Información del artículo
Las ratas Zucker, descritas por primera vez en 1961, constituyen una cepa con patología múltiple que incluye obesidad, infertilidad, resistencia insulínica, disminución del gasto energético y múltiples alteraciones neuroendocrinas. La causa originaria de esta patología es una mutación en el gen de la leptina, que induce alteraciones neuroendocrinas variadas. En la presente revisión se analizan las características de la función del eje hipotálamo/hipófisis/gónadas, con especial énfasis en la etiopatogenia de las alteraciones observadas y los ensayos de terapia génica desarrollados. También se analizan las alteraciones en la conducta reproductora y las incógnitas que el modelo plantea en la actualidad.
Palabras clave:
Zucker
Hipotálamo
Hipófisis
Gónadas
The Zucker rat, a strain first described in 1961, shows multiple pathological alterations, such as obesity, infertility, insulin resistance, reduced energy expenditure, and multiple neuroendocrine alterations. The initial genetic failure of this strain is a leptin receptor missense mutation. In the present review, we analyze the characteristics of hypothalamic-pituitary-gonadal axis function, with special emphasis on the mechanisms of action involved in the different neuroendocrine alterations and on gene therapy approaches. Alterations in reproductive function and the possible future areas of interest in this field are also discussed.
Key words:
Zucker
Hypothalamus
Pituitary gland
Gonads
El Texto completo está disponible en PDF
Bibliografía
[1.]
L.M. Zucker, T.F. Zucker.
Fatty, a new mutation in the rat.
J Hered, 52 (1961), pp. 275-278
[2.]
L.M. Zucker.
Hereditary obesity in the rat associated with hyperlipemia.
Ann N Y Acad Sci, 131 (1965), pp. 447-458
[3.]
J.M. Argiles.
The obese Zucker rat: a choice for fat metabolism 1968-1988 twenty years of research on the insights of Zucker mutation.
Prog Lipid Res, 28 (1989), pp. 53-66
[4.]
B.L. Kasiske, M.P. O’Donnell, W.F. Keane.
The Zucker rat model of obesity, insulin resistance, hyperlipidemia, and renal injury.
Hypertension, 19 (1992), pp. 1110-1115
[5.]
B.J. Plotkin, D. Paulson.
Zucker rat (fa/fa), a model for the study of immune function in II diabetes mellitus: effect of exercise and caloric restriction on phagocytic activity of macrophages.
Lab Anim Sci, 46 (1996), pp. 682-684
[6.]
I. Ahmad, A.W. Steegles, A.J. Carrillo, J.A. Finkelstein.
Obesityand sex-related alterations in growth hormone messenger RNA levels.
Mol Cell Endocrinol, 65 (1989), pp. 103-109
[7.]
J.W. Leidy Jr, T.M. Romano, W.J. Millard.
Developmental and sex-related changes of the growth hormone axis in lean and obese Zucker rats.
Neuroendocrinology, 57I 2 (1993), pp. 213-223
[8.]
J.A. Finkelstein, P. Jervois, M. Menadue, J.O. Willoughby.
Growth hormone and prolactin secretion in genetically obese rats.
Endocrinology, 118 (1986), pp. 1233-1236
[9.]
I. Ahmad, J.A. Finkelstein, T.R. Downs, L.A. Frohman.
Obesityassociated decrease in growth hormone-releasing hormone gene expression: a mechanism for reduced growth hormone mRNA levels in genetically obese Zucker rats.
Neuroendocrinology, 58 (1993), pp. 332-337
[10.]
G.S. Tannenbaum, J. Epelbaum, C. Videau, J.M. Dubuis.
Sex-related alterations in hypothalamic growth hormone-releasing hormone mRNA-but not somatostatin mRNA-expressing cells in genetically obese Zucker rats.
Neuroendocrinology, 64 (1996), pp. 186-193
[11.]
G. Renier, P. Gaudreau, N. Deslauriers, P. Brazeau.
In vitro and in vivo growth hormone responsiveness to growth hormone-releasing factor in male and female Zucker rats.
Neuroendocrinology, 50 (1989), pp. 454-459
[12.]
G. Renier, P. Gaudreau, N. Deslauriers, D. Petitclerc, P. Brazeau.
Dynamic of the GRF-induced GH response in genetically obese Zucker rats: influence of central and peripheral factors.
Mol Cell Endocrinol, 65 (1989), pp. 103-109
[13.]
S. Saiduddin, G.A. Bray, D.A. York, R.S. Swerdloff.
Reproductive function in the genetically obese “fatty” rat.
Endocrinology, 93 (1973), pp. 1251-1256
[14.]
M. Tena-Sempere, M.L. Barreiro.
Leptin in male reproduction: the testis paradigm.
Mol Cell Endocrinol, 188 (2002), pp. 9-13
[15.]
M.L. Barreiro, M. Tena-Sempere.
Ghrelin and reproduction: a novel signal linking energy status and fertility.
Mol Cell Endocrinol, 226 (2004), pp. 1-9
[16.]
M. Korbonits, A.P. Goldstone, M. Gueorguiev, A.B. Grossman.
Ghrelin, a hormone with multiple functions.
Front Neuroendocrinol, 25 (2004), pp. 27-68
[17.]
C.L. Marin Bives, D.H. Olster.
Abnormal estrous ciclicity and behavioral hyporesponsiveness to ovarian hormones in genetically obese Zucker female rats.
Endocrinology, 138 (1997), pp. 143-148
[18.]
E.K. Rhinehart, S.P. Kalra, P.S. Kalra.
Leptin-receptor gene transfer into the arcuate nucleus of female fatty Zucker rats using recombinant adeno-associated viral vectors stimulates the hypothalamo-pituitary-gonadal axis.
Biol Reprod, 71 (2004), pp. 266-272
[19.]
B.J. Todd, S.R. Ladyman, D.R. Grattan.
Suppression of pulsatile luteinizing hormone secretion but not of luteinizing hormone surge in leptin resistant obese Zucker rat.
J Neuroendocrinol, 15 (2003), pp. 61-68
[20.]
L.A. Pawekczyk, Y.S. Moon, B.H. Yuen.
Ovulatory response, ovarian LH/hCG receptors and serum concentrations of LH, insulin and steroid hormones in immature Zucker rats after PMSG treatment.
Anim Reprod Sci, 32 (1999), pp. 135-146
[21.]
A.M. Chelich, E.S. Edmonds.
Pseudopregnancy and decidual response in the obese Zucker rat: a re-examination.
Biol Reprod, 34 (1986), pp. 805-808
[22.]
H.L. Heiman, J.R. Porter, M.V. Nekola, W.A. Murphy, A.D. Hartman, V.A. Lance, et al.
Adenohypophyseal response to hypophysiotropic hormones in male obese Zucker rats.
Am J Physiol, 249 (1985), pp. E380-E384
[23.]
E.M. Whitaker, A.C. Robinson.
Circulating reproductive hormones and hypothalamic oestradiol and progestin receptors in infertile Zucker rats.
J Endocrinol, 120 (1989), pp. 331-336
[24.]
E. Carro, L. Pinilla, L.M. Seoane, R.V. Considine, E. Aguilar, F.F. Casanueva, et al.
Influence of endogenous leptin tone on the estrous cycle and luteinizing hormone pulsatility in female rats.
Neuroendocrinology, 66 (1997), pp. 375-376
[25.]
M.C. Lebrethon, E. Vandermissen, A. Gerard, A.S. Parent, J.P. Bourguignon.
Cocaine and amphetamine-regulated-transcript peptide mediation of leptin stimulatory effect on the rat gonadotropin- releasing hormone pulse generator in vitro.
J Neuroendocrinol, 12 (2000), pp. 383-385
[26.]
S.K. Gale, T.B. Van Itallie.
Genetic obesity: estrogenic influences on the body weight and food intake of lean and obese adult Zucker (fa/fa) rats.
Physiol Behav, 23 (1979), pp. 111-120
[27.]
S. Saiduddin, G.A. Bray, D.A. York, R.S. Swerdloff.
Reproductive function in the genetically obese “fatty” rat.
Endocrinology, 93 (1973), pp. 1251-1256
[28.]
R.A. Young, R. Frink, C. Longcope.
Serum testosterone and gonadotropin in the genetically obese male Zucker rat.
Endocrinology, 111 (1982), pp. 977-981
[29.]
E.M. Whitaker, M.A. Shaw, G.R. Hervey.
Plasma oestradiol-17 beta and testosterone concentrations as possible causes of the infertility of congenitally obese Zucker rats.
J Endocrinol, 99 (1983), pp. 485-490
[30.]
B. Withyachumnarnkul, E.S. Edmonds.
Plasma testosterone levels and sexual performance of young obese male Zucker rats.
Physiol Behav, 29 (1982), pp. 773-777
[31.]
J.K. Young, M.W. Fleming, D.E. Matsumoto.
Sex behavior and the sexually dimorphic hypothalamic nucleus in male Zucker rats.
Physiol Behav, 36 (1986), pp. 881-886
[32.]
B. Beck, J.P. Max, S. Richy, A. Stricker-Krongrad.
Feeding response to a potent-releasing peptide agonist in lean and obese Zucker rats.
Brain Res, 1016 (2004), pp. 135-138
[33.]
T.L. Powley, S.A. Morton.
Hypophysectomy and regulation of body weight in the genetically obese Zucker rat.
Am J Physiol, 230 (1976), pp. 982-987
[34.]
C.L. Marin Bivens, D.H. Olster.
Opioid receptor blockade promotes weight loss and improves the display of sexual behaviors in obese Zucker female rats.
Pharmacol Biochem Behav, 63 (1999), pp. 515-520
[35.]
J.D. Balustein, D.H. Olster.
Gonadal steroid hormone receptors and social behaviors.
pp. 31-104
[36.]
D.H. Olster, I.D. Auerbach.
Deficits in progesterone-facilitated sexual behaviors and forebrain estrogen and progestin receptors in obese female Zucker rats.
Neuroendocrinology, 72 (2000), pp. 350-359
[37.]
R.B. Hemmes, R. Schoch.
High dosage testosterone propionate induces copulatory behavior in the obese male Zucker rat.
Physiol Behav, 43 (1988), pp. 321-324
[38.]
M.S. Philips, Q. Liu, H.A. Hammond, V. Dugand, P.J. Hey, C.J. Caskey, et al.
Leptin receptor missense mutation in the fatty Zucker rat.
Nature Genetics, 13 (1996), pp. 18-19
[39.]
F.F. Casanueva, C. Diéguez.
Neuroendocrine regulation and actions of leptin.
Front Neuroendocrinol, 20 (1999), pp. 317-363
[40.]
M. Tena-Sempere, M.L. Barreiro.
Leptin in male reproduction: the testis paradigm.
Mol Cell Endocrinol, 188 (2002), pp. 9-13
[41.]
S. Nagatani, Y. Zeng, D.H. Keisler, D.L. Foster, C.A. Jaffe.
Leptin regulates pulsatile luteinizing hormone and growth hormone secretion in the sheep.
Endocrinology, 141 (2000), pp. 3965-3975
[42.]
S. Nagatani, P. Guthikonda, R.C. Thompson, H. Tsukamura, K.I. Maeda, D.L. Foster.
Evidence for GnRH regulation by leptin: leptin administration prevents reduced pulsatile LH secretion during fasting.
Neuroendocrinology, 67 (1998), pp. 370-376
[43.]
P.D. Finn, M.J. Cunningham, K.Y. Pau, H.G. Spies, D.K. Clifton, R.A. Steiner.
The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey.
Endocrinology, 139 (1998), pp. 4652-4662
[44.]
W.H. Yu, M. Kimura, A. Walczewska, S. Karanth, S.M. McCann.
Role of leptin in hypothalamic-pituitary function.
Proc Natl Acad Sci, 94 (1997), pp. 1023-1028
[45.]
W.H. Yu, A. Walczewska, S. Karanth, S.M. McCann.
Nitric oxide mediates leptin-induced luteinizing hormone-releasing hormone (LHRH) and leptin-induced LH release from the pituitary gland.
Endocrinology, 138 (1997), pp. 5055-5058
[46.]
M.J. Cunningham, D.K. Clifton, R.A. Steiner.
Leptin's actions on the reproductive axis: perspectives and mechanism of action.
Biol Reprod, 60 (1999), pp. 216-222
[47.]
P. Magni, R. Vettor, C. Pagano, A. Calcagno, E. Beretta, E. Messi, et al.
Expression of a leptin receptor in immortalized gonadotropin- releasing hormone-secreting neurons.
Endocrinology, 140 (1999), pp. 1581-1585
[48.]
M. Tena-Sempere, L. Pinilla, L.C. González, J. Navarro, C. Diéguez, F.F. Casanueva, et al.
In vitro pituitary and testicular effects of the leptin-related synthetic peptide leptin (116-130) amide involve actions both similar to and distinct from those of the native leptin molecule in the adult rat.
Eur J Endocrinol, 142 (2000), pp. 406-410
[49.]
J.T. Clark, P.S. Kalra, S.P. Kalra.
Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats.
Endocrinology, 117 (1985), pp. 2435-2442
[50.]
S.P. Kalra, M.G. Dube, S. Pu, B. Xu, T.L. Horvath, P.S. Kalra.
Interacting appetite-regulating pathways in the hypothalamic regulation of body weight.
Endocr Rev, 20 (1999), pp. 68-100
[51.]
L.G. Allen, P.S. Kalra, W.R. Crowley, S.P. Kalra.
Comparison of the effects of neuropeptide Y and adrenergic transmitters on LH release and food intake in male rats.
Life Sci, 37 (1985), pp. 617-623
[52.]
P.S. Kalra, S.P. Kalra.
Steroidal modulation of the regulatory neuropeptides: luteinizing hormone releasing hormone, neuropeptide Y, and endogenous opioid peptides.
J Steroid Biochem, 25 (1986), pp. 733-740
[53.]
S.P. Kalra, P.S. Kalra, A. Sahu, L.G. Allen, W.R. Crowley.
The steroid-neuropeptide connection in the control of LHRH secretion.
Adv Exp Med Biol, 219 (1987), pp. 65-83
[54.]
O. Khorram, K.Y. Pau, H.G. Spies.
Bimodal effects of neuropeptide Y on hypothalamic release of gonadotropin-releasing hormone in conscious rabbits.
Neuroendocrinology, 45 (1987), pp. 290-297
[55.]
S.P. Kalra, P.S. Kalra.
Nutritional infertility: the role of the interconnected hypothalamic neuropeptide Y-galanin-opioid network.
Front Neuroendocrinol, 17 (1996), pp. 371-401
[56.]
T.L. Horvath, F. Naftolin, S.P. Kalra, C. Leranth.
Neuropeptide-Y innervation of ß-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis.
Endocrinology, 131 (1991), pp. 2461-2467
[57.]
B.V. Beck, A. Burlet, J.P. Nicolas, C. Burlet.
Hypothalamic neuropeptide Y (NPY) in obese Zucker rats: implications in feeding and sexual behaviors.
Physiol Behav, 47 (1990), pp. 449-453
[58.]
P.E. McKibbin, S.J. Cotton, S. McMillan, B. Holloway, R. Mayers, H.D. McCarthy, et al.
Altered neuropeptide Y concentrations in specific hypothalamic regions of obese (fa/fa) Zucker rats. Possible relationship to obesity and neuroendocrine disturbances.
Diabetes, 40 (1991), pp. 1423-1429
[59.]
T.J. Kowalski, A.M. Ster, G.P. Sdmith.
Ontogeny of hyperphagia in the Zucker (fa/fa) rat.
Am J Physiol, 275 (1998), pp. R1106-R1109
[60.]
T.J. Kowalski, T.A. Houpt, J. Jahng, N. Okada, S.M. Liu, S.C. Chua Jr, et al.
Neuropeptide Y overexpression in the prewanling Zucker (fa/fa) rat.
Physiol Behav, 47 (1990), pp. 449-453
[61.]
G. Sanacora, M. Kershaw, J.A. Finkelstein, J.D. White.
Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation.
Endocrinology, 127 (1990), pp. 730-737
[62.]
C. Catzeflis, D.D. Pierroz, F. Rohner-Jeanrenaud, J.E. Rivier, P. Sizonenko, M.L. Aubert.
Neuropeptide Y administered chronically into the lateral ventricle profoundly inhibits both the gonadotropic and somatotropic axis in intact adult female rats.
Endocrinology, 133 (1993), pp. 224-234
[63.]
N. Pronchuk, W.F. Colmers.
NPY presynaptic actions are reduced in the hypothalamic mpPVN of obese (fa/fa), but not lean, Zucker rats in vitro.
Br J Pharmacol, 141 (2004), pp. 1032-1036
[64.]
P.S. Kalra, M. Norlin, S.P. Kalra.
Neuropeptide Y stimulates betaendorphin release in the basal hypothalamus: role of gonadal steroids.
Brain Res, 705 (1995), pp. 353-356
[65.]
A. Sahu, W.R. Crowley, S.P. Kalra.
An opioid-neuropeptide-Y transmission line to luteinizing hormone (LH)-releasing hormone neurons. A role in the induction of LH surge.
Endocrinology, 126 (1990), pp. 876-883
[66.]
J.A. Thornhill, B. Taylor, W. Marshall, K. Parent.
Central, as well as peripheral naloxone administration supresses feeding in food-deprived Sprague-Dawley and genetically obese (Zucker) rats.
Physiol Behav, 29 (1982), pp. 841-846
[67.]
C.L. McLaughlin, C.A. Baile.
Nalmefene decreases meal size, food and water intake and weight gain in Zucker rats.
Pharmacol Biochem Behav, 19 (1983), pp. 235-240
[68.]
C.L. McLaughlin, C.A. Baile.
Feeding behavior responses of Zucker rats to naloxone.
Physiol Behav, 32 (1984), pp. 755-761
[69.]
W.N. Shaw.
Long-term treatment of obese Zucker rats with LY255582 and other appetite suppressants.
Pharmacol Biochem Behav, 46 (1993), pp. 653-659
[70.]
S. Funes, J.A. Hendrick, G. Vassileva, L. Markowitz, S. Abbondanzo, A. Golovko, et al.
The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system.
Biochem Biophys Res Commun, 312 (2003), pp. 1357-1363
[71.]
S.B. Seminara, S. Messager, E.E. Chatzidaki, R.R. Thresher, J.S. Acierno Jr, J.K. Shagoury, et al.
2003 The GPR54 gene as a regulatorof puberty.
N Engl J Med, 349 (2003), pp. 1614-2772
[72.]
D.K. Lee, T. Nguyen, G.P. O’Neill, R. Cheng, Y. Liu, A.D. Howard, et al.
Discovery of a receptor related to the galanin receptors.
FEBS Lett, 446 (1999), pp. 103-107
[73.]
T. Ohtaki, Y. Shintani, S. Honda, H. Matsumoto, A. Hori, K. Kanehashi, et al.
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G protein-coupled receptor.
Nature, 411 (2001), pp. 613-617
[74.]
A.I. Muir, L. Chamberlain, N.A. Elshourbagy, D. Michalovich, D.J. Moore, A. Calamari, et al.
AXOR12, a novel human G protein- coupled receptor, activated by the peptide KiSS-1.
J Biol Chem, 276 (2001), pp. 28969-28975
[75.]
M. Kotani, M. Detheux, A. Vandenbogaerde, D. Communi, J.M. Vanderwinden, E. Le Poul, et al.
The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54.
J Biol Chem, 276 (2001), pp. 34631-34636
[76.]
M. Bilban, N. Ghaffari-Tabrizi, E. Hihtermann, S. Bauer, S. Molzer, C. Zoratti, et al.
Kisspeptin-10, a KiSS-1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts.
J Cell Sci, 117 (2004), pp. 1319-1328
[77.]
V.M. Navarro, J.M. Castellano, R. Fernández Fernández, M.L. Barreiro, J. Roa, J.E. Sánchez Criado, et al.
Developmental and hormonally regulated messenger RNA expression of KiSS-1 and its putative receptor GPR54 in rat hypothalamus and potent gonadotropin releasing action of KiSS-1 peptide.
Endocrinology, 145 (2004), pp. 456-474
[78.]
V.M. Navarro, J.M. Castellano, R. Fernández-Fernández, S. Tovar, J. Roa, A. Mayén, et al.
Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54.
Endocrinology, 146 (2005), pp. 156-163
[79.]
V.M. Navarro, J.M. Castellano, R. Fernández-Fernández, S. Tovar, J. Roa, A. Mayén, et al.
Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat.
Endocrinology, 146 (2005), pp. 1686-1688
[80.]
R. Fernández-Fernández, V.M. Navarro, M.L. Barreiro, E.M. Vigo, S. Tovar, A.V. Sirotkin, et al.
Effects of chronic hyperghrelinemia on puberty onset and pregnancy outcome in the rat.
Endocrinology, 146 (2005), pp. 3018-3025
[81.]
V.M. Navarro, R. Fernández Fernández, J.M. Castellano, J. Roa, A. Mayén, M.L. Barreiro, et al.
Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54.
J Physiol, 561 (2004), pp. 379-386
[82.]
J.M. Castellano, V.M. Navarro, R. Fernández-Fernández, R. Nogueiras, S. Tovar, J. Roa, et al.
Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by Kisspeptin in undernutrition.
Endocrinology, 146 (2005), pp. 3917-3925
[83.]
T. Ohtaki, S. Kumano, Y. Ishibashi, K. Ogi, H. Matsui, M. Harada, et al.
Isolation and cDNA cloning of a novel galanin-like peptide (GALP) from porcine hypothalamus.
J Biol Chem, 274 (1999), pp. 37041-37045
[84.]
J.A. Larm, A.L. Gundlach.
Galanin-like peptide (GALP) Mrna expression is restricted to arcuate nucleus of hypothalamus in adult male rat brain.
Neuroendocrinology, 72 (2000), pp. 67-71
[85.]
N.C. Kerr, F.E. Colmes, D. Wynick.
Galanin-like peptide (GALP) is expressed in rat hypothalamus and pituitary, but not in DRG.
Neuroreport, 11 (2000), pp. 3909-3913
[86.]
Y. Takatsu, H. Matsumoto, T. Ohtaki, S. Kumano, C. Kitada, H. Onda, et al.
Distribution of galanin-like peptide in the rat brain.
Endocrinology, 142 (2001), pp. 1626-1634
[87.]
H. Matsumoto, J. Noguchi, Y. Takatsu, Y. Horikoshi, S. Kumano, T. Ohtaki, et al.
Stimulation effect of galanin-like peptide (GALP) on luteinizing hormone-releasing hormone-mediated luteinizing hormone (LH) secretion in male rats.
Enocrinology, 142 (2001), pp. 3693-3696
[88.]
A. Seth, S. Stanley, P. Jethwa, J. Gardiner, M. Ghatei, S. Bloom.
Galanin-like peptide stimulates the release of gonadotropin-releasing hormone in vitro and may mediate the effects of leptin on the hypothalamo-pituitary-gonadal axis.
Endocrinology, 145 (2004), pp. 2743-2750
[89.]
S. Kumano, H. Matsumoto, Y. Takatsu, J. Noguchi, C. Kitada, T. Ohtaki.
Changes in hypothalamic expression levels of galanin-like peptide in rat and mouse models support that it is a leptin-target peptide.
Endocrinology, 38 (2003), pp. 497-503
[90.]
J. Shen, A.L. Gundlach.
Galanin-like peptide mRNA alterations in arcuate nucleus and neural lobe of streptozotocin-diabetic and obese Zucker rats. Further evidence for leptin-dependent and independent regulation.
Neuroendocrinology, 79 (2004), pp. 327-337
[91.]
E.M. Whitaker, A.C. Robinson, K.M. Rayfield, G.R. Hervey.
Thyroid function in male Zucker rats exposed to cold.
J Exp Physiol, 73 (1988), pp. 1029-1031
[92.]
D. Richard, R. Rivest, N. Naimi, E. Timofeeva, S. Rivest.
Expression of corticotrophin-releasing factor and its receptors in the brain of lean and obese Zucker rats.
Endocrinology, 137 (1996), pp. 4786-4795
[93.]
Y. Yamamoto, Y. Ueta, H. Yamashita, K. Asayama, A. Shirahata.
Expressions of the prepro-orexin and orexin type 2 receptor genes in obese rat.
Petides, 23 (2002), pp. 1689-1696
[94.]
E.M. Kim, O’Hare, M.K. Grace, C.C. Welch, C.J. Billington, A.S. Levine.
ARC POMC mRNA and PVN α-MSH are lower in obese relative to lean Zucker rats.
Brain Res, 862 (2000), pp. 11-16
[95.]
J. Korner, S.C. Chua Jr, J.A. Williams, R.L. Leibel, S.L. Wardlaw.
Regulation of hypothalamic proopiomelanocortin by leptin in lean and obese rats.
Neuroendocrinology, 70 (1999), pp. 377-383
Copyright © 2006. Sociedad Española de Endocrinología y Nutrición
