Oocyte-derived growth differentiation factor 9 suppresses the expression of CYP17A1 and androgen production in human theca cells.
Humans
Steroid 17-alpha-Hydroxylase
/ genetics
Theca Cells
/ metabolism
Female
Receptors, Transforming Growth Factor beta
/ metabolism
Growth Differentiation Factor 9
/ metabolism
Receptor, Transforming Growth Factor-beta Type I
/ metabolism
Smad2 Protein
/ metabolism
Smad3 Protein
/ metabolism
Androgens
/ metabolism
Receptors, LH
/ genetics
Protein Serine-Threonine Kinases
/ metabolism
Phosphoproteins
/ metabolism
Smad4 Protein
/ metabolism
Phosphorylation
/ drug effects
Cells, Cultured
Oocytes
/ metabolism
Androstenedione
/ metabolism
Testosterone
/ metabolism
Receptor, Transforming Growth Factor-beta Type II
/ genetics
Signal Transduction
/ drug effects
Growth differentiation factor 9
androgen
polycystic ovary syndrome
theca cell
Journal
F&S science
ISSN: 2666-335X
Titre abrégé: F S Sci
Pays: United States
ID NLM: 101765857
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
received:
05
06
2023
revised:
19
10
2023
accepted:
23
10
2023
medline:
9
10
2024
pubmed:
9
10
2024
entrez:
9
10
2024
Statut:
ppublish
Résumé
To investigate the direct effect of growth differentiation factor 9 (GDF9) on androgen production in human theca cells. Experimental study. Tertiary hospital-based research laboratory. Women who underwent in vitro fertilization and intracytoplasmic sperm injections at our clinic were included in this study. Primary cultured human theca cells from women undergoing in vitro fertilization and intracytoplasmic sperm injection treatment were treated with GDF9, an activin receptor-like kinase 5 (ALK5) inhibitor, and a SMAD4 agonist. The expression of androgen synthesis-related genes StAR, CYP17A1, and LHCGR, levels of androstenedione and testosterone, phosphorylation of SMAD2/3, and the interaction between bone morphogenic protein-activated type II receptor and ALK5 were evaluated using reverse transcription-quantitative polymerase chain reaction, Western blot, enzyme-linked immunosorbent assays, and coimmunoprecipitation assays, respectively. Growth differentiation factor 9 decreased StAR, CYP17A1, and LHCGR expression levels in human theca cells, which was prevented by treatment with the ALK5 inhibitor, and suppressed production of androgen in human theca cells. Growth differentiation factor 9 increased SMAD2/3 phosphorylation, and the ALK5 inhibitor also suppressed this effect. Bone morphogenic protein-activated type II receptor and ALK5 bound to each other after GDF9 stimulation. The SMAD4 agonist kartogenin also decreased messenger RNA levels of StAR and CYP17A1 and protein levels of StAR in human theca cells. Growth differentiation factor 9 can activate the bone morphogenic protein-activated type II receptor-ALK5-SMAD2/3 signaling pathway, suppress CYP17A1 expression, and decrease androgen production in human theca cells.
Identifiants
pubmed: 39382269
pii: S2666-335X(23)00060-5
doi: 10.1016/j.xfss.2023.10.005
pii:
doi:
Substances chimiques
Steroid 17-alpha-Hydroxylase
EC 1.14.14.19
CYP17A1 protein, human
EC 1.14.14.19
TGFBR1 protein, human
EC 2.7.11.30
Receptors, Transforming Growth Factor beta
0
Growth Differentiation Factor 9
0
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
Smad2 Protein
0
Smad3 Protein
0
Androgens
0
Receptors, LH
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
LHCGR protein, human
0
Phosphoproteins
0
Smad4 Protein
0
GDF9 protein, human
0
steroidogenic acute regulatory protein
0
SMAD3 protein, human
0
SMAD2 protein, human
0
Androstenedione
409J2J96VR
Testosterone
3XMK78S47O
Receptor, Transforming Growth Factor-beta Type II
EC 2.7.11.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16-23Informations de copyright
Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declarations of competing interest X.G. has nothing to disclose. Y.Z. has nothing to disclose. Y.L. has nothing to disclose. R.W. has nothing to disclose. L.H. has nothing to disclose. C.H. has nothing to disclose. M.C. has nothing to disclose.