BLOKADA SINTEZE AZOT MONOKSIDA STIMULIŠE AKTIVNOST KORTEKSA NADBUBREŽNE ŽLEZDE
Sažetak
Cilj: Iako je poznato je da azot monoksid moduliše aktivnost hipotalamo-hipofizno-nadbubrežne osovine, funkcionalni značaj tog delovanja nije rasvetljen. Pored toga, dejstvo azot monoksida na kortikalnu ekspresiju glukokortikoidnog receptora nije istraženo. Cilj ovog rada bio je da se ispita uticaj endogenog azot monoksida na strukturu i funkciju kore nadbubrežne žlezde pacova i adrenokortikalnu ekspresiju glukokortikoidnog receptora.
Metode: Odrasle ženke pacova Wistar soja u metestrusnoj fazi ciklusa tretirane su Nω-nitro-L-arginin metil esterom (L-NAME), inhibitorom sve tri izoforme azot monoksid sintaze, u dozi 30 mg/kg, s.c. Koncentracije ACTH i kortikosterona u krvi određene su radioimunološkom metodom. Na parafinskim presecima nadbubrežne žlezde izvršena je stereološka i imunohistohemijska analiza korteksa.
Rezultati: Blokada sinteze azot monoksida značajno povećava koncentracije ACTH i kortikosterona u krvi. Stereološka analiza je pokazala da tretman sa L-NAME značajno smanjuje numeričku gustinu ćelija u svim kortikalnim zonama. U skladu sa smanjenom numeričkom gustinom, L-NAME značajno povećava volumen ćelija u sve tri zone korteksa. Inhibicija sinteze azot monoksida smanjuje ekspresiju glukokortikoidnog receptora u zoni fascikulati i zoni retikularis.
Zaključak: Dobijeni rezultati ukazuju da endogeni azot monoksid inhibiše aktivnost kore nadbubrežne žlezde i da moduliše ekspresiju glukokortikoidnog receptora.
Reference
Stern JE. Nitric oxide and homeostatic control: an intercellular signalling molecule contributing to autonomic and neuroendocrine integration? Prog Biophys Mol Biol 2004; 84: 197-215.
Lundberg JO, Weitzberg E. NO-synthase independent NO generation in mammals. Biochem Biophys Res Commun 2010; 396: 39-45.
Thippeswamy T, McKay JS, Quinn JP, Morris R. Nitric oxide, a biological double-faced janus--is this good or bad? Histol Histopathol 2006; 21: 445-58.
Kots AY, Bian K, Murad F. Nitric oxide and cyclic GMP signaling pathway as a focus for drug development. Curr Med Chem 2011; 18: 3299-305.
Aron DC, Findling JW, Tyrrell JB. Glucocorticoids and adrenal androgens. In: Gardner DG, Shoback D (eds). Geenspan`s basic and clinical endocrinology. Mc Graw Hill Companies, 2007; 346-95.
Thomas M, Keramidas M, Monchaux E, Feige JJ. Dual hormonal regulation of endocrine tissue mass and vasculature by adrenocorticotropin in the adrenal cortex. Endocrinology 2004; 145: 4320-29.
Buckingham JC. Glucocorticoids: exemplars of multi-tasking. Br J Pharmacol 2006; 147: 258-68.
Paust HJ, Loeper S, Else T, et al. Expression of the glucocorticoid receptor in the human adrenal cortex. Exp Clin Endocrinol Diabetes 2006; 114: 6-10.
Root B, Abrassart J, Myers DA, Monau T, Ducsay CA. Expression and distribution of glucocorticoid receptors in the ovine fetal adrenal cortex: effect of long-term hypoxia. Reprod Sci 2008; 15: 517-28.
Mancuso C, Navarra P, Preziosi P. Roles of nitric oxide, carbon monoxide and hydrogen sulfide in the regulation of the hypothalamic-pituitary-adrenal axis. J Neurochem 2010; 113: 563-75.
Cymeryng CB, Lotito SP, Colonna C, et al. Expression of nitric oxide synthases in rat adrenal zona fasciculata cells. Endocrinology 2002; 143: 1235-42.
Peterson JK, Moran F, Conley AJ, Bird IM. Zonal expression of endothelial nitric oxide synthase in sheep and rhesus adrenal cortex. Endocrinology 2001; 142: 5351-63.
Ducsay CA, Myers DA. eNOS activation and NO function: Differential control of steroidogenesis by nitric oxide and its adaptation with hypoxia. J Endocrinol 2011; 210: 259-69.
Kalsbeek A, van der Spek R, Lei J, Endert E, Buijs RM, Fliers E. Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis. Mol Cell Endocrinol 2012; 349: 20-29.
López-Figueroa MO, Day HE, Akil H, Watson SJ. Nitric oxide in the stress axis. Histol Histopathol 1998; 13: 1243-52.
Sica M, Martini M, Viglietti-Panzica C, Panzica G. Estrous cycle influences the expression of neuronal nitric oxide synthase in the hypothalamus and limbic system of female mice. BMC Neurosci 2009; 10: 78.
Atkinson HC, Waddell BJ. Circadian variation in basal plasma corticosterone and adrenocorticotropin in the rat: sexual dimorphism and changes across the estrous cycle. Endocrinology 1997; 138: 3842-8.
Adams ML, Nock B, Truong R, Cicero TJ. Nitric oxide control of steroidogenesis: endocrine effects of NG-nitro-L-arginine and comparisons to alcohol. Life Sci 1992; 50: PL35-40.
Giordano M, Vermeulen M, Trevani AS, Dran G, Andonegui G, Geffner JR. Nitric oxide synthase inhibitors enhance plasma levels of corticosterone and ACTH. Acta Physiol Scand 1996; 157: 259-64.
Hanke CJ, Drewett JG, Myers CR, Campbell WB. Nitric oxide inhibits aldosterone synthesis by a guanylyl cyclase-independent effect. Endocrinology 1998; 139: 4053-60.
Cymeryng CB, Dada LA, Podestá EJ. Effect of nitric oxide on rat adrenal zona fasciculata steroidogenesis. J Endocrinol 1998; 158: 197-203.
Monau TS, Vargas VE, Zhang L, Myers DA, Ducsay CA. Nitric Oxide inhibits ACTH-induced cortisol production in near-term, long-term hypoxic ovine fetal adrenocortical cells. Reproductive Sciences 2010; 17(10): 955-62.
Bugajski J, Borycz J, Gadek-Michalska A, Głód R. Effect of L-NAME, a specific nitric oxide synthase inhibitor, on corticotropin-releasing hormone-elicited ACTH and corticosterone secretion. J Physiol Pharmacol 1998; 49: 607-16.
Boyle B, Butz H, Liko I, et al. Expression of glucocorticoid receptor isoforms in human adrenocortical adenomas. Steroids 2010; 75: 695-700.
Tacon LJ, Soon PS, Gill AJ, et al. The glucocorticoid receptor is overexpressed in malignant adrenocortical tumors. J Clin Endocrinol Metab 2009; 94: 4591-99.
Kalinyak JE, Dorin RI, Hoffman AR, Perlman AJ. Tissue-specific regulation of glucocorticoid receptor mRNA by dexamethasone. J Biol Chem 1987; 262: 10441-44.
Da J, Chen L, Hedenstierna G. Nitric oxide up-regulates the glucocorticoid receptor and blunts the inflammatory reaction in porcine endotoxin sepsis. Crit Care Med 2007; 35: 26-32.