GENDER DIFFERENCES IN ERβ EXPRESSION AND PITUITARY CELL RESPONSE TO DEHP PERINATAL TREATMENT

PABLO A. PÉREZ; JONATHAN TOLEDO; FLORENCIA PICECH; JUAN P. PETITI; AL TORRES; ANA L. DE PAUL; SILVINA GUTIÉRREZ

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Congreso; Reunión Anual de Sociedades de Biociencia 2020; 2020

Sociedad Argentina de Investigación Clínica

Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate, non-covalently bounded to PVC polymers, acting as en-docrine disruptor by interfering with estrogen signaling. One of the most relevant targets of E2 actions is the pituitary gland, whose en-docrine populations expresses receptors (ER) and is sensitive to E2 variations. The aim of this study was to analyze the effect and gender differences of perinatal DEHP exposure on pituitary ERβ ex-pression, exploring the impact on lactotroph cell growth. Female Wistar rats were exposed to DEHP (200mg/kg) or corn oil (controls) by gavage from day 0 of gestation, throughout pregnan-cy and lactation, until weaning. Male and female pups were used at 21 (prepubertal) and 75 (adult) postnatal (PND) days. Also, pi-tuitary cultures from male and female rats were stimulated for 72h with 1, 10 or 100 nM of DEHP. The ERβ+ cells were determined by flow cytometry and the lactotroph (ki67+) were quantified by double immunostaining. The statistical analysis used was ANOVA Fisher (P<0.05).Perinatal DEHP increased ERβ expression in prepuberal and adult male rats. However, in female rats while DEHP also increased ERβ expression in prepubertal rats, the ERβ decreased in adulthood. In vitro system, all tested doses of DEHP up regulated the ERβ+ cells in cultures from male, with opposite effects in female cultures, showing ERβ decrease in a dose-dependent manner. Also, DEHP reduced the lactotroph Ki67+ cells in male, with contrary effect in female rats showing that DEHP increased lactotroph Ki67+ cells. These results showed that DEHP exposition during embryogenesis and perinatal development induces changes in the pituitary gland, with differential effect on ERβ expression in male and female rats and lactotroph cell growth. These changes in ER expression may be a mechanism underlying DEHP exposure in the pituitary gland, leading to cell growth deregulation.