The effect of androgens on ovarian follicle maturation

Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARÎ 3-dependent PTEN expression.

Mei Jou Chen, Chia Hung Chou, Shee Uan Chen, Wei Shiung Yang, Yu Shih Yang, Hong Nerng Ho

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPARÎ 3) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPARÎ 3 and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPARÎ 3 dependent PTEN/p-Akt expression in the granulosa cells.

Original languageEnglish
Article number18319
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - Dec 17 2015

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Peroxisome Proliferator-Activated Receptors
Ovarian Follicle
Dihydrotestosterone
Granulosa Cells
Follicle Stimulating Hormone
Androgens
Cell Proliferation
Polycystic Ovary Syndrome
Estrus
Hyperandrogenism
G2 Phase
PPAR gamma
Cyclin D1
Proliferating Cell Nuclear Antigen
Cell Division
Weight Gain
Placebos
Body Weight

ASJC Scopus subject areas

  • General

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The effect of androgens on ovarian follicle maturation : Dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARÎ 3-dependent PTEN expression. / Chen, Mei Jou; Chou, Chia Hung; Chen, Shee Uan; Yang, Wei Shiung; Yang, Yu Shih; Ho, Hong Nerng.

In: Scientific Reports, Vol. 5, 18319, 17.12.2015.

Research output: Contribution to journalArticle

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abstract = "Intraovarian hyperandrogenism is one of the determining factors of follicular arrest in women with polycystic ovary syndrome (PCOS). Using androgenized rat models, we investigated the effects of androgens on metabolism, as well as on factors involved in follicular arrest and the reduced number of estrus cycles. The dihydrotestosterone (DHT)-treated rats had fewer estrus cycles, higher numbers of large arrested follicles and an increased in body weight gain compared with the dehydroepiandrostenedione (DHEA)- and placebo-treated rats. In cultured rat granulosa cells, DHT suppressed follicle stimulating hormone (FSH)-induced granulosa cell proliferation and increased the accumulation of cells in the G2/M phase. DHT decreased phosphorylated Akt (p-Akt) and cyclin D1 levels through increasing PTEN. DHT-promoted PTEN expression was regulated by peroxisome proliferator-activated receptor gamma (PPAR{\^I} 3) in granulosa cells. Meanwhile, in the large follicles of the DHT-treated rats, the expressions of PPAR{\^I} 3 and PTEN were higher, but the expression of p-Akt and proliferating cell nuclear antigen (PCNA) were lower. Conclusively, DHT and DHEA produced differential effects on metabolism in prepubertal female rats like clinical manifestations of women with PCOS. DHT treatment may affect ovarian follicular maturation by altering granulosa cell proliferation through the regulation of enhancing PPAR{\^I} 3 dependent PTEN/p-Akt expression in the granulosa cells.",
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