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Impact of add-back FSH on human and mouse prostate following gonadotropin ablation by GnRH antagonist treatment

Deiktakis, Eleftherios E. ; Ieronymaki, Eleftheria ; Zarén, Peter LU orcid ; Hagsund, Agnes ; Wirestrand, Elin ; Malm, Johan LU ; Tsatsanis, Christos LU ; Huhtaniemi, Ilpo T. LU ; Giwercman, Aleksander LU and Giwercman, Yvonne Lundberg LU (2022) In Endocrine Connections 11(6).
Abstract

Objective: During androgen ablation in prostate cancer by the standard gonadotropin-releasing hormone (GnRH) agonist treatment, only luteinizing hormone (LH) is permanently suppressed while circulating follicle-stimulating hormone (FSH) rebounds. We explored direct prostatic effects of add-back FSH, after androgen ablation with GnRH antagonist, permanently suppressing both gonadotropins. Methods: The effects of recombinant human (rFSH) were examined in mice treated with vehicle (controls), GnRH antagonist degarelix (dgx), dgx + rFSH, dgx + flutamide, or dgx + rFSH + flutamide for 4 weeks. Prostates and testes size and expression of prostate-specific and/or androgen-responsive genes were measured. Additionally, 33 young men underwent... (More)

Objective: During androgen ablation in prostate cancer by the standard gonadotropin-releasing hormone (GnRH) agonist treatment, only luteinizing hormone (LH) is permanently suppressed while circulating follicle-stimulating hormone (FSH) rebounds. We explored direct prostatic effects of add-back FSH, after androgen ablation with GnRH antagonist, permanently suppressing both gonadotropins. Methods: The effects of recombinant human (rFSH) were examined in mice treated with vehicle (controls), GnRH antagonist degarelix (dgx), dgx + rFSH, dgx + flutamide, or dgx + rFSH + flutamide for 4 weeks. Prostates and testes size and expression of prostate-specific and/or androgen-responsive genes were measured. Additionally, 33 young men underwent dgx-treatment. Seventeen were supplemented with rFSH (weeks 1–5), and all with testosterone (weeks 4–5). Testosterone, gondotropins, prostate-specific antigen (PSA), and inhibin B were measured. Results: In dgx and dgx + flutamide treated mice, prostate weight/body weight was 91% lower than in controls, but 41 and 11%, respectively, was regained by rFSH treatment (P = 0.02). The levels of seminal vesicle secretion 6, Pbsn, Nkx3.1, beta-microseminoprotein, and inhibin b were elevated in dgx + rFSH-treated animals compared with only dgx treated (all P < 0.05). In men, serum inhibin B rose after dgx treatment but was subsequently suppressed by testosterone. rFSH add-back had no effect on PSA levels. Conclusions: These data provide novel evidence for the direct effects of FSH on prostate sizand gene expression in chemically castrated mice. However, in chemically castrated men, FSH had no effect on PSA production. Whether FSH effects on the prostate in humans also require suppression of the residual adrenal-derived androgens and/or a longer period of rFSH stimulation, remains to be explored.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
castration, degarelix, follicle-stimulating hormone, prostate, PSA
in
Endocrine Connections
volume
11
issue
6
article number
e210639
publisher
BioScientifica
external identifiers
  • pmid:35575351
  • scopus:85133126702
ISSN
2049-3614
DOI
10.1530/EC-21-0639
language
English
LU publication?
yes
id
06f519b4-be72-425a-b9ea-282a3d63cee1
date added to LUP
2022-09-28 12:02:18
date last changed
2025-03-07 21:53:57
@article{06f519b4-be72-425a-b9ea-282a3d63cee1,
  abstract     = {{<p>Objective: During androgen ablation in prostate cancer by the standard gonadotropin-releasing hormone (GnRH) agonist treatment, only luteinizing hormone (LH) is permanently suppressed while circulating follicle-stimulating hormone (FSH) rebounds. We explored direct prostatic effects of add-back FSH, after androgen ablation with GnRH antagonist, permanently suppressing both gonadotropins. Methods: The effects of recombinant human (rFSH) were examined in mice treated with vehicle (controls), GnRH antagonist degarelix (dgx), dgx + rFSH, dgx + flutamide, or dgx + rFSH + flutamide for 4 weeks. Prostates and testes size and expression of prostate-specific and/or androgen-responsive genes were measured. Additionally, 33 young men underwent dgx-treatment. Seventeen were supplemented with rFSH (weeks 1–5), and all with testosterone (weeks 4–5). Testosterone, gondotropins, prostate-specific antigen (PSA), and inhibin B were measured. Results: In dgx and dgx + flutamide treated mice, prostate weight/body weight was 91% lower than in controls, but 41 and 11%, respectively, was regained by rFSH treatment (P = 0.02). The levels of seminal vesicle secretion 6, Pbsn, Nkx3.1, beta-microseminoprotein, and inhibin b were elevated in dgx + rFSH-treated animals compared with only dgx treated (all P &lt; 0.05). In men, serum inhibin B rose after dgx treatment but was subsequently suppressed by testosterone. rFSH add-back had no effect on PSA levels. Conclusions: These data provide novel evidence for the direct effects of FSH on prostate sizand gene expression in chemically castrated mice. However, in chemically castrated men, FSH had no effect on PSA production. Whether FSH effects on the prostate in humans also require suppression of the residual adrenal-derived androgens and/or a longer period of rFSH stimulation, remains to be explored.</p>}},
  author       = {{Deiktakis, Eleftherios E. and Ieronymaki, Eleftheria and Zarén, Peter and Hagsund, Agnes and Wirestrand, Elin and Malm, Johan and Tsatsanis, Christos and Huhtaniemi, Ilpo T. and Giwercman, Aleksander and Giwercman, Yvonne Lundberg}},
  issn         = {{2049-3614}},
  keywords     = {{castration; degarelix; follicle-stimulating hormone; prostate; PSA}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{BioScientifica}},
  series       = {{Endocrine Connections}},
  title        = {{Impact of add-back FSH on human and mouse prostate following gonadotropin ablation by GnRH antagonist treatment}},
  url          = {{http://dx.doi.org/10.1530/EC-21-0639}},
  doi          = {{10.1530/EC-21-0639}},
  volume       = {{11}},
  year         = {{2022}},
}