Lemini M, Ruiz-Herrera X, Ledesma-Colunga MG, Díaz- Lezama N, De los Ríos EA, López-Barrera F, Méndez I, Martínez de la Escalera G, Macotela Y, Clapp C. Prolactin anterior pituitary expression and circulating levels are reduced in obese and diabetic rats: role of TGF-b and TNF-α. Am J Physiol Regul Integr Comp Physiol 308: R792–R799, 2015. First published February 25, 2015; doi:10.1152/ajpregu.00327.2014.—The levels of the hormone prolactin (PRL) are reduced in the circulation of patients with Type 2 diabetes and in obese children, and lower systemic PRL levels correlate with an increased prevalence of diabetes and a higher risk of metabolic syndrome. The secretion of anterior pituitary (AP) PRL in metabolic diseases may be influenced by the interplay between transforming growth factor b (TGF-b) and tumor necrosis factor α (TNF-α), which inhibit and can stimulate AP PRL synthesis, respectively, and are known contributors to insulin resistance and metabolic complications. Here, we show that TGF-b and TNF-α antagonize the effect of each other on the expression and release of PRL by the GH4C1 lactotrope cell line. The levels of AP mRNA and circulating PRL decrease in high-fat diet-induced obese rats in parallel with increased and reduced AP levels of TGF-b and TNF-α mRNA, respectively. Likewise, AP expression and circulating levels of PRL are reduced in streptozotocin-induced diabetic rats and are associated with higher AP expression and protein levels of TGF-b and TNF-α. The opposing effects of the two cytokines on cultured AP cells, together with their altered expression in the AP of obese and diabetic rats suggest they are linked to the reduced PRL production and secretion characteristics of metabolic diseases.