Androgen and Follicle-Stimulating Hormone Interactions in Primate Ovarian Follicle Development

Abstract

We have previously shown that androgens stimulate early stages of follicular development and that granulosal androgen receptor (AR) gene expression is positively correlated with follicular growth. The present study was aimed at elucidating potential interactions between FSH and androgens in follicular development. Study groups included eight normal cycling rhesus monkeys (five follicular and three luteal-phase), eight testosterone (T)-treated, and four FSH-treated animals. Examination of sequential ovary sections revealed selective colocalization of AR and FSH receptor (FSHR) messenger RNAs (mRNAs) in healthy, growing follicles. Moreover, individual follicles demonstrate a highly significant (P < 0.001) positive correlation between FSHR and AR mRNA levels in all study groups. Androgen treatment significantly increased granulosa cell FSHR mRNA abundance (by approximately 50-100%, depending on follicle size). FSH treatment increased granulosa AR mRNA levels only in primary follicles. The finding that T augments follicular FSHR expression suggests that androgens promote follicular growth and estrogen biosynthesis indirectly, by amplifying FSH effect, and may partially explain the enhanced responsiveness to gonadotropin stimulation noted in women with polycystic ovary syndrome.

Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation

“…PCOS-related hyperandrogenism can exerts complex effects on the ovarian follicle. Data from microarray studies indicate that androgen might play a role in up-regulate gene expression in PCOS oocytes [5] and androgen treatment in female rhesus monkeys increases mRNA expression of FSH and IGF-1 receptors in granulosa cells and follicle primordial oocytes [39]. In bovine granulosa cells, estrogen used alone and in combination with FSH has been shown to up-regulate BMPR2 mRNA expression [22,24].…”

Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation

“…Additionally, aromatase knockout mice presented with disrupted folliculogenesis, ovulation failure and elevated serum LH and FSH levels due to androgen/estrogen level imbalance [31]. Finally, the use of aromatase inhibitors during ovarian stimulation for intrauterine insemination has led to significantly lower amounts of large follicles compared to the control group [32], presumably due to reduced serum estrogen levels and to increased ovarian follicular FSH receptor mRNA [33]. Taking into account the association of short CYP19(TTTA) n alleles with reduced aromatase activity and lower serum estrogen levels, our results concerning follicular number and size, are indirectly supported.…”

Women with high telomerase activity in luteinised granulosa cells have a higher pregnancy rate during in vitro fertilisation treatment

“…However, why is the normal level of T during the menstrual period (early follicular phase) positively correlated with TA in luteinised GCs? This finding may be related to the proliferation and development of GCs through the enhanced functions of FSH [37], GDF-9 [38], IGF-1 [39,40] and their receptors after stimulation by T during the early stage of follicular development. It has been widely reported that, at the early stages of follicular development, androgens produced by thecal cells under LH stimulation act as an enhancer of FSH-stimulated follicular differentiation.…”