Abstract
Over the last years, increasing evidence has focused on crucial pathogenetic role of PRL on malignant, premalignant and benign uterine diseases. Studies in animals and humans have documented that PRL receptors (PRL-Rs) are widely expressed on uterine cells and that PRL is directly synthesized by the endometrium under the stimulatory action of progesterone. Uterine PRL secretion is finely modulated by autocrine/paracrine mechanisms which do not depend on the same control factors implied in the regulation of PRL secretion from pituitary. On the other hand, PRL is synthesized also in the myometrium and directly promotes uterine smooth muscle cell growth and proliferation. Therefore, PRL and PRL-Rs appear to play an important role for the activation of signaling pathways involved in uterine cancers and preneoplastic lesions. Circulating PRL levels are reportedly increased in patients with cervical or endometrial cancers, as well as uterine premalignant lesions, and might be used as discriminative biomarker in patients with uterine cancers. Similarly, increased PRL levels have been implicated in the endometriosis-induced infertility, albeit a clear a causative role for PRL in the pathogenesis of endometriosis is yet to be demonstrated. This evidence has suggested the potential application of dopamine agonists in the therapeutic algorithm of women with malignant, premalignant and benign uterine lesions. This review focuses on the role of PRL as tumorigenic factor for uterus and the outcome of medical treatment with dopamine agonists in patients with malignant and benign uterine disease.
Highlights
Besides lactotroph cells of anterior pituitary gland [1], prolactin (PRL) is synthesized in multiple non-pituitary sites including endometrium and myometrium [2]
Serum PRL levels are reportedly increased in patients with cervical and endometrial cancers, so that to be proposed as biomarker for malignant uterine diseases
Hyperprolactinemia is commonly found in endometrosis and is known to negatively influence fertility and pregnancy rate in women with this disease
Summary
Besides lactotroph cells of anterior pituitary gland [1], prolactin (PRL) is synthesized in multiple non-pituitary sites including endometrium and myometrium [2]. Resistance to dopamine agonists was diagnosed on the basis of lack of PRL normalization after medical treatment, and reversal of hyperprolactinemia was induced only by hysterectomy, suggesting that in selected cases extra-pituitary sources of PRL excess should be considered in women with proven resistance to dopamine agonists [43,44,45] These studies have highlighted that PRL finely regulate the pathogenesis of malignant, premalignant and benign uterine diseases, by directly influencing tumorigenesis in cervical and endometrial cancers, as well as cell growth and proliferation in uterine myomatosis likely with an autocrine or paracrine mechanism. PRL might be suggested as potential biomarker for malignant and benign uterine disease, and the use of dopamine agonists bromocriptine and cabergoline might be proposed as adjunctive treatment in such patients to help in restraining tumor growth or to alleviate symptoms in those who can preserve uterus [42]
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