OBJECTIVES: We explored the possible preventive/therapeutic effects of orlistat (a medication prescribed for weight loss) on obesity-induced steroidogenesis and spermatogenesis decline.
MATERIALS AND METHODS: Twenty-four adult male Sprague Dawley rats weighing 250-300 g were randomized into four groups (n = 6/group), namely; normal control, high-fat diet, high-fat diet plus orlistat preventive group and high-fat diet plus orlistat treatment group. Orlistat (10 mg/kg/b.w./d suspended in distilled water) was either concurrently administered with high-fat diet for 12 weeks (high-fat diet plus orlistat preventive group) or administered from week 7-12 post- high-fat diet feeding (high-fat diet plus orlistat treatment group). Thereafter, serum, testes and epididymis were collected for analyses.
RESULTS: Obesity increased serum leptin and decreased adiponectin levels, decreased serum and intra-testicular levels of follicle stimulating hormone, luteinising hormone and testosterone, sperm count, motility, viability, normal morphology and epididymal antioxidants, but increased epididymal malondialdehyde level and sperm nDNA fragmentation. Testicular mRNA transcript levels of androgen receptor, luteinizing hormone receptor, steroidogenic acute regulatory protein, cytochrome P450 enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were significantly decreased in the testes of the high-fat diet group. Further, the levels of steroidogenic acute regulatory protein protein and enzymatic activities of CYP11A1, 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were also significantly decreased in the testes of the high-fat diet group. Treatment with orlistat significantly decreased leptin and increased adiponectin levels, improved sperm parameters, decreased sperm DNA fragmentation, increased the levels of steroidogenic hormones, proteins and associated genes in high-fat diet-induced obese male rats, with the preventive group (high-fat diet plus orlistat preventive group) having better results relative to the treatment group (high-fat diet plus orlistat treatment group).
DISCUSSION AND CONCLUSION: Orlistat attenuated impaired spermatogenesis and steroidogenesis decline by up-regulating steroidogenic genes. This may not be unconnected to its significant effect in lowering serum leptin levels, since the hormone is known to dampen fertility potential. Therefore, orlistat may improve fertility potential in overweight/obese men.
METHODS: Forty-eight Sprague Dawley rats were randomly divided into six groups of eight rats each: (A) Sham operated; control (B) Untreated (ovariectomised (OVX) with vehicle), (C) PEL 100 (OVX + 100 mg/kg body weight (bw)), (D) PEL 300 (OVX + 300 mg/kg bw), (E) PEL 500 (OVX + 500 mg/kg bw) and (F) Positive control, testosterone undecanoate (TU) (OVX+ 10 mg/kg bw). Group A and B received daily oral administrations of the vehicle, Group C-E received daily oral administration of PEL and Group F received testosterone undecanoate intramuscularly weekly. At the end of 8 weeks, serum calcium, phosphate, bone alkaline phosphatase (BALP), osteocalcin, follicle stimulating hormone (FSH), luteinising hormone (LH), oestrogen, progesterone and testosterone were measured, then the animals were sacrificed and uterus was isolated, while weight was recorded in all experimental groups.
RESULTS: Treatment of OVX rats with PEL at a dose of 500 mg/kg showed decreased serum FSH (P
METHODS: Two rat models were used: (i) ovariectomised, sex-steroid replaced and (ii) intact, at different phases of oestrous cycle. A day after completion of sex-steroid treatment or following identification of oestrous cycle phases, rats were sacrificed and expression and distribution of these proteins in uterus were identified by Western blotting and immunohistochemistry, respectively.
RESULTS: Expression of TRα-1, TRβ-1, TSHR, VDR, RAR and ERK1/2 in uterus was higher following estradiol (E2) treatment and at estrus phase of oestrous cycle when E2levels were high. A relatively lower expression was observed following progesterone (P) treatment and at diestrus phases of oestrous cycle when P levels were high. Under E2influence, TRα, TRβ, TSHR, VDR, RAR and ERK1/2 were distributed in luminal and glandular epithelia while under P influence, TSHR, VDR abn RAR were distributed in the stroma.
CONCLUSIONS: Differential expression and distribution of TRα-1, TRβ-1, TSHR, VDR, RAR and ERK1/2 in different uterine compartments could explain differential action of thyroid hormone, TSH, vitamin D, and retinoic acid in uterus under different sex-steroid conditions.
MATERIALS AND METHODS: Ovariectomized adult female rats were given testosterone (1 mg/kg/day) alone or in combination with flutamide or finasteride between days 6 to 8 of sex-steroid replacement treatment, which was considered the period of uterine receptivity. Ultramorphology of tight junctions was visualized by transmission electron microscopy while distribution and expression of claudin-4 and occludin were examined by immunofluorescence and real-time polymerase chain reaction respectively.
RESULTS: Administration of testosterone caused loss of tight junction complexity and down-regulated expression of claudin-4 and occludin in the uterus.
CONCLUSION: Decreased endometrial tight junction complexity and expression of claudin-4 and occludin in the uterus during receptivity period by testosterone may interfere with embryo attachment and subsequent implantation.
METHODS: Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 μg/kg), progesterone (4mg) and testosterone (125 & 250μg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively.
RESULTS: RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms.
DISCUSSION: Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee.
CONCLUSION: Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male.
METHODS: The whole study was carried out on 48 adult Wistar rats (24 male: 12 obese and 12 lean and 24 female: 12 obese and 12 lean). Each male and female rat group was further subdivided into two groups (n = 6/group) and treated with normal saline/tramadol for 5 days. On the fifth day, 15 min after tramadol/normal saline treatment, animals were tested for pain perception toward noxious stimuli. Later, endogenous 17 beta-estradiol and free testosterone levels in serum were estimated through ELISA methods.
RESULTS: The present study revealed that female rats experienced more pain sensitivity to noxious stimuli compared to male rats. High-fat diet-induced obese rats experienced more pain sensations to noxious stimuli than lean rats. Obese male rats were found to have significantly low free testosterone and high 17 beta-estradiol levels compared to lean male rats. An increase in serum 17 beta-estradiol level led to increased pain sensation to noxious stimuli. While an increase in free testosterone level resulted in the lowering of pain sensation to noxious stimuli.
CONCLUSION: The analgesic effect of tramadol was more pronounced in male rats compared to female rats. The analgesic effect of tramadol was more marked in lean rats compared to obese rats. Additional research to elucidate obesity-induced endocrine changes and the mechanisms driving sex hormones in pain perception is needed to foster future interventions to reduce disparities in pain.