator of GnRH signalling in αT3-1 cells: are these effects causally related?.
J Endocrinol, 164 (2000), pp. 31-43
[21.]
D.A. Shreihofer, E.M. Resnick, V. Lin, M.A. Shupnick.
Ligand-independent activation of pituitary ER: Dependence on PKA-stimulated pathways.
Endocrinology, 142 (2001), pp. 3361-3368
[22.]
O. Ortmann, M. Bakhit, P. Bloh, K-D Schulz, G. Emons.
Ovarian steroids modulate gonadotropin-releasing hormone-induced biphasic luteinizing hormone secretory responses and inositol phosphate accumulation in rat anterior pituitary cells and αT3-1 gonadotrophs.
J Steroid Biochem Molec Biol, 54 (1995), pp. 101-109
[23.]
S.V. Drouva, I. Gorenne, E. Laplante, E. Rerat, A. Enjalbert, C. Kordon.
Estradiol modulates Protein Kinase C activity in the rat pituitary in vivo and in vitro.
Endocrinology, 126 (1990), pp. 536-544
[24.]
C.A. McArdle, W. Forrest-Owen, J.S. Davidson, R. Fowkes, R. Bunting, W.T. Mason, et al.
Ca2+ entry in gonadotrophs and αT3-1 cells: does store-dependent Ca2+ influx mediate gonadotrophin-releasing hormone action?.
J Endocrinol, 149 (1996), pp. 155-169
[25.]
M.M. Bosma, B. Hille.
Electrophysiological properties of a cell line of the gonadotrope lineage.
Endocrinology, 130 (1992), pp. 3411-3420
[26.]
N.L. Levi, T. Hanoch, O. Benard, M. Rozenblat, D. Harris, N. Reiss, et al.
Stimulation of Jun N-terminal Kinase (JNK) by gonadotropin-releasing hormone in pituitary αT3-1 cell line is mediated by protein kinase C, c-Src, and CDC42.
Mol Endocrinol, 12 (1998), pp. 815-824
[27.]
Z. Naor, O. Bernard, R. Seger.
Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor.
TEM, 11 (2000), pp. 91-99
[28.]
M.S. Johnson, E.M. Lutz, C.J. MacKenzie, W.B. Wolbers, D.N. Robertson, P.J. Holland, et al.
Gonadotropin-releasing hormone receptor activation of extracellular signal-regulated kinase and tyrosine kinases in transfected GH3 cells and in αT3-1 cells.
Endocrinology, 141 (2000), pp. 3087-3097
[29.]
J.L. Turgeon, Y. Kimura, D.W. Waring, P.L. Mellon.
Steroid and pulsatile gonadotropin releasing hormone (GnH) regulation of luteinizing hormone and GnRH receptor in a novel gonadotrope cell line.
Mol Endocrinol, 10 (1996), pp. 439-450
[30.]
D.A. Schreihofer, M.H. Stoler, M.A. Shupnik.
Differential expresion and regulation of Estrogen Receptors (ERs) in rat pituitary and cell lines: Estrogen decreases ERα protein and estrogen responsiveness.
Endocrinology, 141 (2000), pp. 2174-2183
[31.]
K.E. Graham, K.D. Nusser, M.J. Low.
LβT2 gonadotroph cells secrete follicle stimulating hormone (FSH) in response to activin.
A J Endocrinol, 162 (1999), pp. R1-R5
[32.]
F. Pernasetti, V.V. Vasilyev, S.B. Rosenberg, J.S. Bailey, H. Huang, W.L. Miller, et al.
Cell-specific transcriptional regulation of follicle-stimulating hormone-β by activin and gonadotropin-releasing hormone in the LβT2 pituitary gonadotrope cell model.
Endocrinology, 142 (2001), pp. 2284-2294
[33.]
M.A. Lawson, D. Li, C.A. Glidewell-Kenney, F.J. Lopez.
Androgen responsiveness of the pituitary gonadotrope cell line LβT2.
J Endocrinol, 170 (2001), pp. 601-607
[34.]
F. Liu, D.A. Austin, P.L. Mellon, J.M. Olefsky.
Webster NJG.
GnRH activates ERK1/2 leading to the Induction of c-fos and LHβ protein expression in LβT2 Mol Cell Endocrinol, 16 (2002), pp. 419-434
[35.]
T. Yokoi, M. Ohmichi, K. Tasaka, A. Kimura, Y. Kanda, J. Hayakawa, et al.
Activation of the luteinizing hormone β promoter by gonadotropin-releasing hormone requires c-Jun NH2-terminal protein kinase.
J Biol Chem, 275 (2000), pp. 21639-21647
[36.]
P. Thomas, P.L. Mellon, J.L. Turgeon, D.W. Waring.
The LβT2 clonal gonadotrope: a model for single cell studies of endocrine cell secretion.
Endocrinology, 137 (1996), pp. 2979-2989
[37.]
Y. Fujii, Y. Okada, J.P. Moore, A.C. Dalkin, S.J. Winters.
Evidence that PACAP and GnRH down-regulates follicle-stimulating hormone-β mRNA levels by stimulating follistatin gene expression: effects on folliculostellate cells, gonadotrophs and LβT2 gonadotroph cells.
Mol Cell Endocrinol, 192 (2002), pp. 55-64
[38.]
L. Chen, T. Sakai, S. Sakamoto, M. Kato, K. Inoue.
Direct evidence of ganadotropin-releasing hormone (GnRH)-stimulated nitric oxide production in the LβT2 clonal gonadotropes.
Pituitary, 2 (1999), pp. 191-196
[39.]
F. Pernasetti, V.V. Vasilyev, S.B. Rosenberg, et al.
Cell-specific transcriptional regulation of follicle-stimulating hormone-β by activin and gonadotropin-releasing hormone in the LβT2 pituitary gonadotrope cell model.
Endocrinology, 142 (2001), pp. 2284-2295
[40.]
J. Polkowska, A. Berault, I. Hurbain-Kosmath, G. Jolly, M. Jutisz.
Bihormonal cells producing gonadotropins and prolactin in a rat pituitary tumor cell line (RC-4B/C).
Neuroendocrinology, 54 (1991), pp. 267-273
[41.]
J.F. Hyde, A. Cai, J.P. Moore.
Characterization of a pituitary cell line producing the peptide galanin.
Soc Neurosci, 22 (1996), pp. 1591
[42.]
J. Trouillas, P. Chevalier, C. Remy, F. Rajas, R. Cohen, A. Calle, et al.
Differential actions of the dopamine agonist bromocriptine on growth of SMtTW tumors exhibiting a prolactin and/or a somatotroph cell phenotype: relation to dopamine D2 receptor expression.
Endocrinology, 140 (1999), pp. 13-21
[43.]
J.F. Hyde, D.G. Morrison, J.P. Moore, G. Howard.
MtTW-10 pituitary tumor cells: galanin gene expression and peptide secretion.
Endocrinology, 133 (1993), pp. 2588-2593
[44.]
G. Howard, L. Peng, J.F. Hyde.
An estrogen receptor binding site within the human galanin gene.
Endocrinology, 138 (1997), pp. 4649-4656
[45.]
J.J. Evans.
Modulation of gonadotropin levels by peptides acting at the anterior pituitary gland.
Endoc Rev, 20 (1999), pp. 46-67
[46.]
L. Anderson.
Intracellular mechanisms triggering gonadotrophin secretion.
Rev Reprod, 1 (1996), pp. 193-202
[47.]
O. Ortmann, K. Diedrich.
Pituitary and extrapituitary actions of gonadotrophin-releasing hormone and its analogues.
Hum Reprod, 14 (1999), pp. 194-206
[48.]
L.Z. Krsmanovic, A.J. Martinez-Fuentes, K.K. Arora, N. Mores, M. Tomic, S.S. Stojilkovic, et al.
Local regulation of gonadotroph function by pituitary gonadotropin-releasing hormone.
Endocrinology, 141 (2000), pp. 1187-1195
[49.]
S.S. Stojilkovic, K.J. Catt.
Calcium oscillations in anterior pituitary cells.
Endocr Rev, 13 (1992), pp. 256-280
[50.]
H. Lewy, I.E. Ashkenazi, Z. Naor.
Gonadotropin releasing hormone (GnRH) and estradiol (E2) regulation of cell cycle in gonadotrophs.
Mol Cell Endocrinol, 203 (2003), pp. 25-32
[51.]
C. Trueta, M. Diaz, L.A. Vaca, C. Clapp, G. Martinez de la Escalera.
Functional uncoupling between intracellular calcium dynamics and secretion in the αT3-1 gonadotropic cell line.
[52.]
J. Schwartz.
Intercellular comunication in the anterior pituitary.
Endocr Rev, 21 (2000), pp. 488-513
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