Effects of Exposure to Estradiol Benzoate or Flutamide at the Weaning Age on Expression of Connexins in the Caudal Epididymis of Adult Rat

Abstract

The present research was chiefly designed to determine the effect of the treatment of estrogenic agonist, estradiol benzoate (EB), or antiandrogenic compound, flutamide (Flu), at the weaning age on the expression of connexin (Cx) isoforms in the caudal epididymis of adult male rat. Animals were subcutaneously administrated with a single shot of either EB at a low-dose (0.015 µg of EB/kg body weight (BW)) or a high-dose (1.5 µg of EB/kg BW) or Flu at a low-dose (500 µg of EB/kg BW) or a high-dose (5 mg of EB/kg BW). Expressional changes of Cx isoforms in the adult caudal epididymis were examined by quantitative real-time PCR analysis. The treatment of a low-dose EB caused significant increases of Cx30.3, Cx31, Cx32, and Cx43 transcript levels but reduction of Cx31.1, Cx37, and Cx45 expression. Exposure to a high-dose EB resulted in very close responses observed in a low-dose EB treatment, except no significant expressional change of Cx37 and a significant induction of Cx40. Expression of all Cx isoforms, except Cx45, was significantly increased by a low-dose Flu treatment. Expressional increases of all Cx isoforms were detected by a high-dose Flu treatment. The current study demonstrates that a single exposure to estrogenic or antiandrogenic compound during the early postnatal developmental period is sufficient to disrupt normal expression of Cx isoforms in the adult caudal epididymis.

Aberrant Expression of Cx Isoforms in the Adult Caput Epididymis exposed to Estradiol Benzoate or Flutamide at the Weaning

“…Aberrant expression of Cx isoforms in the adult corpus and caudal epididymis after Flu or EB treatment at the weaning has been reported from our previous researches ( Lee & Lee, 2015 ; Lee 2016b ). Each Cx isoform has shown different responses to Flu or EB treatment at the weaning age according to the epididymal region and/or dose of treatment.…”

“…For example, expression of Cx 26 in the adult corpus epididymis is significantly increased by a high-dose EB treatment but significantly decreased by a high-dose Flu treatment ( Lee & Lee, 2015 ). With the same treatment, in the adult caudal epididymis, expression of Cx 26 is not changed by EB treatment but significantly increased by Flu treatment at two doses ( Lee, 2016b ). Different expressional response of Cx 43 has been observed in corpus and caudal epididymis after the same Flu or EB treatment.…”

“…In addition, our previous researches have demonstrated the effects of flutamide and estradiol benzoate (EB), an estrogenic compound, treatments at the early neonatal age on expression of Cx isoforms within different epididymal segments ( Lee, 2015 , 2016a , 2017 ). Moreover, the exposure of these substances at different postnatal age results in differential expression of Cx isoforms within corpus or caudal epididymal region ( Lee, 2015 , 2016a , 2016b ; Lee & Lee, 2015 ). Recently, after the exposure to Flu or EB at the early neonatal age, expressional changes of Cx isoforms in the adult caput epididymis have been evaluated ( Lee, 2017 ).…”

The effects of flutamide on the neonatal rat hypothalamic–pituitary–adrenal and gonadal axes in response to hypoxia

“…Furthermore, flutamide may act as an agonist in the rat brain and mimic the neuroprotective effects of testosterone (Fanaei, Sadeghipour, Karimian, & Hassanzade, 2013). The agonistic actions of flutamide can occur via mechanisms that depend on the AR in both neuronal and non-neuronal cells (Lee, 2016a(Lee, , 2016bMacLusky et al, 2004;Nguyen et al, 2007) as well as other off-target effects (Foster et al, 2011). Therefore, the suppression of ACTH observed in our study could be the result of AR agonism in the neonatal rat brain.…”

“…Unexpectedly, standard dose flutamide suppressed the ACTH response to hypoxia in male and female PD7 pups. Flutamide demonstrated some agonistic activity which has previously been demonstrated (Lee, 2016b;MacLusky, Hajszan, & Leranth, 2004;Nguyen et al, 2007). This agonist effect may be due to dose-dependent receptor activation and conformational changes (Wong, Kelce, Sar, & Wilson, 1995).…”