Diet-Induced Obesity and Ghrelin Effects on Pituitary Gonadotrophs: Immunohistomorphometric Study in Male Rats

The close relationship between energy metabolism, nutritional state, nd eproductive physiology suggests that nutritional and metabolic disorders can disrupt ormal reproductive function and fertility. Considering the importance of leptin and hrelin effects in regulation of the hypothalamic-pituitary-gonadal axis, the objective f this study was to investigate the influence of obesity and centrally applied ghrelin n immunohistochemical appearance and quantitative morphology of the pituitary ollicle-stimulating hormone (FSH) and luteinizing hormone (LH) producing cells in dult male rats. In this experimental study, animals were given two ifferent iets: normal-fat (NF) and high-fat (HF), for 4 weeks, corresponding to normal nd positive energy balance (n=2×14), respectively. Each group was subsequently ivided into two subgroups (n=7) receiving intracerebroventricular (ICV) injections of ither ghrelin [G, 1 μg/5 μL phosphate buffered saline (PBS)] or vehicle (5 μL PBS, ontrol group) every 24 hours for five consecutive days. Morphometric analyses showed that in HF control group, the ercentage of SH cells per unit volume of total pituitary gland tissue (in μm3), i.e. volume density Vvc), was increased (P<0.05) by 9.1% in comparison with the NF controls. After CV treatment with ghrelin, volume (Vc) and volume density (Vvc) of FSH cells in hrelin+NF (GNF) and ghrelin+HF (GHF) groups remained unchanged in comparison ith NF and HF controls. Volume of LH cells in HF control group was increased by 7% (P<0.05), but their Vvc was decreased by 8.3% (P<0.05) in comparison with F controls. In GNF group, the volume of LH cells increased by 7% (P<0.05), in omparison with the NF controls, but in GHF group, the same parameter remained nchanged when compared with HF controls. The central application of ghrelin ecreased he Vvc of LH cells only in GNF group by 38.9% (P<0.05) in comparison with he NF control animals. The present study has shown that obesity and repetitive ICV dministration f low doses of ghrelin, in NF and HF rats, modulated the immunohistomorphometric eatures of gonadotrophs, indicating the importance of obesity and ghrelin in regulation f he reproductive function.