Upstream eventReduction, Gonadotropins, circulating concentrations
Reduction, Testosterone synthesis by ovarian theca cells
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Directness||Weight of Evidence||Quantitative Understanding|
|Androgen receptor agonism leading to reproductive dysfunction||directly leads to||Strong||Weak|
|fathead minnow||Pimephales promelas||Weak||NCBI|
Life Stage Applicability
|Adult, reproductively mature||Not Specified|
How Does This Key Event Relationship Work
See biological plausibility below.
Weight of Evidence
- In mammals androgen production by theca cells is largely under control of LH (Norris 2007; Young and McNeilly 2010).
- In fish, the differential role of LH versus FSH has been more difficult to define, in part due to the inability to specifically measure LH and FSH in most fish species and the parallel fluctuations of LH and FSH expression in many species.
- Regardless of the differential effects of the two gonadotropins there is little dispute that gonadotropins stimulate gonadal steroid production and that the production of androgens (e.g., androstenedione, testosterone), which are the precursors for estrogen synthesis occurs in the theca cells (Payne and Hales 2004; Young and McNeilly 2010; Miller 1988; Nagahama et al. 1993).
Empirical Support for Linkage
There is a strong weight of evidence establishing the role of gonadotropins in stimulating gonadal steroidogenesis. This relationship is widely accepted.
Uncertainties or Inconsistencies
No significant inconsistencies identified to date, although comprehensive literature review as not conducted.
Quantitative Understanding of the Linkage
Predictive quantitative relationships between circulating gonadotropin concentrations in fish and testosterone synthesis by ovarian theca cells have not been established.
Evidence Supporting Taxonomic Applicability
- A functional hypothalamic-pituitary-gonadal axis involving GnRH and gonadotropin-mediated regulation of reproductive functions is a vertebrate trait (Sower et al. 2009).
- The taxonomic applicability of this key event is limited to chordates.
- CYP11a, one of the critical enzymes for testosterone synthesis has only been found in amphioxus or vertebrates (Baker 2011). Consequently, taxonomic relevance of this KER is likely restricted to that domain.
- Baker ME. Origin and diversification of steroids: co-evolution of enzymes and nuclear receptors. Mol Cell Endocrinol. 2011 Mar 1;334(1-2):14-20. doi:10.1016/j.mce.2010.07.013.
- Miller WL. 1988. Molecular biology of steroid hormone synthesis. Endocrine reviews 9(3): 295-318.
- Nagahama Y, Yoshikumi M, Yamashita M, Sakai N, Tanaka M. 1993. Molecular endocrinology of oocyte growth and maturation in fish. Fish Physiology and Biochemistry 11: 3-14.
- Norris DO. 2007. Vertebrate Endocrinology. Fourth ed. New York: Academic Press.
- Payne AH, Hales DB. 2004. Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocrine reviews 25(6): 947-970.
- Young JM, McNeilly AS. 2010. Theca: the forgotten cell of the ovarian follicle. Reproduction 140(4): 489-504.