Immunohistomorphometric Changes of The Pituitary Gonadotropic Cells After Testosterone Application in a Rat Model of the Andropause

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Abstract

Andropause, the culminating phase of male ageing, is characterized by deregulation of the hypothalamic-pituitarygonadal axis and low circulating free testosterone. The aim of this study was to investigate the immunohistomorphometric characteristics of the pituitary gonadotropic i.e. follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) producing cells after testosterone application in a rat model of the andropause. Middle-aged Wistar rats were divided into orchidectomized (ORX; n=8) and testosterone treated orchidectomized (ORX+T; n=8) groups. Testosterone propionate (5 mg/kg b.m./day) was administered for three weeks, while the ORX group received the vehicle alone. Immunohistochemically stained FSH and LH cells underwent morphometric and optical density-related analysis, while circulating concentrations of the sex steroids were measured by immunoassays. Serum concentrations of testosterone and estradiol were significantly (p<0.05) increased by 24 and 2.7 fold respectively, compared to the ORX group. The volume of FSH and LH cells was significantly (p<0.05) decreased by 51.3% and 56.6% respectively, in comparison with ORX rats. Relative volume density of FSH and LH cells was also significantly (p<0.05) decreased by 54.0% and 72.8% respectively, compared to the ORX group. Results related to the optical density of gonadotropic cells (reflecting their hormonal content) were in line with the morphometric findings i.e. this parameter of FSH and LH cells was significantly (p<0.05) decreased by 25.7% and 16.2% respectively, in comparison with ORX rats. Conclusion: In conclusion, applied testosterone increased the serum concentrations of sex steroids, as well as it decreased morphometric parameters and optical density of gonadotropic cells in ORX rats.

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  • 1. Wespes E. Schulman C.C. (2002). Male andropause: myth reality and treatment. Int J Impot Res. Suppl 1 93-98. https://doi.org/10.1038/sj.ijir.3900798 PMid:11850741

  • 2. Morales A. (2004). Andropause (or symptomatic late-onset hypogonadism): facts fiction and controversies. Aging Male 7 297-303. https://doi.org/10.1080/13685530400016664 PMid:15799125

  • 3. Chahal H.S. Drake W.M. (2007). The endocrine system and ageing. J Pathol. 211 173-180. https://doi.org/10.1002/path.2110 PMid:17200939

  • 4. Jiang M. Huhtaniemi I. (2004). Polymorphisms in androgen and estrogen receptor genes: effects on male aging. Exp Gerontol. 39 603-611. https://doi.org/10.1016/j.exger.2004.06.017 PMid:15582276

  • 5. Wang X.J. Stocco D.M. (2005). The decline in testosterone biosynthesis during male aging: A consequence of multiple alterations. Mol Cell Endocrinol. 238 1-7. https://doi.org/10.1016/j.mce.2005.04.009 PMid:15939533

  • 6. Bonavera J.J. Swerdloff R.S. Leung A. Lue Y.H. Baravarian S. Superlano L. Sinha-Hikim A.P. Wang C. (1997). In the male brown-Norway (BN) male rat reproductive aging is associated with decreased LH-pulse amplitude and area. J Androl.18 359-365. PMid:9283947

  • 7. Gruenewald D.A. Naai M.A. Marck B.T. Matsumoto A.M. (2000). Age-related decrease in hypothalamic gonadotropin-releasing hormone (GnRH) gene expression but not pituitary responsiveness to GnRH in the male Brown Norway rat. J Androl. 21 72-84. PMid:10670522

  • 8. Elmlinger M.W. Dengler T. Weinstock C. Kuehnel W. (2003). Endocrine alterations in the aging male. Clin Chem Lab Med. 41 934-941. https://doi.org/10.1515/CCLM.2003.142 PMid:12940521

  • 9. Hermann M. Untergasser G. Rumpold H. Berger P. (2000). Aging of the male reproductive system. Exp Gerontol. 35 1267-1279. https://doi.org/10.1016/S0531-5565(00)00159-5

  • 10. Beg S. Al-Khoury L. Cunningham G.R. (2008). Testosterone replacement in men. Curr Opin Endocrinol Diabetes Obes. 15 364-370. https://doi.org/10.1097/MED.0b013e328305081a PMid:18594278

  • 11. Singh P. (2013). Andropause: current concepts. Indian J Endocrinol Metab. 17 621-629. https://doi.org/10.4103/2230-8210.123552 PMid:24910824 PMCid:PMC4046605

  • 12. Theodoraki A. Bouloux P.M. (2009). Testosterone therapy in men. Menopause Int. 15 87-92. https://doi.org/10.1258/mi.2009.009025 PMid:19465676

  • 13. Kunelius P. Lukkarinen O. Hannuksela M.L. Itkonen O. Tapanainen J.S. (2002). The effects of transdermal dihydrotestosterone in the aging male: a prospective randomized double blind study. J Clin Endocrinol Metab. 87 1467-1472. https://doi.org/10.1210/jcem.87.4.8138 PMid:11932266

  • 14. Kitahara S. Winters S.J. Oshima H. Troen P. (1991). Effects of gonadal steroids on follicle-stimulating and luteinizing hormone secretion by pituitary cells from castrated and intact male rats. Biol Reprod. 44 121-126. https://doi.org/10.1095/biolreprod44.1.121 PMid:1901736

  • 15. Okada Y. Fujii Y. Moore J.P. Jr. Winters S.J. (2003). Androgen receptors in gonadotrophs in pituitary cultures from adult male monkeys and rats. Endocrinology. 144 267-273. https://doi.org/10.1210/en.2002-220770 PMid:12488354

  • 16. Ajdžanović V. Šošić-Jurjević B. Filipović B. Trifunović S. Brkić D. Sekulić M. Milošević V. (2009). Genistein affects the morphology of pituitary ACTH cells and decreases circulating levels of ACTH and corticosterone in middle-aged male rats. Biol Res. 42 13-23.

  • 17. Ajdžanović V. Šošić-Jurjević B. Filipović B. Trifunović S. Milošević V. (2011). Daidzein effects on ACTH cells: immunohistomorphometric and hormonal study in an animal model of the andropause. Histol Histopathol. 26 1257-1264. PMid:21870329

  • 18. Ajdžanović V. Medigović I. Živanović J. Šošić-Jurjević B. Trifunović S. Tanić N. Milošević V. (2014). Immuno-histomorphometric and –fluorescent characteristics of GH cells after treatment with genistein or daidzein in an animal model of andropause. Acta Vet (Beograd). 64 93-104. https://doi.org/10.2478/acve-2014-0010

  • 19. Filipović B. Šošić-Jurjević B. Ajdžanović V. Pantelić J. Nestorović N. Milošević V. Sekulić M. (2013). The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis. J Anat. 222 313-320. https://doi.org/10.1111/joa.12013 PMid:23171170 PMCid:PMC3582251

  • 20. Sternberger L.A. Hardy P.H. Jr. Cuculis J.J. Meyer H.G. (1970). The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 18 315-333. https://doi.org/10.1177/18.5.315 PMid:4192899

  • 21. Medigović I. Manojlović-Stojanoski M. Trifunović S. Ristić N. Milošević V. Zikić D. Nestorović N. (2012). Effects of genistein on gonadotropic cells in immature female rats. Acta Histochem. 114:270-5. https://doi.org/10.1016/j.acthis.2011.06.003 PMid:21703666

  • 22. Poole M.C. Kornegay 3rd W.D. (1982). Cellular distribution within the rat adenohypophysis: a morphometric study. Anat Rec. 204 45-53. https://doi.org/10.1002/ar.1092040107 PMid:7149283

  • 23. Ruifrok A.C. Johnston D.A. (2001). Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol. 23 291-299. PMid:11531144

  • 24. Varghese F. Bukhari A.B. Malhotra R. De A. (2014). IHC profiler: an open source plugin for the quantitative evaluation and automated scoring of immunohistochemistry images of human tissue samples. PLoS One. 9:e96801. https://doi.org/10.1371/journal.pone.0096801 PMid:24802416 PMCid:PMC4011881

  • 25. Ajdžanović V. Jarić I. Živanović J. Filipović B. Ristić N. Miler M. Milošević V. (2015). Testosterone application decreases the capacity for ACTH and corticosterone secretion in a rat model of the andropause. Acta Histochem. 117 528-535. https://doi.org/10.1016/j.acthis.2015.04.002 PMid:25940766

  • 26. Ajdžanović V. Jarić I. Živanović J. Filipović B. Šošić-Jurjević B. Ristić N. Stanković S. Milošević V. (2016). Histological parameters of the adrenal cortex after testosterone application in a rat model of the andropause. Histol Histopathol. 31:1209-1220. PMid:26951517

  • 27. Banerjee A. Anjum S. Verma R. Krishna A. (2012). Alteration in expression of estrogen receptor isoforms alpha and beta and aromatase in the testis and its relation with changes in nitric oxide during aging in mice. Steroids 77 609-620. https://doi.org/10.1016/j.steroids.2012.02.004 PMid:22366072

  • 28. Arimura A. Shino M. de la Cruz K.G. Rennels E.G. Schally A.V. (1976). Effect of active and passive immunization with luteinizing hormone-releasing hormone on serum luteinizing hormone and follicle stimulating hormone levels and the ultrastructure of the pituitary gonadotrophs in castrated male rats. Endocrinology 99 291-303. https://doi.org/10.1210/endo-99-1-291 PMid:780100

  • 29. Lindzey J. Wetsel W.C. Couse J.F. Stoker T. Cooper R. Korach K.S. (1998). Effects of castration and chronic steroid treatments on hypothalamic gonadotropin-releasing hormone content and pituitary gonadotropins in male wild-type and estrogen receptor-alpha knockout mice. Endocrinology139 4092-40101. https://doi.org/10.1210/endo.139.10.6253 PMid:9751487

  • 30. Mitchner N.A. Garlick C. Ben-Jonathan N. (1998). Cellular distribution and gene regulation of estrogen receptors alpha and beta in the rat pituitary gland. Endocrinology 139 3976-3983. https://doi.org/10.1210/endo.139.9.6181 PMid:9724053

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