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Key Event Relationship Overview

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Description of Relationship

Upstream Event Downstream Event/Outcome
Gonadotropins, circulating concentrations, Reduction Testosterone synthesis by ovarian theca cells, Reduction

AOPs Referencing Relationship

AOP Name Type of Relationship Weight of Evidence Quantitative Understanding
Androgen receptor agonism leading to reproductive dysfunction Directly Leads to Strong Weak

Taxonomic Applicability

Name Scientific Name Evidence Links

How Does This Key Event Relationship Work

Weight of Evidence

Biological Plausibility

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. However, 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

Include consideration of temporal concordance here

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

Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?

Predictive quantitative relationships between circulating gonadotropin concentrations in fish and testosterone synthesis by ovarian theca cells have not been established.

Evidence Supporting Taxonomic Applicability


  • Norris DO. 2007. Vertebrate Endocrinology. Fourth ed. New York: Academic Press.
  • Young JM, McNeilly AS. 2010. Theca: the forgotten cell of the ovarian follicle. Reproduction 140(4): 489-504.
  • Payne AH, Hales DB. 2004. Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocrine reviews 25(6): 947-970.
  • 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.