Relationships between leptin, the KiSS-1/GPR54 system and thyrotropic axis activity in ewe lambs predisposed to the delayed puberty

- The onset of puberty in ewe lambs is dependent on mother's body mass and birth type.
- Elevation in leptin concentration is connected with the onset of puberty in sheep.
- Kisspeptin concentration and expression rises during the onset of puberty in ewes.
- Pituitary GPR54 expression decreases at the time of the first ovulation in ewe lambs.
- Thyroid gland activity increases around the time of the first ovulation in ewes.

In the present study we compared body weight gains, some factors involved in the initiation of sexual maturation (pituitary expression of KiSS-1 and G protein-coupled receptors (GPR54), plasma concentrations of kisspeptin-10 (KiSS-10), leptin, thyroid-stimulating hormone (TSH), free thyroxin (fT4)) and the time of the first ovulation in ewe lambs predisposed to delayed puberty and control animals. The experiment was carried out on 114 ewes and 64 female lambs divided according to their birth type and body weight of their mothers. All ewe lambs were weighed at birth and every two weeks thereafter, until eight months of postnatal age. From four to eight months of postnatal age at monthly intervals, blood samples were collected from the jugular vein of all ewe lambs. Then, daily weight gains were recorded and plasma KiSS-10, leptin, TSH and fT4 concentrations were analysed by ELISA using species-specific antibodies. Starting from six months of age, the pituitary expression of KiSS-1/GPR54 mRNA was determined by Real Time-PCR. The activity of the ovaries was estimated using laparoscopy. The results obtained showed that the time of the onset of puberty in the ewe lambs depended on the mother's body mass, the plasma leptin level, and the birth type (singleton/twin). It was observed that the elevation of leptin concentration up to 3.35 ± 0.26-3.60 ± 0.19 ng/mL was associated with the initiation of puberty. Conversely, the hyperphysiological leptin levels found in ewe lambs, which were twin offspring of fatty sheep, were correlated with puberty delayed until the age of ten months. Moreover, it was found that a significant increase in pituitary KiSS-1 mRNA expression (1.40 ± 0.12-1.63 ± 0.22) (relative KiSS-1 mRNA expression level, ratio of KiSS-1 mRNA/GAPDH mRNA) and plasma KiSS-10 concentration (31.26 ± 1.54 ng/mL-32.24 ± 2.25 ng/mL) was connected with the occurrence of the first ovulation. On the other hand, GPR54 mRNA expression in the pituitary decreased around the time of the first ovulation. Also, the increase in thyroid gland activity was dependent on the mother's body mass as well as birth type and occurred around the time of the first ovulation.