The Role of Uron and Chlorobenzene Derivatives, as Potential Endocrine Disrupting Compounds, in the Secretion of ACTH and PRL

Abstract

Uron herbicides polluting the environment represent a serious concern for environmental health and may be regarded as endocrine-disrupting compounds (EDCs), which influence the regulation of human homeostasis. We aimed to investigate the effect of EDC urons (phenuron: PU, monuron: MU, and diuron: DU) and chlorobenzenes on the basal release of the adrenocorticotropic hormone (ACTH), which is a part of the adenohypophysis-adrenocortical axis. Hormone secretion in the presence of EDC was studied in two cell types: normal adenohypophysis cells (AdH) and cells of prolactinomas (PRLOMA). PRLOMA was induced in female Wistar rats by subcutaneously injecting them with estrone acetate for 6 months. AdH and PRLOMA were separated from treated and untreated experimental animals, dissociated enzymatically and mechanically in order to create monolayer cell cultures, which served as an experimental in vitro model. We investigated the effects of ED agents separately and in combination on ACTH and prolactin (PRL) release through the hypophyseal-adrenal axis. Hormone determination was carried out by the luminescent immunoassay and the radioimmunoassay methods. Our results showed that (1) uron agents separately did not change ACTH and PRL release in AdH culture; (2) ACTH secretion in arginine vasopressin- (AVP-) activated AdH cells was significantly increased by EDC treatment; (3) ED agents increased the basal hormone release (ACTH, PRL) in PRLOMA cells; and (4) EDC exposure increased ACTH release in AVP-activated PRLOMA cells. We conclude that the herbicides PU, MU, and DU carry EDC effects and show human toxicity potential.

Study of the Potential Endocrine-Disrupting Effects of Phenylurea Compounds on Neurohypophysis Cells In Vitro

“…The effects of PU, MU, and DU added to the NH for 60 minutes at concentration of 10 −6 M were examined one by one [36]: PU CAS registry number: 101-42-8, DU CAS registry number: 330-54-1, and MU CAS registry number: 150-68-5 (Sigma, Germany). In our earlier studies, dose-dependent kinetics of phenylurea agents were determined, and the experimental doses were selected, because the saturation of receptor-binding sites depends on the affinity and number of receptor-binding molecules.…”

Examination of endocrine disruptor effects in neuroendocrine systems, in vivo and in vitro

“…In the outlined in vitro model, a primary ED effect has been demonstrated for the functioning of healthy and benign adenohypophysis cells in an essential function of ACTH release. As regards non-essential prolactin production, different secreted hormone levels were detected in the baseline interpretation of AdH versus PRLOMA cells (Table 4) (45).…”

“…was induced with AVP, which significantly increases ACTH release in healthy endocrine regulation (+ AVPAdH: 10220.88 ± 20.36), and is inhibited by corticosterone (B) (+ BAdH:1502.17 ± 3.25)(45). Studying the same control cycle with PRLOMA (+ AVPPRLOMA: 12674.50 ± 7.23; + BPRLOMA: 2155.50 ± 7.04), we found that the regulatory pattern persists but with slightly different ratios.…”

Környezeti hatótényezők endokrin diszruptor (ED) hatásainak experimentális vizsgálata és kapcsolata a kardiovaszkuláris klinikai gyakorlattal

“…α-MSH, β-MSH és γ-MSH, melyek eltérő affinitással kötődnek receptoraikhoz. MC-R-t a központi idegrendszeren kívül a perifériás szervekben (mellékvesekéreg, bőr, gasztrointestínum, pankreasz, vese, szív, tesztisz, ováriumok) A ClB-ok ösztrogénszerű hatásai is igazoltak [193,194], amelyen keresztül feltételezhetően az adenohipofízisben prolaktinomák kialakulásához [195], de a periférián vazokonstrikcióhoz is [196] vezethetnek. A ClB-ok jelentős ROS képzők [197].…”

“…A kísérleti (kontrollok és halogénezett és/vagy aromás -6 M) aktivált hormonvolumenek detektálása után, az adott kísérleti protokoll szerint önállóan (mClB, PU, MU, DU) és monoamin kombinációban (NA+mClB; NA+PU; NA+MU, NA+DU; 5-HT+mClB, 5-HT+PU, 5-HT+MU, 5-HT+DU) történt a kezelés (n=10/csoport). A protokollok szerinti kísérleti időpontokban történt a felülúszó médiumokból a mintavétel (500 µl) speciális műanyag csövekbe és a mérésig -70ºC-on tároltuk a mintákat[195]. (Immulite 2000, Siemens Healthcare Diagnostic, Deerfield, IL, USA, és DPC kit (L2KAC- 2; Euro/DPC Ltd, Glyn Rhonwy, UK) [39,195,225]).…”