homayoon khazali

It is well established that ghrelin has effect on gonadotropin and androgen release through its receptors on hypothalamus, pituitary and gonads. The amount of synthesis and release of these hormones directly affect on reproductive behavior in mammals. Therefore, it is expected that ghrelin can affect sexual behavior of mammals. The aim of the present study was to investigate the effects of intracerebroventricular injection of ghrelin on sexual behavior of male rat. Forty male Wistar rats, weighing 200±20 g, were divided into four groups. The animals received saline or 2, 4 or 8 nmol ghrelin through the stereotaxically implanted cannula into the third cerebral ventricle. The sexual behavior indices of male rats were evaluated encountering with female rats 10 min after injection of the ghrelin or saline. As well as the locomotor activity of male rats was investigated by open-field test. Then the experimental data were statistically analyzed by one-way analysis of variance (ANOVA) followed by Tukey’s test. Four and 8 nmol injection of ghrelin caused significant increase in the mount (p<0.05), intromission and ejaculation (p< 0.001) latency compared to the control group. Also the 4 and 8 nmol doses of ghrelin led to a significant increase in the number of mount (p<0.05) and a significant decrease in the number of ejaculation (p<0.001) compared to control animals. No significant changes were observed in the number of intromission after ghrelin injection. Comparison of sexual activity index and copulatory efficiency in the studied groups indicated a significant (p<0.05) decrease in reproductive activity of 4 and 8 nmol ghrelin-received animals compared to the control group. As well we observed a significant increase in locomotor activity of 2 nmol (p<0.01) and 4 and 8 nmol (p<0.001) ghrelin-received animals compared to control group. Intracerebroventricular injection of ghrelin suppressed the sexual behavior of male rats dose-dependently, whereas increased the locomotor activity.

Ghrelin exerts inhibitory effects on gonadotropins secretion. The product of TSPO gene is mainly found on the outer mitochondrial membrane and it is a key protein in the steroidogenesis pathway. It transports cholesterol in to mitochondria of organs that synthesize steroids. Treatment of neonatal female rats with testosterone propionate (TP) alters gonadotropin secretion patterns in the adulthood. In the present study the effects of central injection of ghrelin were investigated on the expression of TSPO gene in the ovaries of pubertal androgenized female rats.Twenty neonatal female rats were androgenized on the third day after birth by subcutaneous injection of 50µg TP and five neonatal female rats in one group was considered as controls. After puberty, the animals in four groups (n=5 in each group) received central injections of saline or different doses of ghrelin(2, 4 or 8µg). Also, five non-androgenied rats as control group received central injection of saline. The ovaries were removed bilaterally and frozen. TSPO gene expression levels was determined by semi quantitative RT-PCR.The mRNA levels of TSPO increased significantly in the ovaries of the androgenized rats compared to the controls. Ghrelin injections decreased significantly TSPO gene expression compared to the androgenized rats (P <0.05).Androgen may stimulate TSPO gene expression in the ovaries. Ghrelin may exert inhibitory effects on reproductive axis partly via reducing the expression of genes involved in the steroidogenesis.

Ghrelin, increases food intake, decreases T3 and T4 concentrations and stimulates insulin release, while leptin reduces food intake and suppresses appetite. Considering the importance of thyroid hormones, ghrelin and leptin in body metabolism, the purpose of this study was to investigate the effect of interactions between ghrelin and leptin (injected via ICV route) and plasma T3 and T4 concentrations in rats. Fifty-six Wistar male rats (230 to 250 g/BW) were randomly divided into 7 groups. Groups 1, 2 and 3 received 1, 3 and 5 nmol ghrelin, while groups 4, 5 and 6 received 1, 5, 10 nmol leptin (2 μl via lateral cerebral ventricle). Animals in the 7th group received 5 nmol ghrelin with 10 nmol leptin via the same route for 3 days. Blood samples were collected daily starting from one day before until one day after infusions and plasma samples were used to assess T3 and T4 concentrations by RIA. To ensure proper cannulation, perfusion and brain slices were performed. The results indicated that ghrelin significantly decreased T3 and T4 concentrations, whereas leptin increased these concentrations. The simultaneous injection of ghrelin and leptin significantly reduced the inhibitory effect of ghrelin on thyroid hormones concentrations. According to the results and other researchers’ suggestions, the opposite effects of leptin and ghrelin could be emphasized and some hormonal mechanisms for these 2 hormones (transmitters) such as HPA and/or HPT axes or MSH systems could be suggested.

ghrelin is a potent orexigenic agent in rodents and humans. Some studies have shown that ghrelin participates in the adaptive response to weight loss and plasma concentration of ghrelin rises with dieting. On the other hand, weight loss and fasting is accompanied by increased levels of epinephrine and cortisol. In this study, we investigated the effects of epinephrine and cortisol on fasting-induced ghrelin secretion in rats fed different levels of their energy requirements. forty five male Wistar rats (300-350 g, 15 per group) were fed a diet containing 100%, 50% and 25% of their energy requirement for 10 days followed by 2 days of fasting. Animals were then anesthetized for carotid artery cannulation, which was used for injections and blood samplings. Rats received either 3 μg epinephrine (Ep)/Kg BW, 3 μg cortisol (Cor)/Kg BW, or a combination of these two (0.1 mg in 1 ml of PBS). Blood samples were collected before injections and 30, 60, and 120 min after injections. mean plasma concentration of baseline ghrelin increased in the animals fed 50% food restriction (P≤0.01). In 100% and 50% food restricted groups, fasting ghrelin levels fell after epinephrine and combination of epinephrine and cortisol injection (P≤0.05). In contrast, the group that had 25% food restriction did not show any response to epinephrine and combination of epinephrine and cortisol (P>0.05), while the levels of the fasting ghrelin rose significantly after cortisol treatment (P≤0.01). These results indicate that injection of epinephrine suppresses starvation-induced secretion of ghrelin in normal (100%) and starved (50%) rats. Ghrelin secretion response to epinephrine might be affected by weight loss as it does not seem to be suppressed in starved (25%) rats.

The aim of this study was to determine changes in the concentration of leptin and thyroid hormone in energyrestricted ewes and effect of leptin injection on thyroid hormone level. In the first experiment, 28 ewes were assigned to two groups(n=14). Ewes were fed by a ration that provided 60% or 100% of maintenance energy requirements during 71 days. Blood samples were collected and body weight(BW) and body condition score(BCS) were determined. In the second experiment, 6 energy-restricted ewes from the first experiment were selected and assigned to two groups(n=3). Ewes were fed a ration that provided 60% of maintenance energy requirements and injected by 1 or 4 Kg leptin/Kg BW.Blood samples were taken and BW and BCS were determined. In the first experiment, concentrations of leptin, T3 and T4, BW and BCS were decreased in energyrestricted ewes(p<0.01). In the second experiment,concentration of T3, T4 and leptin were increased by leptin injection(p<0.01). The results suggested leptin injection may restore thyroid hormone secretion to normal levels in energy-restricted ewes.