Oestrogenic action of neonatal tamoxifen on the hypothalamus and reproductive system in female mice
Rahmatollah Parandin A , Morteza Behnam-Rassouli A B and Nasser Mahdavi-Shahri A
+ Author Affiliations
- Author Affiliations
A Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, PO Box 91775-1436, Mashhad 9177948974, Iran.
B Corresponding author. Email: behnam@um.ac.ir
Reproduction, Fertility and Development 29(5) 1012-1020 https://doi.org/10.1071/RD15361
Submitted: 5 September 2015 Accepted: 29 January 2016 Published: 11 April 2016
Abstract
Tamoxifen, a selective oestrogen receptor modulator, is widely used for both the treatment and prevention of breast cancer in women; however, it is known to have adverse effects in the female reproductive system. Growing evidence suggests that oestrogen-sensitive neuron populations of the anteroventral periventricular (AVPV) nucleus and arcuate (ARC) nucleus, especially kisspeptin neurons, play a pivotal role in the timing of puberty onset and reproductive function. The aim of the present study was to evaluate whether neonatal exposure to tamoxifen affects oestrogenic actions in the brain and reproductive function in mice. On 1 to 5 postnatal days, female pups were injected subcutaneously with sesame oil (sham), oestradiol benzoate (EB; 20 µg kg–1), tamoxifen (0.4 mg kg–1) or EB+tamoxifen. Control mice received no treatment. Mice in the EB, tamoxifen and tamoxifen+EB groups exhibited advanced vaginal opening, disrupted oestrous cycles and a decreased follicular pool. Conversely, in these groups, there was a reduction in kisspeptin (Kiss1) mRNA expression, the neuronal density of AVPV and ARC nuclei and LH and oestradiol concentrations in the serum. The results of the present study confirm oestrogenic actions of tamoxifen in the brain and reproductive system. In addition, we show, for the first time, that tamoxifen has oestrogenic effects on the oestrogen-sensitive hypothalamic AVPV and ARC nuclei controlling the reproductive axis in female mice.
Additional keywords: neuroendocrinology, oestrogen, oestrous, ovary.
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