Adrenal androgens rescue prostatic dihydrotestosterone production and growth of prostate cancer cells after castration.

[pjoshea13]

New study below [1] which sheds light on the role of adrenal hormones in PCa progression while on ADT.

In the context of Zytiga, one often hears that the drug inhibits adrenal androgen production and that the adrenals produce a small but significant percentage of total testosterone [T]. But I associate the adrenals with DHEA, rather than T.

The following quotes are from Wikipedia [2] "Adrenal gland".

"Each gland has an outer cortex which produces steroid hormones and an inner medulla."

"The adrenal cortex itself is divided into three zones: the zona glomerulosa, the zona fasciculata and the zona reticularis."

"The zona reticularis ... produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and androstenedione". "In general, these hormones do not have an overall effect in the male body, and are converted to more potent androgens such as testosterone and DHT ... in the gonads, acting in this way as a metabolic intermediate."

So T derived from adrenal sources actually comes from the gonads. No gonads = no adrenal T?

But adrenal DHEA, DHEA-S and androstenedione are also available directly to PCa cells. The new study looked at the effect of DHEA & DHEA-S on fresh human prostate tissue and PCa cell lines.

DHEA & DHEA-S "are potential substrates for intracrine production of testosterone (T) and dihydrotestosterone (DHT), or directly to DHT, by prostate cancer (PCa) cells."

"DHEA-S at a physiological concentration was converted to DHT in prostate tissue and PCa cell lines"

"DHEA at a physiological concentration was not converted to DHT .., but stimulated in vivo tumor growth of the human PCa cell line, VCaP, in castrated mice."

"The findings suggest that targeting metabolism of DHEAS and DHEA may enhance androgen deprivation therapy." Oh no, not another ADT add-on drug! LOL.

Zytiga inhibits adrenal conversion of pregnenolone to DHEA, & thus to its sulfated form, DHEA-S. (It also inhibits conversion of progesterone to androstenedione.)

- Patrick

[1] ncbi.nlm.nih.gov/pubmed/308...

Mol Cell Endocrinol. 2019 Feb 23. pii: S0303-7207(19)30064-4. doi: 10.1016/j.mce.2019.02.018. [Epub ahead of print]

Adrenal androgens rescue prostatic dihydrotestosterone production and growth of prostate cancer cells after castration.

Wu Y1, Tang L2, Azabdaftari G3, Pop E4, Smith GJ4.

Author information

1

Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. Electronic address: [e-mail].

2

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

3

Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

4

Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Abstract

Adrenal androgens dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) are potential substrates for intracrine production of testosterone (T) and dihydrotestosterone (DHT), or directly to DHT, by prostate cancer (PCa) cells. Production of DHT from DHEAS and DHEA, and the role of steroid sulfatase (STS), were evaluated ex vivo using fresh human prostate tissue and in vitro using human PCa cell lines. STS was expressed in benign prostate tissue and PCa tissue. DHEAS at a physiological concentration was converted to DHT in prostate tissue and PCa cell lines, which was STS-dependent. DHEAS activation of androgen receptor (AR) and stimulation of PCa cell growth were STS-dependent. DHEA at a physiological concentration was not converted to DHT ex vivo and in vitro, but stimulated in vivo tumor growth of the human PCa cell line, VCaP, in castrated mice. The findings suggest that targeting metabolism of DHEAS and DHEA may enhance androgen deprivation therapy.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS:

Adrenal androgen; Androgen; Intracrine androgen metabolism; Metabolism; Prostate cancer; Steroid sulfatase

PMID: 30807787 DOI: 10.1016/j.mce.2019.02.018

[2] en.wikipedia.org/wiki/Adren...

[j-o-h-n]

"Adrenal androgens rescue prostatic dihydrotestosterone production and growth of prostate cancer cells after castration".

You know I speak Greek, but that's Greek to me.

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 02/28/2019 7:18 PM EST

[GoBucks in reply to j-o-h-n]

My Greek buddies call me Malaka. Is that a Greek pastry?

[j-o-h-n in reply to GoBucks]

Yes, it's made with 5 fingers and a lot of effort....watching a good Porno helps too

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 02/28/2019 8:41 PM EST

[Bluebird11]

I've read through as much DHEA info as possible and I'm still confused.

Can someone give a rule of thumb why it would be recommended for PCa?

Why some men are saying it's difficult to take?

There seems to be a time limit as far as taking it, meaning, for something specific.

One of our docs recommended it. When something is recommended unless I go over the supplements my husband tends to continue taking the supplement sometimes after the specific reason initially...

7-Keto DHEA 50mg

Thanks very much. I try to help others just beginning this journey to give back. These supplements and information at this point is becoming more of a challenge to understand.

I have to get back on the horse and ride again. thank you all very much...

[pjoshea13 in reply to Bluebird11]

While on ADT, a man should not take DHEA. The cancer cells might use DHEA to make DHT.

-Patrick

[jimbob99999 in reply to pjoshea13]

Thanks for the clear response. Several documents in NIH are contradictory on DHEA.

[Bluebird11]

Thank's Patrick... very clear... and I'm not sure why one of our docs recommended this...

It's so difficult to wade through all aspects of this whether supplements or prescription drugs...

I appreciate your quick response....

[jimbob99999]

Hi Nalakrats, do Avodart and/or Proscar create the ADT side-effects like sweating, bone loss, muscle loss?

Thanks in advance.

Jim

[pjoshea13 in reply to jimbob99999]

JimBob,

IMO - no such luck.

The 5alpha reductase inhibitors are a safety play (a nod to Nalakrats who is a serious bridge player). ADT is supposed to starve PCa of dihydrotestosterone [DHT], but PCa can find alternative pathways to create DHT.

-Patrick