The effect of testosterone supplementation on morphometry and VEGF expression level of thoracic aorta in aged mice
Öz
The aim of this study was to determine the effects of the testosterone hormone level on morphometry and vascular endothelial growth factor (VEGF) expression level of thoracic aorta of aged mice using histological and molecular techniques. A total of 30 aged mice (15 males and 15 females) were enrolled in 3 study groups: sham operation group (Control), gonadectomy group (G) and gonadectomy and testosterone supplementation group (GTS). Serum testosterone levels were measured by ELISA. Intima and media thickness and inner diameter of thoracic aorta were measured by morphometric investigation. The levels of the angiogenic factor, VEGF (vascular endothelial growth factor) mRNA in thoracic aorta were determined by RT-PCR. Although the alterations in the level of testosterone had no significant effects on intima or media thickness of the male thoracic aorta, in female, there was a significant increase (p<0.01) on intimal thickness in thoracic aorta following gonadectomy and hormone supplementation. The largest inner diameter was in testosterone supplementation groups of both sexes. Gonadectomie operation caused decrease in VEGF mRNA levels of thoracic aorta in male (p<0.05) and female mice. Interestingly, testosterone replacement caused an important decrease (p<0.01) in the expression of VEGF of aorta in female whereas resulted with an increase in male. Present results showed that testosterone hormone had different angiogenic effects on thoracic aorta in male and female aged mice. Additionally, gonadectomie operation in aged mice caused decrease in the level of VEGF mRNA levels in both sexes
Anahtar Kelimeler
Kaynakça
- Alexandersen P, Christiansen C (2004): The aging male: Testosterone deficiency and testosterone replacement. An up-date. Atherosclerosis, 173, 157-169.
- Cai J, Hong Y, Weng C, et al. (2011): Androgen stimulates endothelial receptor/VEGF/cyclin A-mediated mechanism. Am J Physiol Heart Circ Physiol, 300, 1210-1221. androgen
- Crossman OA (1937): Modification of Mallory’s connective tissue stain with a discussion of the principles involved. Anat Rec, 69, 31.
- Doğan BA, Karakılıç E, Tuna MM, et al. (2015): Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism. Clin Endocrinol, 82, 422-428.
- Hak AE, Westendorp IC, Pols HA, et al. (2007): High- dose testosterone is associated with atherosclerosis in postmenopausal women. Maturitas, 56, 153-160.
- Hanke H, Lenz C, Hess B, et al. (2001): Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall. Circulation, 103, 1382-1385.
- Hsu YJ, Dimke H, Schoeber JP, et al. (2010): Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins. Kidney Int, 77, 601-608.
- Iliescu R, Reckelhoff JF (2006): Testosterone and vascular reactivity. Clin Sci, 111, 251-252.
- Jesmin S, Hattori Y, Sakuma I, et al. (2003): Estrogen deprivation and replacement modulate cerebral capillary density with vascular expression of angiogenic molecules in middle-aged female rats. J Cereb Blood Flow Metab, 23, 181-189.
- Kearney ML, Hurn FPD (2004): Testosterone as a modulator of vascular behavior. Biol Res Nurs, 5, 276-285.
- Li S, Guo Y, Zhu P, Yang T (2013): Role of Ox-LDL/LOX- 1/NF-κB signaling pathway in regulation of atherosclerotic plaque growth by testosterone in male rabbits. Vascul Pharmacol, 59, 131-137.
- Mathur A, Malkin C, Saeed B, et al. (2009): Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. Eur J Endocrinol, 161, 443- 449.
- O’Connor EK, Ivey JR, Bowles DK (2012): Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine. Biol Sex Differ, 3, 10.
- Otrock ZK, Mahfouz RAR, Makarem JA, et al. (2007): Understanding the biology of angiogenesis: Review of the most important molecular mechanisms. Blood Cells Mol Dis, 39, 212-220.
- Saad F (2012): Androgen therapy in men with testosterone deficiency: Can testosterone reduce the risk of cardiovascular disease? Diabetes Metab Res Rev, 28, 52- 59.
- Shidaifat F, Gharaibeh M, Bani-Ismail Z (2007): Effect of castration on extracellular matrix remodeling and angiogenesis of the prostate gland. Endocr J, 54, 521-529.
- Sieveking DP, Lim P, Chow RWY, et al. (2010): A sex- specific role for androgens in angiogenesis. J Exp Med, 207, 345-352.
- Soisson V, Brailly-Tabard S, Empana JP, et al. (2012): Low plasma testosterone and elevated carotid intima-media thickness: Importance of low-grade inflammation in elderly men. Atherosclerosis, 223, 244-249.
- Sordello S, Bertrand N, Plouet J (1998): Vascular endothelial growth factor is up-regulated in vitro and in vivo by androgens. Biochem Biophys Res Commun, 251, 287-290.
- Tsujimura A, Yamamoto R, Okuda H, et al. (2012): Low serum free testosterone level is associated with carotid intima-media thickness in middle-aged Japanese men. Endocr J, 59, 809-815.
- Wang W, Chao S, Xian W (2002): Alteration of vascular response to norepinephrine, calcitonin gene-related peptide, and acetylcholine in orchidectomized rats. Acta Pharm Sinic, 23, 985-990.
- Yıldız O (2007): Vascular smooth muscle and endothelial functions in aging. Ann N Y Acad Sci, 1100, 353-360. Geliş tarihi: 05.01.2016 / Kabul tarihi: 12.04.2017 Address for correspondence: Prof. Dr. İlknur DABANOĞLU Adnan Menderes University, Faculty of Veterinary Medicine, Department of Anatomy Işıklı Köyü 09016 Aydın, Turkey. Tel: + 90 256 247 0700-242 e-mail: dabanf@yahoo.com
The effect of testosterone supplementation on morphometry and VEGF expression level of thoracic aorta in aged mice
Öz
Çalışmanın amacı, yaşlı farelerde testosteron hormonu seviyesinin aorta thoracica’daki anjiogenik etkisini ve vaskülo endoteliyal büyüme faktörünün (VEGF) ekspresyon düzeyini histolojik ve moleküler yöntemlerle belirlemektir. Çalışmada 30 adet yaşlı fare (15 erkek ve 15 dişi) üç farklı gruba ayrıldı. Bu gruplar; yalancı gonadektomi operasyonu yapılan kontrol grubu, gonadektomi operasyonu yapılan (G) grup ve hem gonadektomi hem de testosteron takviyesi yapılan (GTS) gruptur. Hayvanların kanındaki testosteron seviyesi ELISA testi ile ölçüldü. Aorta thoracica’nın intima ve media kalınlıkları ile iç çapı morfometrik incelemelerle belirlendi. Aorta thoracica’daki anjiogenik faktörlerden biri olan VEGF mRNA miktarı ise RT-PCR tekniği ile tespit edildi. Testosteron seviyesindeki değişimlerin erkeklerde aorta thoracica’nın intima ve media kalınlıklarında önemli bir etkisinin olmadığı saptandı. Dişilerde ise gonadektomi operasyonundan sonra yapılan hormon takviyesinin intima kalınlığında bir artışa (p<0.01) neden olduğu belirlendi. Aorta thoracica’nın iç çapı en geniş olarak her iki cinste de GTS grubunda belirlendi. Gonadektomi operasyonunun VEGF mRNA miktarı üzerinde erkek (p<0.05) ve dişilerde bir azalmaya neden olduğu saptandı. Testosteron takviyesi aorta thoracica’daki VEGF mRNA ekspresyon seviyesinde dişilerde azalmaya (p<0.01) neden olurken, erkeklerde artışa neden olmaktadır. Elde edilen sonuçlara göre, testosteron hormonunun yaşlı erkek ve dişi farelerde farklı anjiyogenik etkiye sahip olduğu belirlendi. Ayrıca her iki cinsiyette de gonadektomi operasyonunun VEGF’nin mRNA seviyesinde azalmaya neden olduğu saptandı
Anahtar Kelimeler
Kaynakça
- Alexandersen P, Christiansen C (2004): The aging male: Testosterone deficiency and testosterone replacement. An up-date. Atherosclerosis, 173, 157-169.
- Cai J, Hong Y, Weng C, et al. (2011): Androgen stimulates endothelial receptor/VEGF/cyclin A-mediated mechanism. Am J Physiol Heart Circ Physiol, 300, 1210-1221. androgen
- Crossman OA (1937): Modification of Mallory’s connective tissue stain with a discussion of the principles involved. Anat Rec, 69, 31.
- Doğan BA, Karakılıç E, Tuna MM, et al. (2015): Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism. Clin Endocrinol, 82, 422-428.
- Hak AE, Westendorp IC, Pols HA, et al. (2007): High- dose testosterone is associated with atherosclerosis in postmenopausal women. Maturitas, 56, 153-160.
- Hanke H, Lenz C, Hess B, et al. (2001): Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall. Circulation, 103, 1382-1385.
- Hsu YJ, Dimke H, Schoeber JP, et al. (2010): Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins. Kidney Int, 77, 601-608.
- Iliescu R, Reckelhoff JF (2006): Testosterone and vascular reactivity. Clin Sci, 111, 251-252.
- Jesmin S, Hattori Y, Sakuma I, et al. (2003): Estrogen deprivation and replacement modulate cerebral capillary density with vascular expression of angiogenic molecules in middle-aged female rats. J Cereb Blood Flow Metab, 23, 181-189.
- Kearney ML, Hurn FPD (2004): Testosterone as a modulator of vascular behavior. Biol Res Nurs, 5, 276-285.
- Li S, Guo Y, Zhu P, Yang T (2013): Role of Ox-LDL/LOX- 1/NF-κB signaling pathway in regulation of atherosclerotic plaque growth by testosterone in male rabbits. Vascul Pharmacol, 59, 131-137.
- Mathur A, Malkin C, Saeed B, et al. (2009): Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. Eur J Endocrinol, 161, 443- 449.
- O’Connor EK, Ivey JR, Bowles DK (2012): Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine. Biol Sex Differ, 3, 10.
- Otrock ZK, Mahfouz RAR, Makarem JA, et al. (2007): Understanding the biology of angiogenesis: Review of the most important molecular mechanisms. Blood Cells Mol Dis, 39, 212-220.
- Saad F (2012): Androgen therapy in men with testosterone deficiency: Can testosterone reduce the risk of cardiovascular disease? Diabetes Metab Res Rev, 28, 52- 59.
- Shidaifat F, Gharaibeh M, Bani-Ismail Z (2007): Effect of castration on extracellular matrix remodeling and angiogenesis of the prostate gland. Endocr J, 54, 521-529.
- Sieveking DP, Lim P, Chow RWY, et al. (2010): A sex- specific role for androgens in angiogenesis. J Exp Med, 207, 345-352.
- Soisson V, Brailly-Tabard S, Empana JP, et al. (2012): Low plasma testosterone and elevated carotid intima-media thickness: Importance of low-grade inflammation in elderly men. Atherosclerosis, 223, 244-249.
- Sordello S, Bertrand N, Plouet J (1998): Vascular endothelial growth factor is up-regulated in vitro and in vivo by androgens. Biochem Biophys Res Commun, 251, 287-290.
- Tsujimura A, Yamamoto R, Okuda H, et al. (2012): Low serum free testosterone level is associated with carotid intima-media thickness in middle-aged Japanese men. Endocr J, 59, 809-815.
- Wang W, Chao S, Xian W (2002): Alteration of vascular response to norepinephrine, calcitonin gene-related peptide, and acetylcholine in orchidectomized rats. Acta Pharm Sinic, 23, 985-990.
- Yıldız O (2007): Vascular smooth muscle and endothelial functions in aging. Ann N Y Acad Sci, 1100, 353-360. Geliş tarihi: 05.01.2016 / Kabul tarihi: 12.04.2017 Address for correspondence: Prof. Dr. İlknur DABANOĞLU Adnan Menderes University, Faculty of Veterinary Medicine, Department of Anatomy Işıklı Köyü 09016 Aydın, Turkey. Tel: + 90 256 247 0700-242 e-mail: dabanf@yahoo.com
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Veteriner Cerrahi |
| Diğer ID | JA69MP62HY |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Eylül 2017 |
| Yayımlandığı Sayı | Yıl 2017 |