Short-Term Hormone Release from Adult Female Rat Hypothalamic and Pituitary Explants is not Altered by 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Abstract

Abstract. 2, 3, 7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has adverse effects on reproduction, in part due to direct actions at the ovary. It is unclear whether effects are further mediated by glands that regulate ovarian function. We investigated whether effects of TCDD are mediated via the hypothalamic-pituitary axis. Hypothalamic and pituitary tissues were cultured in medium with and without TCDD. TCDD did not alter GnRH release from hypothalamic samples. It continued to be pulsatile with no differences in the average peak frequency, average peak amplitude, or baseline GnRH release. TCDD did not alter GnRH-induced release of gonadotropins from pituitary samples. There were no differences in average peak amplitude or baseline release. AhR, ARNT or ERα mRNA copy numbers in cultured pituitaries were not affected by TCDD. Our data suggest that TCDD effects on ovarian function are not mediated through the hypothalamic or pituitary release parameters tested in this study.

The Aryl Hydrocarbon Receptor and the Nervous System

“…Moreover, GnRH production and release is also inhibited by TCDD (5 µg/kg, GD15, gavage) in male rats, due to ultra-structural alterations of the GnRH-positive neurons [ 62 , 63 ]. However, this point is controversial in light of the results of Trewin et al, which do not show any alterations with short-term hormone release from adult female rat hypothalamic and pituitary explants, following exposure to 3.1 nM TCDD in the perfusion medium [ 64 ]. In terms of signaling, it has been hypothesized that GnRH can stimulate the activity of two protein kinases A and C (PKA and PKC), to increase gonadotropin expression, and that those two pathways are then be targeted by TCDD [ 65 ].…”

The Aryl Hydrocarbon ReceptorsansXenobiotics: Endogenous Function in Genetic Model Systems

“…Although the number and morphology of immature, preovulatory follicles is unchanged between wildtype and Ahr knockout females, several reports have noted a marked reduction in the number of mature follicles (Benedict et al, 2000(Benedict et al, , 2003Baba et al, 2005). Evidence indicates that these defects are not due to upstream changes in the endocrine regulation of ovulatory-stimulating hormones (Baba et al, 2005;Trewin et al, 2007). Rather, data suggest that maturation of Ahr-null follicles is disrupted as a result of insufficient synthesis of estrodiol within the follicle itself (Baba et al, 2005;Barnett et al, 2007).…”

Neuroendocrine disruption of pubertal timing and interactions between homeostasis of reproduction and energy balance

“…In such conditions, DDT resulted in effects similar to estradiol (Rasier et al, 2008). However, Trewin et al (2007) could not observe any change in pulsatile GnRH secretion caused by dioxin using hypothalamic explants from cycling adult female rats. The age difference could account for such discrepant observations since we did not observe at 25 and 50 days the stimulatory estradiol effects seen at 5 and 15 days (Matagne et al, 2004).…”

“…Direct disruption of the peripheral reproductive system involves predominantly effects mimicking estrogens in the female while counteracted androgen effects are involved peripherally in the male (Diamanti-Kandarakis et al, 2009). Since the reproductive system is regulated by feedback loops between gonads and peripheral tissues on the one hand and pituitary gland, hypothalamus and CNS on the other hand, direct peripheral effects of EDCs can secondar- (Rasier et al, 2007(Rasier et al, , 2008) Dioxin Adult rat F TCDD in vitro: no effect on pulsatile GnRH release (Trewin et al, 2007) MXC: methoxychlor; PCBs: polychlorinated biphenyls; ER: estrogen receptor; AhR: arylhydrocarbon receptor; DDT: dichlorodiphenyltrichloroethane; and TCDD: 2,3,7,8tetrachlorodibenzo-p-dioxin.…”