Melatonin anterior pituitary of the female Wistar rat(3)

282

Osamura well-developed, double-layered, concentric roughet al. [22] found that PRLwas located in theendoplasmic reticulum. Bromocriptine caused thecytoplasm to shrink and unsecreted PRLaggregate, with the abrogation of exocytosis. Eljarmakgranules toet alistration reduced the volumes of the cell, the rough. [23] found that continuous bromocriptine admin-endoplasmic reticulum, and the Golgi complex. Theultrastructural improvements conferred by melatoninprovided strong evidence for its efficacy as a thera-peutic. Melatonin has been shown to reduce tumor sizeand serum PRLexocytosis or disruption of RER.

concentration without the misplacedfor 4 weeks caused the accumulation of large PRLIn the present study, administration of melatoninsecretory granules in loosened RER, suggesting mela-tonin may inhibit the exocytosis of PRL-containinggranules and reduce the expression of PRLnegative feedback. The structural improvements to thethroughconcentric RER support this.

product of the pineal body and a natural tumorThe anti-cancer activity of melatonin, primarily ainhibitor, has been related to its immune-regulatory,anti-proliferation, and anti-oxidant effects. Angiogene-sis is a key step in the development and metastasis ofmost tumors, including pituitary tumors. However,compelling data concerning melatonin in angiogenesisare not yet available. Soybir melatonin could function in angiogenesis and woundet al. [24] found thatrepair, which was related to the regulatory effects ofmelatonin on monocytes, cytokines, and fibroblastomacells. Cui it the growth of cultured umbilical vein endothelialet al. [25] found that melatonin could inhib-cells, inducing apoptosis by regulating the cell size,which involved p53 and Bax/Bcl expression changes.EGF and VEGF are involved in angiogenesis, stimu-lating cellular proliferation, promoting vasculariza-tion, and sustaining the integrity of vessels, meaningthese proteins play an important role in tumor metasta-sis [26-28]. The present study demonstrated DES-induced upregulation of VEGF and MMP-9, confirm-ing a role for estrogen in angiogenesis in the rat ante-rior pituitary. Melatonin has been reported to down-regulate MMP-9 expression and activity in severalpathological states in rodents, such as reperfusion-induced hemorrhage following transient focal cerebralischemia and spinal cord injury [29-31]. The inhibito-ry effects of melatonin may be associated with reducedexpression of TNF-inhibitor of metalloproteinase (TIMP)-1 [30,32]. αand elevated expression of tissueMMP-9, accompanied by an improvement in H+E score,Melatonin reduced the expression of both VEGF andsuggesting these molecules are targets of melatonin inthe treatment of estrogen-induced pituitary malfunction.Further study is needed to determine why AQP-1 wasupregulated by DES and not suppressed by melatonin.

©Polish Histochemical et Cytochemical Society

Folia Histochem Cytobiol. 2010:48(2): 282(278-283) 10.2478/v10042-010-0023-1

W. Zhaoet al.

References

[ 1]Gooren LJ, Assies J, Asscheman H, de Slegte R, van Kessel

H. Estrogen-induced prolactinoma in a man. J Clin EndocrinolMetab. 1988;66:444-446.

[ 2]Kaplan SE, De Nicola AF. Protein and RNAsynthesis in pitu-itary tumors from F344 rats given implants of estrogen. J NatlCancer Inst.1976;56:37-42.

[ 3]Katznelson L. Hypogonadism in patients with acromegaly:

data from the multi-center acromegaly registry pilot study.Clin Endocrinol. 2001; 54:183-188.[ 4] Walker BE. Tumors in female offspring of control and

diethylstilbestrol-exposed mice fed high-fat diets. J natlCancer Inst. 1990;82:50-54.

[ 5]Wu YH, Zhou JN, Balesar R. Distribution of MT1 melatonin

receptor immunoreactivity in the human hypothalamus andpituitary gland: colocalization of MT1 with vasopressin, oxy-tocin, and corticotropin-releasing hormone. J Comp Neurol.2006;499(6):897-910.

[ 6]Alvira D, Tajes M, Verdaguer E. Inhibition of the cdk5/p25

fragment formation may explain the antiapoptotic effects ofmelatonin in an experimental model of Parkinson's disease. JPineal Res. 2006;40(3):251-258.

[ 7]Macchi MM, Bruce JN. Human pinel physiology and func-tional significance of melatonin. Front Neuroendocrinol.2004;25:177-195.

[ 8]Karasek M, Pawlikowski M. Antiproliferative effects of mela-tonin and CGP52608. Biol Signals Recept. 1999;8:75-78.[ 9]Gao L, Xu RK, Pang CS. Inhibitory effect of melatonin on the

development of pituitary prolactin-producing tumors inducedby 17-beta-estradiol. Zhongguo Yi Xue Ke Xue Yuan Xue Bao.2001;23:49-53.

[10]Gao L, Yang QH, Xu RK. Melatonin inhibits the proliferation

of pituitary prolactin-secreting tumor by suppressing theenhancer elements mutation of PRLgene in the rat. Sheng LiXue Bao. 2005;57:319-327.

[11]Yang QH, Xu JN, Xu RK. Antiproliferative effects of mela-tonin on the growth of rat pituitary prolactin-secreting tumorcells in vitro. J Pineal Res. 2007;42:172-179.

[12]Turner HE, Nagy Z, Gatter KC, Esiri MM, Harris AL, Wass

JA. Angiogenesis in pituitary adenomas and the normal pitu-itary gland. J Clin Endocrinol Metab. 2000;85:1159-1162.[13]Turner HE, Nagy Z, Gatter KC, Esiri MM, Harris AL, Wass

JA. Angiogenesis in pituitary adenomas – relationship toendocrine function, treatment and outcome. J Endocrinol.2000;165:475-481.

[14]Horiguchi H, Jin L, Ruebel KH, Scheithauer BW, Lloyd RV.

Regulation of VEGF-A, VEGFR-I, thrombospondin-1, -2,and -3 expression in a human pituitary cell line (HP75) byTGFbeta1, bFGF, and EGF. Endocrine. 2004;24:141-146.[15]Lloyd RV, Scheithauer BW, Kuroki T. Vascular Endothelial

Growth Factor (VEGF) Expression in Human Pituitary Ade-nomas and Carcinomas. Endocr Pathol. 1999;10:229-235.[16]Zhao W, Shen H, Yuan F, Li G, Sun Y, Shi Z, Zhang Y, Wang

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