Drug Insight: prolactin-receptor antagonists, a novel approach to treatment of unresolved systemic and local hyperprolactinemia?

摘要

Prolactin is a polypeptide hormone whose major biological actions are related to normal lactation and reproduction. Abnormally high prolactin levels, referred to as hyperprolactinemia, can result in various reproductive disorders. Currently, therapeutic management of hyperprolactinemia relies on dopamine agonists, since dopamine is the primary physiological suppressor of pituitary prolactin production. Epidemiologic studies have shown that prolactin levels in the high-normal range, as well as medications that interfere with dopamine action (e.g. certain antipsychotic drugs), might correlate with increased breast cancer risk. In addition to circulating prolactin, it is now well established that prolactin is also produced locally within various tissues, including breast and prostate. Increasing evidence, mainly from animal studies at present, suggests that excess locally produced prolactin may promote the growth of breast and prostate tumors via an autocrine or paracrine mechanism. These findings have renewed the interest in finding alternative strategies to suppress prolactin actions when dopamine agonists are ineffective. Our studies of the relationship between prolactin structure and function have resulted in the development of pure prolactin-receptor antagonists. These molecules prevent endogenous prolactin from exerting its actions via a competitive mechanism for receptor binding. In this review, we discuss the possible future therapeutic utility of this novel class of compounds.