I have been meaning to tackle prolactin (PRL) for at least a dozen years, but there are hundreds of PCa papers and who has the time? It's an important topic that is rarely mentioned.
A recent paper (Jan 13, 2003 - my 75th birthday, so how could I ignore it?) has this in the intro (note - PRLR is the PRL receptor):
"In canonical signaling, PRL binding to PRLR induces downstream signaling including JAK-STAT, AKT and MAPK pathways. This leads to increased cell proliferation, stemness, migration, apoptosis inhibition, and resistance to chemotherapy. "
My last post on the topic was 4 years ago (elsewhere). It was prompted by a paper by Costello & Franklin [2]. A man with CRPC:
"was treated with cabergoline (dopamine agonist) treatment, which decreased the plasma prolactin 88%; by inhibiting the pituitary production of prolactin. The subsequent PET scan (positron emission tomography) revealed the absence of malignancy; and the CTC (circulating tumor cells) decreased from count=5.4 to count=0."
Back in the day, men would travel from afar to see Dr. Strum.
"Medical Oncologist Stephen Strum ... : “If the fasting prolactin is 5.0 or higher, start Dostinex (cabergoline) at 0.25 mg every Monday, Wednesday, and Friday. A month later recheck the prolactin level.”" [3]
I mentioned in the post that my prolactin was much higher than 5 & I was using NOW Foods DOPA Mucuna (Mucuna pruriens seed - minimum 15% DOPA) in an attempt to bring it down [4]. I still use it but haven't tested prolactin since covid hit.
"pituitary PRL synthesis and release is sensitive to regulation by dopamine" [DOPA] [1]
"Prolactin (PRL) and its cognate receptor, prolactin receptor (PRLR), have been characterized in hundreds of biological functions, especially mammary gland development and lactation. PRL is a peptide hormone that resembles the growth hormone ...
"It is largely produced by the lactotrope cells of the anterior pituitary gland as a pro-hormone ...
"However, aberrant PRL levels are also observed in disease states, which may also be related to its synthesis from the affected tissues including the prostate ... {DOPA will probably not be useful, to that extent.}
"It can therefore participate in paracrine and autocrine signaling functions related to cell homeostasis and growth ..."
The paper goes on to review the history of experimental drugs. No need to spend time on this lengthy catalog of failures (imo).
From the summary/conclusion:
"It is becoming clear that PRLR mediated signaling plays a critical role in multiple human diseases and malignancies, and therefore is an attractive target for developing therapies. Since the early 1990s, researchers have attempted to generate PRLR antagonists and inhibitors with mixed success in pre-clinical and clinical applications. While none of these studies have resulted in FDA approval to date, they have provided a foundation for future discoveries that may yet be exploited. At the very least, our understanding of PRLR biology has expanded, and the studies to date have provided tools to interrogate this to greater depths.
First generation human PRL analogs exhibited weak agonistic activity towards PRLR despite numerous studies demonstrating antagonism, leading to reluctance for use in clinic. This contributed to the development of second generation analogs, such as Δ1–9-G129R-hPRL, which exhibits pure antagonism across multiple bioassays. Unfortunately, there remain challenges for clinical applications. Since these antagonists are small peptides (~23 kDa), these are quickly filtered by the kidneys, leading to suboptimal half-lives to maintain a potent and durable response. Nevertheless, the high selectivity of these analogs remains attractive with clinical prospects."
Bottom line:
i) Prolactin is important - particularly hyperprolactinemia. Do you know your prolactin level?
ii) Cabergoline may be helpful in bringing prolactin levels down.
iii) DOPA Mucuna is an over-the-counter alternative
-Patrick
[1] ncbi.nlm.nih.gov/pmc/articl...
[2] pubmed.ncbi.nlm.nih.gov/312...
