Hypothalamic Expression of Neuropeptide Y (NPY) and Pro-OpioMelanoCortin (POMC) in Adult Male Mice Is Affected by Chronic Exposure to Endocrine Disruptors

Abstract

In the arcuate nucleus, neuropeptide Y (NPY) neurons, increase food intake and decrease energy expenditure, and control the activity of pro-opiomelanocortin (POMC) neurons, that decrease food intake and increase energy expenditure. Both systems project to other hypothalamic nuclei such as the paraventricular and dorsomedial hypothalamic nuclei. Endocrine disrupting chemicals (EDCs) are environmental contaminants that alter the endocrine system causing adverse health effects in an intact organism or its progeny. We investigated the effects of long-term exposure to some EDCs on the hypothalamic NPY and POMC systems of adult male mice that had been previously demonstrated to be a target of some of these EDCs after short-term exposure. Animals were chronically fed for four months with a phytoestrogen-free diet containing two different concentrations of bisphenol A, diethylstilbestrol, tributyltin, or E2. At the end, brains were processed for NPY and POMC immunohistochemistry and quantitatively analyzed. In the arcuate and dorsomedial nuclei, both NPY and POMC immunoreactivity showed a statistically significant decrease. In the paraventricular nucleus, only the NPY system was affected, while the POMC system was not affected. Finally, in the VMH the NPY system was affected whereas no POMC immunoreactive material was observed. These results indicate that adult exposure to different EDCs may alter the hypothalamic circuits that control food intake and energy metabolism.

Early Postnatal Genistein Administration Affects Mice Metabolism and Reproduction in a Sexually Dimorphic Way

“…In fact, PVN kiss fibers are part of a sexual network essential for the control of the HPG axis through the control of the GnRH system. The PVN is also rich in NPY and POMC fibers [ 82 ], as well as in orexin fibers (present study).…”

“…These neurons co-express different neuropeptides and a wide variety of receptors, including leptin receptors [ 80 ]. Moreover, the POMC system is sensitive to gonadal steroids [ 81 ], and we recently demonstrated that this system could be a good target for MDCs action by using a chronic exposure to tributyltin [ 57 ], as well as long-term exposure to BPA, DES, and TBT [ 82 ]. Here, we confirm that also early postnatal exposure to GEN induces long-term sex-specific organizational effects on the POMC system in the ARC and PVN.…”

“…Cell numbers in the ARC and their projections may respond differently to treatment with EDCs, which is particularly evident for the POMC system [ 57 , 82 ]. Present results show a reduction of POMC innervation of the PVN in females and an increase in males, while cell numbers in the ARC have an opposite trend.…”

“…POMC immunostaining was performed according to our previous studies [ 57 , 82 ], with an overnight incubation of floating sections at 4 °C with a rabbit polyclonal antibody against POMC (POMC precursor 27–52, H029-30, Phoenix Pharmaceuticals, Inc., Burlingame, CA, USA) diluted 1:5000 in PBS-Triton X-100 0.2%, pH 7.3–7.4. Sections were then incubated in biotinylated goat anti-rabbit IgG (Vector Laboratories, 1:250) for 60 min.…”

“…The antigen-antibody reaction was revealed as described for kisspeptin immunohistochemistry. The POMC antibody specificity for immunohistochemistry was tested by the factory and in previous studies [ 57 , 82 ].…”