Sex steroid feedback regulation of pituitary gonadotropins during early secondary oocyte growth in coho salmon (Oncorhynchus kisutch) – a potential target of endocrine disruption.

Thesis (Ph.D.)--University of Washington, 2016-06

In teleost fish as in other vertebrate species, the pituitary gonadotropins, follicle-stimulating hormone (Fsh) and luteinizing hormone (Lh), are fundamentally involved in regulating physiological processes critical to the production of a fertilizable egg, including steroidogenesis, folliculogenesis, vitellogenesis, final oocyte maturation, and ovulation. Despite the importance of pituitary gonadotropins (Gths) in regulating fish reproduction, the complex network of factors regulating Gth synthesis and release in fishes is still not fully understood. Further, in the growing field of endocrine disruption, only limited data are available on impacts of endocrine disrupting chemicals (EDCs) on the gonadotropins or pituitary function. The research described in this dissertation examines the role of sex steroids in regulating Fsh and Lh during early stages of oogenesis in salmon and determines if chemicals or natural steroids in the environment originating from waste-water treatment plants (WWTPs) could disrupt reproduction via altered GtH expression. The study described in the first chapter demonstrates that of estrogen differentially regulates Fsh and Lh in female coho salmon during the transition from late primary to early secondary oocyte growth, which corresponds to the onset of puberty in fish. In chapter 2, I report the results of the first transcriptome-wide gene expression analysis of the pituitary gland in prepubertal salmon exposed to water containing ethynylestradiol (EE2), a synthetic estrogen used in human contraceptives that enters the aquatic ecosystem via WWTP discharges. Lastly, the work presented in chapter 3 provides evidence that pituitary Gths, primarily Lh, are differentially expressed in coho salmon exposed to WWTP effluents, likely due to presence of estrogenic chemicals. This research demonstrates that natural and synthetic estrogens differentially regulate Fsh and Lh as well as numerous genes involved in pathways associated with Gth synthesis and secretion, steroid action, cell development and circadian rhythms. By combining basic and applied research, this work has provided valuable information on sex steroid regulation of Gths during early oogenesis that will be useful for predicting and interpreting results of endocrine disruption research. Further, the results of this work suggest that one mechanism of endocrine disruption in fish could be via disrupted gonadotropin synthesis.