Gonadal Hormones and Gonadal Function in Type 2 Diabetes Model OLETF (Otsuka Long Evans Tokushima Fatty) Rats

Abstract

Abstract. Gonadal functions, with special reference to blood levels of sex-related markers such as 17b-estradiol (E2), free testosterone (free Te) and lutenizing hormone (LH), were examined in male OLETF (Otsuka Long Evans Tokushima Fatty) diabetic rats, a model of human type 2 diabetes mellitus. Male rats of the OLETF strain and male rats of the LETO strain, which act as a control of OLETF, both supplied by Otsuka Pharmaceutical Co., Ltd. (Tokushima, Japan), were periodically examined for blood levels of E2, free Te and LH at the age of 4, 5, 32, 40 and 64 weeks. The weight of the testis, the number of sperm contained within and histological findings of the testis were comparatively studied in both strains. Glucose and insulin (IRI) at fasting were examined to evaluate the homeostasis model assessment (HOMA) index. In order to investigate any sex hormone imbalance, sex hormone-binding globulin (SHBG) was measured by a dextrancharcoal assay. All of the OLETF rats became diabetic at the age of 32 weeks. There were no significant differences between OLETF and LETO rats regarding free Te, E2, LH or SHBG during the observation period from 4 to 64 weeks. Testis weight was significantly decreased in OLETF rats at 32 and 64 weeks and sperm counts at 64 weeks of age were also significantly decreased. Histologically, there was seminiferous tubule atrophy in the OLETF rats at 64 weeks of age. A significant negative correlation between testis weight and fasting blood glucose, as well as HOMA index, was observed in OLETF rats. In male diabetic OLETF rats, with a variety of hypogonadisms such as atrophy of the testis and low sperm count, the serum levels of E2, free Te, LH and SHBG were normally preserved. [5,6]. From about 20 weeks of age, OLETF rats begin to develop diabetes accompanied by obesity, and almost all of the rats develop diabetes by the age of 30 weeks. This study was intended to make clear, whether sexual dysfunctions, if any, occur in diabetic OLETF rats by examining serum levels of sex-related hormones and sex hormone-binding globulin (SHBG), as well as testis findings. SHBG is a factor affecting sex hormone activities by binding both testosterone and 17b-estradiol (E2), with a higher affinity for the former [7,8]. Materials and Methods AnimalsBoth OLETF rats and their controls, named LETO (Long-Evans Tokushima Otsuka) rats, which are nondiabetic, were supplied by Otsuka Pharmaceutical Co., Ltd. (Tokushima, Japan). OLETF rats comprising 4, 5, 32, 40 and 64 weeks of age and control LETO rats corresponding to each OLETF age were studied. After

Diabetic Complications in Obese Type 2 Diabetic Rat Models

“…In OLETF rats, biochemical parameter levels, such as free testosterone, 17β-estradiol, LH, and sex hormone-binding globulin (SHBG), were not changed from 4 to 64 weeks of age, as compared with lean rats [43]. Testis weight was decreased in OLETF rats at 32 and 64 weeks of age, and the sperm counts at 64 weeks of age were also decreased as compared with lean rats.…”

Gender Differences in Metabolic Disorders and Related Diseases in Spontaneously Diabetic Torii-LeprfaRats

“…Streptozotocin- (STZ-) induced diabetic rats showed a significant decrease in serum testosterone levels [16]; however, serum testosterone levels in Otsuka Long-Evans Tokushima fatty (OLETF) rats were comparable to those in control rats [17]. In obese males, total testosterone, free testosterone, and sex hormone-binding globulin (SHBG) levels were all commonly decreased [18, 19].…”

“…In sperm morphological analyses, the percentage of normal spermatozoa in SDT fatty rats was significantly decreased at 40 weeks of age, as compared with that in SD rats. In OLETF rats, the sperm count decreased significantly at 64 weeks of age, in comparison to control rats [17]. In humans, total sperm count and total motile sperm are negatively correlated with weight, waist circumference, and hip circumference, suggesting a potential link between obesity, hypogonadism, and infertility as indicated by semen analyses [22].…”

“…In the testes of STZ-induced diabetic mice, ultrastructural changes, such as an increase in lipid droplets and a decrease in smooth endoplasmic reticulum, were observed in Leydig cells [23]. A tendency toward seminiferous tubular atrophy has been reported in 64-week-old OLETF rats; however, structures for interstitial tissues including Leydig cells remained conserved [17]. No histological abnormalities were observed in testes or epididymis in SDT fatty rats, and the reason for hypotestosteronemia or sperm abnormalities should be elucidated in further studies.…”

A decrease of sensitivity of adenylyl cyclase and heterotrimeric g-proteins to chorionic gonadotropin and peptide hormones action in the tissues of reproductive system of the rats in the condition of experimental type 2 diabetes

“…Вероятно, со снижением чувствительности АЦС к гонадотропинам связан и широкий спектр нарушений контролируемых этими гормонами функций репродуктивной системы как у людей, страдающих диабетом 1-го и 2-го типа, так и у крыс с различными экспериментальными моделями диабета [22,23]. Наиболее частыми среди них являются нарушения процессов сперматогенеза и фолликулогенеза, которые сопровождаются изменением содержания стероидных гормонов и их предшественников, синтез которых контролируется гонадотропинами через посредство cAMP-зависимых сигнальных каскадов [24].…”