Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No.
1 • January-February 2012
Beyond PSA Elevated Prolactin Levels:
Another Major Risk Factor for Prostate Cancer
Prolactin, although better known as the hormone that induces human lactation, also acts as a local growth factor in the prostate gland. Recent research now identifies increased local overexpression of prolactin (that which is produced locally in the prostate, though prolactin is also produced and released into the circulation from the anterior pituitary gland of the brain) as an amplifier of the pool of basal/stem cells which have been identified as originators of prostate cancer. Moreover, the locally produced prolactin may mediate the progression of castrate-resistant (androgen independent) cancer.
Although elevated circulating levels of prolactin “are not clearly linked to increased prostate risk,” there is now growing evidence of such a link to excess local (within the prostate gland) production of prolactin. The circulating prolactin and locally produced prolactin share the same sequence and are believed to exhibit the same efficacy towards the prolactin receptor; however, “it is possible that local prolactin secreted directly into the extracellular space achieves elevated concentrations and saturates the PRLRs [prolactin receptors].”
The researchers report that “analysis of human prostate cancer specimens showed prolactin immunostaining in 54% of a series of 80 prostate cancer specimens, and was positively correlated with high Gleason scores and activation of Stat5a/b, its major signaling protein. Furthermore, prolactin was also expressed in 50% of recurrent prostate cancer samples in a series of 183 specimens, including hormone-refractory cancer (54% of positive cases), and those from patients with lymph node metastases (67%).”
The usual treatment of excess prolactin derived from the pituitary is with dopamine agonists such as bromocriptine (Parlodel) that trigger the D2 dopamine receptor (D2R) on lactotroph cells. “However the efficacy of this class of drugs in regulating the prolactin gene in the human prostate (as in other extrapituitary sources) has yet to be demonstrated, and based on the fact that D2R expression has only been occasionally reported in human prostate samples,” according to papers cited by the authors, “they are anticipated to be ineffective for targeting extrapituitary prolactin expression.” We will not know for sure until further research is done.
According to the authors, “[p]rolactin has recently entered the limited panel of nonandrogenic signaling pathways that are emerging as potential candidates for targeted therapy in a subset of prostate cancer patients. Indeed, evidence has accumulated within the past few years to suggest that activation of Stat5, the downstream effector of the canonical PRLR [prolactin receptor] signaling pathway, has a key role in prostate cancer progression.”
In the meantime, we would consider it prudent for those with elevated circulating prolactin levels (levels above the normal range) to reduce those levels to low to mid normal range with a therapy such as bromocriptine.
- Goffin et al. Prolactin regulation of the prostate gland: a female player in a male game. Nat Rev Urol 8:597-607 (2011).