Oral Presentation The International Congress of Neuroendocrinology 2014

Estrogen modulation of lactotroph proliferation (#17)

Jun Arita 1 , Maho Ishida 1 , Tetsuo Mitsui 1
  1. University of Yamanashi, Chuo-shi, Yamanashi, Japan

In typical estrogen-responsive tissues such as the uterus, mammary gland, and anterior pituitary gland, estrogens have profound proliferative actions, which are not only essential for normal development and reproductive functions in females but also involved in the pathogenesis of tumors originating in these tissues. Estradiol is the most important regulator of pituitary lactotrophs which synthesize and secrete prolactin. Estradiol secreted between diestrus II and proestrus induces the surge of prolactin secretion at proestrus and the proliferation of lactotrophs at estrus during the 4-day estrous cycle of the rat. This every 4-days proliferation produces a marked sex difference after puberty in the number of lactotrophs, thereby filling a need for high prolactin secretion during the following pregnancy and lactation. The finding that pentobarbital anesthesia during the proestrous afternoon blocks the surge of prolactin secretion and the proliferation of lactotrophs suggests that a neural event activated by estradiol is involved in the regulation of lactotroph proliferation. The direct action of estradiol on lactotrophs is also implicated by the finding that treatment with an antiestrogen that cannot cross the blood-brain barrier blocks lactotroph proliferation at estrus. Our aim is to elucidate how estradiol modulates proliferation of lactotrophs in primary culture. We found that stimulation of lactotroph proliferation needed treatment with estradiol alone for no less than 96 h but was induced immediately by treatment with estradiol in combination with serum or forskolin, an intracellular cyclic AMP concentration-increasing agent. Importantly, lactotroph proliferation was inhibited after treatment with estradiol in combination with growth factors such as insulin and insulin-like growth factor-1 suggesting that estradiol has not only proliferative but also opposing anti-proliferative actions on lactotrophs depending upon the cell context in primary culture. Understanding the mechanism of the actions of estradiol on proliferation, particularly the anti-proliferative action, may provide novel therapeutic approaches to estrogen-responsive tumors.