ESPE Abstracts (2016) 86 P-P2-412

Towards the Roles of Kisspeptins in the Control of Gonadotropic Axis: Focus on Peripheral Signaling in Androgen-Dependent Tissues in the Experimentally Induced Model Hypogonadotropic Hypogonadism in Male Rats

Irina Nikitina, Yulia Khoduleva, Irina Nagornaya, Alekber Bairamov, Petr Shabanov & Alisa Masel

North-West Medical Research Centre named after Almazov, Saint-Petersburg, Russia

Background: Recently kisspeptins are considered as a key gatekeepers of the regulation of the gonadotropic axis.

Objective and hypotheses: To investigate the impact of experimentally induced hypogonadism on kisspeptins signaling in androgen-dependent tissues and blood.

Method: Wistar male rats (29 in total) were used. Rats were divided into four groups. Group 1 (control, prepubertal rats aged 2 months, n=7). Group 2 (control, pubertal rats aged 4 months, n=6). Group 3 (unilaterally gonadectomized (ULG) in neonatal period). Group 4 (ULG treated with testosterone (T) propionate 5 mg/kg per day for 10 days). In all groups the density of GPR54 in testes, muscle as well as serum kisspeptin and T levels were examined. The data was expressed as median values (Me) that were compared by Wilkokson criterion.

Results: Density of GPR54 in gonads in group 3 was lower than in group 2 (Me 0.88 ng/mg vs 1.13 ng/mg, P<0.05) and similar to group 1(Me 0.92 ng/mg). Unlike above, density of GPR54 in muscle in groups 1,2,3 there were not any differences (Me 0.1; 0.12; 0.13 ng/mg, P>0.05). Generally, density of GPR54 in group 2 in gonads was significantly higher than in the same group in muscle (Me 0.784 ng/mg vs 0.114 ng/mg, P<0.01). In the group 3 a significant decrease in serum levels of T (Me 15.39 ng/mg) in comparison with group 2 (Me 20.02 ng/mg, P<0.01) was detected. Serum levels of kisspeptins in both groups were the same (0.27 ng/mg and 0.26 ng/mg, P>0.05). Treatment with testosterone propionate of group 4 rats lead to increase of serum level of T (from 15.39 ng/mg to 26.26 ng/mg, P<0.01), but did not modify the density of GPR54 in gonads (Me 0.79 ng/mg).

Conclusions: Hypogonadism lead to decrease of kisspeptins signaling in peripheral androgen-dependent tissues. Serum level of kisspeptins is physiologically low and it probably can not be used as a marker of kisspeptin system activity. Testosterone treatment is not effective enough; new therapeutic methods are required.