Recently it has been found that testosterone can maintain and restimulate serum and pituitary follicle-stimulating hormone (FSH) in the gonadotropin-releasing hormone (GnRH) antagonist treated adult male rat. The present investigation was undertaken to determine (1) which metabolite of testosterone, dihydrotestosterone (DHT), or estradiol accounts for the effects of testosterone in GnRH antagonist suppressed rats and (2) whether these effects of testosterone are influenced by other testicular factors. Eight groups of 6–8 adult male Sprague-Dawley rats were subjected to the following treatments: vehicle, GnRH antagonist (75 µg/day s.c), testosterone-filled Silastic implants (3 × 5 cm, s.c), DHT-filled Silastic implants (3 × 5 cm, s.c), estradiol ben-zoate (15 µg/day s.c), and combined administration of GnRH antagonist with either steroid. In addition, the GnRH antagonist/ testosterone treatment regimen was applied to rats orchidectomized 72 h prior to initiation of treatments. After 3 weeks of treatment, serum was analyzed for concentrations of luteinizing-hormone (LH), FSH, testosterone, DHT, and estradiol. Pituitary extracts were analyzed for LH and FSH content. Except for the vehicle-treated groups, serum and pituitary LH concentrations were markedly suppressed by all treatments. In intact rats treated with GnRH antagonist alone and/or estradiol, the pituitary FSH level was reduced by more than 70% relative to controls, while both testosterone and DHT maintained pituitary FSH. Similarly, testosterone and DHT, but not estradiol, delayed the decline of serum FSH induced with GnRH antagonist alone. In orchidectomized animals, testosterone was also capable of preventing a reduction of pituitary FSH despite concomitant GnRH antagonist administration. It is concluded that testosterone and DHT selectively maintain FSH in the GnRH antagonist treated male rat. This paradoxical stimulation of FSH occurs in the absence of other testicular factors.
The effects of androgens on the bioactivity and molecular composition of pituitary FSH were examined in intact and GnRH antagonist-suppressed male rats. Eight groups of adult Sprague-Dawley rats were subjected to the following treatments: antagonist (75 \g=m\g/day by osmotic minipumps; sc), testosterone-filled Silastic implants (3\m=x\5cm, sc), dihydrotestosterone-filled Silastic implants (3\m=x\5cm, sc), E2 benzoate (15 \g=m\g/day,sc), and combined administration of antagonist with either steroid for 3 weeks. At the end of the treatment period, pituitaries were dissected out and homogenised. FSH content was determined in the pituitary extracts by an in vitro bioassay and a radioimmunoassay. Individual pituitary extracts from rats treated with vehicle, testosterone and testosterone + antagonist were subjected to isoelectric-focusing on sucrose density gradients performed in the pH range from 3.5 to 7.0. Individual isoelectric-focusing fractions (100-120) were analysed for bioactive and immunoreactive FSH. Treatment with antagonist, E2 or antagonist + E2 caused a significant decrease in pituitary FSH, whereas testosterone and dihydrotesterone alone or in combination with antagonist prevented the decrease in pituitary FSH. The effects of all treatments on both bioactive and immunoreactive FSH were similar. Testosterone treatment not only maintained FSH synthesis but also altered the molecular composition of pituitary FSH. Following treatment with testosterone there was a shift of maximal FSH bioactivity to the more acidic pH range. On the other hand, less bioactivity was recovered than corresponding immunoreactivity in the higher pH region, resulting in significantly reduced ratios of bioactivity to immunoreactivity of FSH. No significant differences were found in the isoelectric-focusing profiles or bioactivity to immunoreactivity ratios of pituitary FSH in animals treated with testosterone alone or in combination with antagonist. The results demonstrate that testosterone not only maintained the synthesis of both bioactive and immunoreactive FSH in male rats, but also influences the molecular composition of pituitary FSH. These effects of testosterone on pituitary FSH appear not to be mediated through hypothalamic GnRH.Follicle-stimulating hormone exists in multiple mo¬ lecular forms within the anterior pituitary gland of several animal species and man (1-5). These isoforms of FSH differ not only in charge properties (isoelectric point; pi) but also in receptor binding activity (6), circulating half-life (7) and in vitro bi¬ ological potency (8,9). Furthermore, the relative abundance of these isoforms in the pituitary is af¬ fected by the endocrine status of the animal, such as castration (4,10,11), pubertal development (12), and during different phases of the reproductive cycle in the female (13), suggesting that gonadal factors might be involved in the regulation of mo¬ lecular heterogeneity of FSH (2,5,6,14,15). It has previously been demonstrated in our lab¬ oratory that testosterone (T) administration to male...
Disruption of brain-expressed G protein-coupled receptor-10 (GPR10) causes obesity in animals. Here, we identify multiple rare variants in GPR10 in people with severe obesity and in normal weight controls. These variants impair ligand binding and G protein-dependent signalling in cells. Transgenic mice harbouring a loss of function GPR10 variant found in an individual with obesity, gain excessive weight due to decreased energy expenditure rather than increased food intake. This evidence supports a role for GPR10 in human energy homeostasis. Therapeutic targeting of GPR10 may represent an effective weight-loss strategy.
Background: Obesity, the new world syndrome is the major health problem pandemically. One of the causes of dyslipidemia is obesity. The study was aimed to detect the pattern and prevalence of dyslipidemia in obese persons.Methods: Case control study included 70 subjects categorized into two groups based on BMI (body mass index) as cases (obese) with BMI >25 kg/m2 (n=35) and controls (non-obese) with BMI <25 kg/m2 (n=35). Anthropometric measurements such as waist and hip circumference and waist to hip ratio were measured. Fasting venous blood samples collected were estimated for total cholesterol, triglycerides, high density lipoprotein. Non-HDL-cholesterol, atherogenic indices such as atherogenic index of plasma, Castelli's risk index I and II and atherogenic coefficient were calculated from the estimated lipids.Results: Dyslipidemia observed in obese cases was hypercholesterolemia, hypertriglyceridemia (28.57%), lowered HDL (57.14%) and increased LDL (65.71%). Significant lower HDL, elevated non-HDL cholesterol, CRI-I, II and AC were observed in cases compared to controls. BMI had a significant negative correlation with HDL and positive correlation with anthropometric measurements, TC, non-HDL cholesterol and atherogenic indices. TC and HDL were associated with all the atherogenic indices. CRI-I, CRI-II and AC have significant diagnostic utility, with CRI-I and AC having more sensitivity and specificity at cut off values of 3.85 and 2.85 respectively.Conclusions: Decrease in HDL, elevated non-HDL cholesterol and atherogenic indices are associated with BMI. CRI-I and AC are indicative cardiovascular risk.
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