Development-related increase in cortisol biosynthesis by human granulosa cells

Area of Science:

• Reproductive Endocrinology
• Steroid Metabolism
• Ovulation Biology

Background:

• Anti-inflammatory mechanisms are crucial for ovulation.
• Cortisol (F) is a key anti-inflammatory hormone.
• 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) converts cortisone (E) to cortisol (F).

Purpose of the Study:

• To investigate the role and regulation of 11betaHSD1 in human granulosa cells during ovulation.
• To determine if 11betaHSD1 activity differs between immature and periovulatory follicles.
• To assess the impact of gonadotropins on 11betaHSD1 activity.

Main Methods:

• Isolation of granulosa cells (GC) and thecal cells (TC) from human ovaries.
• Measurement of 11betaHSD enzyme activity using radiolabeled substrates (E and F).
• Assessment of gene expression for 11betaHSD1 and 11betaHSD2.
• Hormonal stimulation of GC with follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

Main Results:

• Luteinized granulosa cells (LGC) from periovulatory follicles efficiently converted cortisone to cortisol (E to F).
• Immature granulosa cells (IGC) and thecal cells (TC) showed minimal E to F conversion.
• All cell types could convert cortisol to cortisone (F to E), with higher activity in LGC.
• Follicular fluid F and F:E ratios were higher in periovulatory follicles.
• FSH stimulation increased 11betaHSD1 activity in IGC, paralleling estrogen and progesterone synthesis.

Conclusions:

• 11betaHSD1 activity in the human ovary is developmentally regulated and responsive to gonadotropins.
• Increased E to F conversion by LGC in periovulatory follicles supports a local anti-inflammatory role for cortisol during ovulation.
• The expression and activity of 11betaHSD enzymes are critical for regulating local cortisol levels at ovulation.