Endocrine Abstracts

It is well established that the kisspeptins are the main activators of GnRH neurons and therefore essential for the onset of puberty and reproduction. Previous studies have suggested that kisspeptin neurons are possibly major targets of pro-inflammatory cytokines to regulate reproduction. SOCS (suppressor of cytokine signaling) are proteins that regulate, as it says, cytokines. They inhibit the transduction of intracellular effects caused by those molecules, once that cytokines recruit multiple intracellular signaling pathways that can induce either acute or long lasting/genomic responses in several tissues. Among the different SOCS proteins, SOCS3 plays a major role regulating the sensitivity of pro-inflammatory cytokines. Considering that Kiss1 mRNA coding is also found in other tissues besides the brain-related reproductive areas, the goal of the present study was to evaluate whether Socs3 inactivation in kisspeptin cells may modulate the development and metabolism of mice. We bred the Kiss1-Cre strain with mice carrying loxP-flanked Socs3 alleles. Mice carrying the kisspeptin-specific deletion were homozygous for the loxP-flanked Socs3 allele and hemizygous for the Kiss1-Cre transgene (Kiss1 SOCS3 KO), whereas their control group was composed of animals containing a homozygous loxP-flanked Socs3 allele. Sexual maturation was evaluated daily by determining the age of balano-preputial separation and by the age at vaginal opening, the first occurrence of vaginal cornification in the vaginal lavage (first estrus) and the first occurrence of an estrus cycle of normal duration. Body weight was recorded weekly and at every event of sexual maturation observed. Adult mice were submitted to glucose and insulin tolerance test or to a lipopolysaccharide S (LPS) acute injection. The adult animals were euthanized and adipose fat pad was collected. We observed that the sexual maturation of mice was not affected by specific Socs3 inactivation. No significant differences in body weight during development or adipose fat pads weight at adult age were observed between groups. Glucose and insulin sensitivity were similar between Kiss1 SOCS3 KO and control mice. Additionally, by using a model of acute inflammation we observed that specific Socs3 inactivation did not modulate the anorectic effects of inflammation induced by LPS. Our results demonstrated that Socs3 inactivation in Kiss1-expressing cells, does not affect the development of mice. Suggesting that the previous observed role of the kisspeptin neurons as targets of pro-inflammatory cytokines may be indirect or depend on other signaling pathway not assed in the present work.