Xenoestrogens Ethinyl Estradiol and Zearalenone Cause Precocious Puberty in Female Rats via Central Kisspeptin Signaling

Kriszt, R. and Winkler, Zsuzsanna and Polyák, Ágnes and Kuti, D. and Molnar, C. and Hrabovszky, Erik and Kalló, Imre and Ferenczi, Szilamér and Kovács, Krisztina (2015) Xenoestrogens Ethinyl Estradiol and Zearalenone Cause Precocious Puberty in Female Rats via Central Kisspeptin Signaling. ENDOCRINOLOGY, 156 (11). pp. 3996-4007. ISSN 0013-7227


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Xenoestrogens from synthetic or natural origin represent an increasing risk of disrupted endocrine functions including the physiological activity of the hypothalamo-pituitary-gonad axis. Ethinyl estradiol (EE2) is a synthetic estrogen used in contraceptive pills, whereas zearalenone (ZEA) is a natural mycoestrogen found with increasing prevalence in various cereal crops. Both EE2 and ZEA are agonists of estrogen receptor alpha (ERalpha) and accelerate puberty. However, the neuroendocrine mechanisms that are responsible for this effect remain unknown. Immature female Wistar rats were treated with EE2 (10 mu g/kg), ZEA (10 mg/kg) or vehicle for 10 days starting from postnatal day 18. As a marker of puberty, vaginal opening was recorded and neuropeptide- and related transcription factor mRNA levels were measured by quantitative real time PCR and in situ hybridization histochemistry. Both ZEA and EE2 accelerated vaginal opening, increased uterine weight and the number of antral follicles in the ovary and resulted in increased central expression of gnrh. These changes occurred in parallel with an earlier increase of kiss1 mRNA in the anteroventral and rostral periventricular (AVPV/PeV) hypothalamus, and increased kisspeptin (KP) fiber density and KP-GnRH appositions in the preoptic area. These changes are compatible with a mechanism in which xenoestrogens overstimulate the developmentally unprepared reproductive system, which results in advanced vaginal opening and enlargement of the uterus at the periphery. Within the hypothalamus, ZEA and EE2 directly activate AVPV KP neurons to stimulate GnRH mRNA. However, GnRH and gonadotropin release and ovulation are disrupted due to xenoestrogen-mediated inhibitory KP signaling in the arcuate nucleus.

Item Type: Article
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkórtan, neurológia, pszichiátria
Depositing User: MTMT SWORD
Date Deposited: 21 Dec 2015 12:26
Last Modified: 21 Dec 2015 12:26

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