Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats

Abstract

Hormone replacement therapy (HRT) has been used for several decades to treat menopausal discomforts. However, in the light of recent studies that draw attention to the potential hazards of conventional HRT, various attempts have been undertaken to search for alternatives to classical HRT. Phytoestrogens are claimed to be capable of positively influencing menopausal symptoms, including hot flushes. We designed a long-term study of 3 months to assess the effects of subcutaneous and orally fed 17 -estradiol (E2), as well as the actions of resveratrol (RES) on pituitary function in female rats. Our results have demonstrated that RES binds with a 10-fold lower affinity to estrogen receptor (ER)-than to ER . The data from the in vivo study revealed that a dosage of 5 µg and 50 µg RES/kg bodyweight per day given to ovariectomized (OVX) rats achieved serum levels of 1·0 and 8·1 µM respectively. Long-term treatment of OVX rats with RES revealed no estrogenic potential on pituitary function in vivo as assessed by LH and prolactin secretion and by regulation of mRNAs for LH , LH , and GnRH receptor. Subcutaneous treatment with E2 in silastic capsules exerted stronger effects on LH and prolactin secretion, as well as on LH , LH , GnRH receptor, and ER mRNA regulation compared with orally applied estradiol benzoate despite comparable serum levels. Levels of aryl hydrocarbon receptor (AhR) mRNA in the pituitary were increased following OVX and attenuated by longterm E2 treatment, whereas RES did not modulate AhR mRNA expression.

Resveratrol alters human endothelial cells redox state and causes mitochondrial-dependent cell death

“…In particular, our data showing the involvement of CYP2C9 suggest that ECs with a low oxidative condition may recognize resveratrol, in high concentration, as a dangerous compound rather than as an antioxidant, metabolizing it through anti-xenobiotic enzymes, thus producing ROS. While organs and tissue levels of resveratrol in humans is so far unknown, multiple evidence indicates that in rodents, resveratrol can accumulate in specific compartments such as heart, liver, and kidney at a concentration higher than in plasma (Bertelli et al, 1996;Bottner et al, 2006;Sale et al, 2004;Vitrac et al, 2003) and comparable to the ones we used in vitro, suggesting our results could be representative of a relevant in vivo mechanism.…”

The Response of Creatine Kinase Specific Activity in Rat Pituitary to Estrogenic Compounds and Vitamin D Less-Calcemic Analogs

“…This is in accordance with other studies clearly demonstrating that the pituitary is influenced by E 2 in both immature and Ovx rats, when other biological responses such as hormonal secretion were determined [3]. This is similar to other studies demonstrating the presence of ERs in the rat pituitary, which are responding to E 2 as well as to phytoestrogens like revestranol [3].…”

“…The pituitary expresses both estrogen receptors, ER α and ER β [2], and it responds to both ER α specific and ER β specific agonists [33]. E 2 was found to have pleiotropic effects on physiological function in rat pituitary [3]. …”

Grape Polyphenols Inhibit Akt/Mammalian Target of Rapamycin Signaling and Potentiate the Effects of Gefitinib in Breast Cancer

“…Our studies are unique in using an equimolar combination of resveratrol, quercetin, and catechin (RQC) at low concentrations within the range of 0.1-10 μM that may be accumulated in the circulation following consumption of grape products (15;18;55;56). However, caution must be used with interpretation of in vitro data because the compounds that were added to the tissue culture cells are relatively stable in their aglycone forms compared to the dietary polyphenols that are conjugated to glucoronic acid and sulfate during metabolism (19-21).…”