Nerve growth factor, D2 receptor isoforms, and pituitary tumors

Excerpt

Dopamine (DA), by interacting with D2 receptors (D2R), exerts two major effects in the anterior pituitary: It inhibits prolactin (PRL) secretion and controls lactotrope cell proliferation, playing a role during pituitary development and tumorigenesis. In 1982, it was first reported that the spontaneous development of prolactinomas in old female rats was associated with the loss of hypothalamic DA neurons and that young female rats with estrogen-induced prolactinomas had damaged tuberoinfundibular DA neurons [1]. More recently, the development of transgenic mice lacking either the DA transporter (DAT) or the D2R pointed to the crucial role of DA in the control of lactotrope cell proliferation and in the pathogenesis of prolactinomas. Ablation of DAT, which physiologically controls DA function by mediating its re-uptake into nerve terminals, leads to a generalized dopaminergic hypertone, including increased DA overflow to the anterior pituitary. As a result, these mice developed hypopituitarism due to a defect in the proliferation and migration of lactotrope and somatotrope cells [2]. In D2R knockout mice, on the other hand, the control of hypothalamic DA over pituitary function was lost due to the lack of D2R expression, resulting in proliferation of lactotrope cells and in the development of prolactinomas in the older animals [3]. …