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Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles.

Wen X, Li D, Tozer AJ, Docherty SM, Iles RK - Reprod. Biol. Endocrinol. (2010)

Bottom Line: With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels.Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize.However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biomedical Sciences, School of Health and Social Science, Middlesex University, The Burroughs, NW4 4BT, UK.

ABSTRACT

Background: The production of sex steroids by follicular cells is proposed to be influenced by the maturity of the incumbent oocyte. Thus steroid levels may reflect suitability of an oocyte for IVF. We examined follicular fluids and granulosa cell production of steroid from IVF patients in order to test the relationship between steroid levels and fertilization.

Methods: Follicular fluid and granulosa cells were extracted from 206 follicles of 35 women undergoing controlled ovarian stimulation. Follicular fluid was assayed for estradiol, progesterone and testosterone. Granulosa cells were cultured from individual follicles and their culture media assayed for production of these hormones after 24 hrs in vitro. Levels of steroids were correlated with follicular diameter, oocyte recovery and subsequent fertilization.

Results: Follicular fluid levels of progesterone were 6100 times higher than that of estradiol, and 16,900 times higher that of testosterone. Despite the size of follicle triggered after controlled luteinization, the levels of progesterone and testosterone were maintained at relatively constant levels (median 98.1 micromoles/L for progesterone, and 5.8 nanomoles/L for testosterone). However, estradiol levels were slightly lower in the larger follicles (follicular diameter 10-15 mm, median 25.3 nanomoles/L; follicles > = 15 mm, median 15.1 nanomoles/L; linear correlation r = -0.47, p < 0.0001). With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels. Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize. Significant quantities of progesterone were produced by the granulosa cells but production was constant regardless of the size of follicle from which the cells originated. Estradiol levels were only detectable in 10 of 121 cultures examined, and testosterone in none. Interestingly, when an oocyte was present follicular estradiol levels correlated with progesterone levels. However, when absent, follicular estradiol levels correlated with testosterone levels but not with progesterone.

Conclusions: The principle steroid product of luteinized pre-ovulatory granulosa is progesterone, a differentiation triggered by the gonadotropin surge. However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize.

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Ovarian follicular steroid synthesis. Diagramatic representation of the steroidogenic pathways in human pre-luteinized follicles (A) and post luteinized follicles (B), demonstrating granulosa dependence on theca cell testosterone steroidogenesis in pre-luteinized follicles and the de novo synthesis of progesterone from cholesterol due to induction/up-regulation of CYP11A and 3βHSD after the gonadotropin surge in post luteinized follicles.
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Figure 5: Ovarian follicular steroid synthesis. Diagramatic representation of the steroidogenic pathways in human pre-luteinized follicles (A) and post luteinized follicles (B), demonstrating granulosa dependence on theca cell testosterone steroidogenesis in pre-luteinized follicles and the de novo synthesis of progesterone from cholesterol due to induction/up-regulation of CYP11A and 3βHSD after the gonadotropin surge in post luteinized follicles.

Mentions: The theca is a very thin layer of cells limited to, and defining, the peripheral boundary of the follicle. These cells express CYP17 as well as 3β-HSD such that further metabolism of either pregnenolone or progesterone (via 17-OH-pregnenolone and 17-OH-pregesterone) to androgens occurs. Thereafter, androgens can diffuse across the basal lamina into granulosa cells where they can be metabolized to estrogens, since these cells specifically express CYP19/aromatase [21] (see figure 5A).


Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles.

Wen X, Li D, Tozer AJ, Docherty SM, Iles RK - Reprod. Biol. Endocrinol. (2010)

Ovarian follicular steroid synthesis. Diagramatic representation of the steroidogenic pathways in human pre-luteinized follicles (A) and post luteinized follicles (B), demonstrating granulosa dependence on theca cell testosterone steroidogenesis in pre-luteinized follicles and the de novo synthesis of progesterone from cholesterol due to induction/up-regulation of CYP11A and 3βHSD after the gonadotropin surge in post luteinized follicles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2958979&req=5

Figure 5: Ovarian follicular steroid synthesis. Diagramatic representation of the steroidogenic pathways in human pre-luteinized follicles (A) and post luteinized follicles (B), demonstrating granulosa dependence on theca cell testosterone steroidogenesis in pre-luteinized follicles and the de novo synthesis of progesterone from cholesterol due to induction/up-regulation of CYP11A and 3βHSD after the gonadotropin surge in post luteinized follicles.
Mentions: The theca is a very thin layer of cells limited to, and defining, the peripheral boundary of the follicle. These cells express CYP17 as well as 3β-HSD such that further metabolism of either pregnenolone or progesterone (via 17-OH-pregnenolone and 17-OH-pregesterone) to androgens occurs. Thereafter, androgens can diffuse across the basal lamina into granulosa cells where they can be metabolized to estrogens, since these cells specifically express CYP19/aromatase [21] (see figure 5A).

Bottom Line: With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels.Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize.However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biomedical Sciences, School of Health and Social Science, Middlesex University, The Burroughs, NW4 4BT, UK.

ABSTRACT

Background: The production of sex steroids by follicular cells is proposed to be influenced by the maturity of the incumbent oocyte. Thus steroid levels may reflect suitability of an oocyte for IVF. We examined follicular fluids and granulosa cell production of steroid from IVF patients in order to test the relationship between steroid levels and fertilization.

Methods: Follicular fluid and granulosa cells were extracted from 206 follicles of 35 women undergoing controlled ovarian stimulation. Follicular fluid was assayed for estradiol, progesterone and testosterone. Granulosa cells were cultured from individual follicles and their culture media assayed for production of these hormones after 24 hrs in vitro. Levels of steroids were correlated with follicular diameter, oocyte recovery and subsequent fertilization.

Results: Follicular fluid levels of progesterone were 6100 times higher than that of estradiol, and 16,900 times higher that of testosterone. Despite the size of follicle triggered after controlled luteinization, the levels of progesterone and testosterone were maintained at relatively constant levels (median 98.1 micromoles/L for progesterone, and 5.8 nanomoles/L for testosterone). However, estradiol levels were slightly lower in the larger follicles (follicular diameter 10-15 mm, median 25.3 nanomoles/L; follicles > = 15 mm, median 15.1 nanomoles/L; linear correlation r = -0.47, p < 0.0001). With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels. Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize. Significant quantities of progesterone were produced by the granulosa cells but production was constant regardless of the size of follicle from which the cells originated. Estradiol levels were only detectable in 10 of 121 cultures examined, and testosterone in none. Interestingly, when an oocyte was present follicular estradiol levels correlated with progesterone levels. However, when absent, follicular estradiol levels correlated with testosterone levels but not with progesterone.

Conclusions: The principle steroid product of luteinized pre-ovulatory granulosa is progesterone, a differentiation triggered by the gonadotropin surge. However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize.

Show MeSH
Related in: MedlinePlus