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The indirect mechanism involves leptin action in pro\u2010opiomelanocortin (POMC)\u2010 and agouti\u2010related peptide (AgRP)\u2010expressing neurones. These cells innervate the paraventricular nucleus of the hypothalamus (PVH) where they modulate hypophysiotrophic thyrotrophin\u2010releasing hormone (TRH)\u2010producing neurones. The direct mechanism involves the expression of leptin receptor (LepR) in a subpopulation of PVH TRH neurones. However, to our knowledge, the existence of LepR in PVH TRH neurones of mice has not been clearly confirmed. Therefore, we investigated possible species\u2010specific differences between rats and mice with respect to the mechanisms recruited by leptin to regulate the HPT axis. We observed that an acute leptin injection induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin\u2010responsive cells, in 46.2\u00a0\u00b1\u00a08.0% of PVH proTRH immunoreactive neurones in rats. By contrast, an insignificant number of proTRH positive neurones in the mouse PVH co\u2010expressed leptin\u2010induced pSTAT3 or LepR. Similarly, central leptin injection increased the percentage of PVH proTRH neurones containing cAMP response element\u2010binding protein phosphorylation in rats, but not in mice. We investigated the innervation of AgRP and POMC axons in the PVH and observed that rats exhibited a denser POMC innervation in the PVH compared to mice, whereas rats and mice showed similar density of AgRP axons in the PVH. In conclusion, rats and mice exhibit important species\u2010specific differences in the direct and indirect mechanisms used by leptin to regulate the HPT axis.<\/jats:p>","DOI":"10.1111\/jne.12895","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T12:58:10Z","timestamp":1595854690000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic\u2010pituitary\u2010thyroid axis"],"prefix":"10.1111","volume":"32","author":[{"given":"Ana M.P.","family":"Campos","sequence":"first","affiliation":[{"name":"Departamento de Fisiologia e Biof\u00edsica Universidade de Sao Paulo Instituto de Ciencias Biomedicas Sao Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pryscila 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