Direct inhibition of ovarian steroidogenesis by Cortisol and the modulatory role of 11β‐hydroxysteroid dehydrogenase

Abstract

Cortisol acts directly in human granulosa-lutein cells to inhibit the support of steroidogenesis by LH and this interaction is modulated by ovarian 11 beta HSD in the majority of patients.

Steroid Receptors in the Uterus and Ovary

“…735 Glucocorticoid signaling in the ovary acts to inhibit LH action and steroid biosynthesis during folliculogenesis. 736 Treatment of granulosa cells with cortisol or dexamethasone was able to inhibit FSH-stimulated increases in aromatase activity in vitro, while P production was increased compared to control-treated cells. This finding suggests that GR signaling may affect steroidogenesis of the ovarian steroids in a differential manner.…”

“…To circumvent the action of glucocorticoids, expression of two metabolizing enzymes has been found to have stage-specific expression in the ovary. 736 The expression of the type I and type II 11β-hydroxysteroid dehydrogenase (11HSD 1 and 11HSD 2) modulates the action of glucocorticoids by regulating their concentrations within tissues. 739 This is important in the ovary during folliculogenesis since glucocorticoids are not synthesized within the tissue itself.…”

Dehydroepiandrosterone in follicular fluid is produced locally, and levels correlate negatively with in vitro fertilization outcomes

“…One possible mechanism may be via the action of glucocorticoids. There is evidence that elevated levels of DHEA and DHEAS are associated with increased cortisol (7), which can directly inhibit steroidogenesis (8). In turn, higher FF cortisol has been shown to be associated with negative IVF outcomes (6,8).…”

Seasonal variation in corticosterone receptor binding in brain, hippocampus, and gonads in House Sparrows (Passer domesticus)

“…Although there is significant GR and MR binding in House Sparrow testes and ovary (Lattin et al 2012b), and CORT can suppress steroidogenesis and other reproductive processes by acting directly on the gonads (Hsueh and Erickson 1978, Sapolsky 1985, Consten et al 2002, 11β hydroxysteroid dehydrogenase type 2, which converts CORT into an inactive metabolite, may also be present in these tissues, as it is in the gonads of other animals (Michael et al 1993, Monder et al 1994, Denari and Ceballos 2005. This may prevent CORT from binding to gonadal GR and MR in situations of short-term stress and could be the reason that the short-term down-regulation of reproduction by stress seems to happen primarily via regulation at the brain and pituitary (Rivier andRivest 1991, Breen andKarsch 2006).…”