Hypothalamic Effects of Tamoxifen on Oestrogen Regulation of Luteinising Hormone and Prolactin Secretion in Female Rats

Oestradiol (E₂) acts in the hypothalamus to regulate luteinising hormone (LH) and prolactin (PRL) secretion. Tamoxifen (TX) has been extensively used as a selective oestrogen receptor modulator, although its neuroendocrine effects remain poorly understood. In the present study, we investigated the hypothalamic effects of TX in rats under low or high circulating E₂ levels. Ovariectomised (OVX) rats treated with oil, E₂ or TX, or E₂ plus TX, were evaluated for hormonal secretion and immunohistochemical analyses in hypothalamic areas. Both E₂ and TX reduced LH levels, whereas TX blocked the E₂‐induced surges of LH and PRL. TX prevented the E₂‐induced expression of progesterone receptor (PR) in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC), although it did not alter PR expression in OVX rats. TX blocked the E₂ induction of c‐Fos in AVPV neurones, consistent with the suppression of LH surge. However, TX failed to prevent E₂ inhibition of kisspeptin expression in the ARC. In association with the blockade of PRL surge, TX increased the phosphorylation of tyrosine hydroxylase (TH) in the median eminence of OVX, E₂‐treated rats. TX also precluded the E₂‐induced increase in TH expression in the ARC. In all immunohistochemical analyses, TX treatment in OVX rats caused no measurable effect on the hypothalamus. Thus, TX is able to prevent the positive‐ but not negative‐feedback effect of E₂ on the hypothalamus. TX also blocks the effects of E₂ on tuberoinfundibular dopaminergic neurones and PRL secretion. These findings further characterise the anti‐oestrogenic actions of TX in the hypothalamus and provide new information on the oestrogenic regulation of LH and PRL.