Disruption of hypothalamic control of food intake in phytoestrogen deprived animals is associated with changes in de novo synthesis of neurosteroids

ANDREOLI MF; STOKER C; LAZZARINO GP; PADUÁN B; RAMOS JG

Workshop; IWNE 2015; 2015

Objectives: withdrawal of dietary phytoestrogens induces obesity and increases energy intake upregulating orexigenic and downregulating anorexigenic neuropeptides. These effects may be exerted through phytoestrogen binding to estrogen receptor alpha (ER). Steroids regulate food intake: estradiol is anorexigenic, while progestagens [progesterone (Pg) and allopregnanolone (Allo)] are orexigenic. We hypothesize that disruption of hypothalamic food intake control in phytoestrogen-deprived animals may relate to changes in de novo synthesis of neurosteroids in this nucleus. Therefore, we aimed to study the effect of phytoestrogen withdrawal on hypothalamic expression of steroidogenic enzymesMethods and Results: Male rats fed from conception to adulthood with high-phytoestrogen (HP) diet were fed low-phytoestrogen diet (LP), high phytoestrogen?high fat obesogenic diet (HP-HF) or remained on HP diet for 15 weeks. Hypothalamic mRNA expression of steroidogenic enzymes and proteins [steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome P450 17α-hydroxylase (P450-17α), 3a-hydroxysteroid dehydrogenase (3-HSD), P450aromatase (ARO) and 5α-reductase-1 (5R)], ER, androgen (AR) and progesterone (PR) receptors, and relative activity of ER promoters (OS, O, OT, and E1) were quantified by real time PCR. Serum testosterone and estradiol were assessedP450scc and P450-17α expression was not detectable; 3β-HSD and ARO were increased by LP diet (p