EFFECT OF VISFATIN ON TESTICULAR STEROIDOGENESIS IN PURIFIED LEYDIG CELLS
Abstract
Background: Lower testosterone levels have been reported in men suffering from diabetes mellitus.Men with insulin resistance states such as obesity and type 2 diabetes mellitus have significantly lowertestosterone levels than age-matched normal weight and non-diabetic controls. Adipose tissue secretesvariety of adipokinesincluding adiponectin, resistin, visfatin, TNF-α. The study was designed to studythe effect of visfatin on testicular steroidogenesis in purified Leydig cell in vitro. Methods: Leydigcells of Sprague Dawley rats were isolated and purified by Percoll. Cells were incubated for 3 hourswith/without visfatin in the presence/absence of LH and intracellular signalling blockers including PKCblocker, PKA blocker and Raf1/Ras blocker. Cell culture extracts were stored at -80 ℃ before analysisfor levels of testosterone hormone by ELISA. Results: Visfatin increased testosterone production(p<0.001) from cultured Leydig cells. Raf1/Ras blocker decreased visfatin induced steroidogenesis(p<0.001). Conclusion: Visfatin increased testicular steroidogenesis from Leydig cells in vitro modelsand operates through variety of enzymes, but especially through Ras/Raf1 kinase enzymes.Keywords: Visfatin, adipocytokines, Leydig cells, testicular steroidogenesisReferences
Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi
D, at al. Increasing insulin resistance is associated with a
decrease in Leydig cell testosterone secretion in men. J Clin
Endocrinol Metab 2005;90(5):2636–41.
Andersson B, Mårin P, Lissner L, Vermeulen A, Björntorp P.
Testosterone concentrations in women and men with NIDDM.
Diabetes Care 1994;17(5):405–11.
Abate N, Haffner SM, Garg A, Peshock RM, Grundy SM. Sex
steroid hormones, upper body obesity, and insulin resistance. J
Clin Endocrinol Metab 2002;87(10):4522–7.
Tsai EC, Matsumoto AM, Fujimoto WY, Boyko EJ. Association
of bioavailable, free, and total testosterone with insulin resistance:
influence of sex hormone-binding globulin and body fat.
Diabetes Care 2004;27(4):861–8.
Saez JM. Leydig cells: endocrine, paracrine, and autocrine
regulation. Endocr Rev 1994;15(5):574–626.
Lin T, Haskell J, Vinson N, Terracio L. Characterization of
insulin and insulin-like growth factor I receptors of purified
Leydig cells and their role in steroidogenesis in primary culture: a
comparative study. Endocrinology 1986;119(4):1641–7.
Bebakar WM, Honour JW, Foster D, Liu YL, Jacobs HS.
Regulation of testicular function by insulin and transforming
growth factor-beta. Steroids 1990;55(6):266–70.
Vettor R, De Pergola G, Pagano C, Englaro P, Laudadio E,
Giorgino F, et al. Gender differences in serum leptin in obese
people: relationships with testosterone, body fat distribution and
insulin sensitivity. Eur J Clin Invest 1997;27(12):1016–24.
Luukkaa V, Pesonen U, Huhtaniemi I, Lehtonen A, Tilvis R,
Tuomilehto J, et al. Inverse correlation between serum
testosterone and leptin in men. J Clin Endocrinol Metab
;83(9):3243–6.
Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M,
Kishimoto K, et al. Visfatin: a protein secreted by visceral fat that
mimics the effects of insulin. Science 2005;307(5708):426–30.
Sethi JK, Vidal-Puig A. Visfatin: the missing link between intraabdominal obesity and diabetes? Trends Mol Med
;11(8):344–7.
Zwain IH, Morris PL, Cheng CY. Identification of an inhibitory
factor from a Sertoli clonal cell line (TM4) that modulates adult
rat Leydig cell steroidogenesis. Mol Cell Endocrinol
;80:115–26.
Sharpe RM, Fraser HM. The role of LH in regulation of Leydig
cell responsiveness to an LHRH agonist. Mol Cell Endocrinol
;33:131–46.
Aldred LF. Cooke BA. The effect of cell damage on the density
and steroidogenic capacity of rat testis Leydig cells, using an
NADH exclusion test for determination of viability. J Steroid
Biochem 1983;18:411–4.
Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning
and characterization of the cDNA encoding a novel human preB-cell colony enhancing factor. Mol Cell Biol 1994;14:1431–7.
Gray RE, Tanner CJ, Pories WJ, MacDonald KG, Houmard JA.
Effect of weight loss on muscle lipid content in morbidly obese
subjects. Am J Physiol Endocrinol Metab 2003;284(4):E726–32.
Saez JM, Avallet O, Naville D, Perrard-Sapori MH, Chatelain
PG. Sertoli-Leydig cell communications. Ann NY Acad Sci
;564:210–31.
Varma V, Yao-Borengasser A, Rasouli N, Bodles AM,
Phanavanh B, Lee MJ, et al. Human visfatin expression:
relationship to insulin sensitivity, intramyocellular lipids, and
inflammation. J Clin Endocrinol Metab 2007;92(2):666–72.
Clark BJ. Wells J, King SR, Stocco DM. The purification,
cloning, and expression of a novel luteinizing hormone-induced
mitochondrial protein in MA-10 mouse Leydig tumor cells.
Characterization of the steroidogenic acute regulatory protein
(StAR). J Biol Chem 1994;269:28314–22.
Stocco DM, Clark BJ. Regulation of the acute production of
steroids in steroidogenic cells. Endocr Rev 1996;17:221–44.
Tena-Sempere M, Pinilla L, González LC, Diéguez C,
Casanueva FF, Aguilar E. Leptin inhibits testosterone secretion
from adult rat testis in vitro. J Endocrinol 1999;161(2):211–8.
Published
Issue
Section
License
Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.
USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.