The objective of the proposed research is to determine whether a teleost fish, Atlantic croaker, is a reliable model for investigating the effects of chemicals on reproductive endocrine function in female vertebrates. This will be achieved by comparing the effects of lead, benzo(a)pyren, Aroclor 1254 and clomiphene (chemicals representing four classes of reproductive toxins) on reproductive endocrine function in croaker in previously published data on their effects in mammals. The synthesis and actions of gonadal steroids as well as their conjugation and excretion will be investigated both in vivo and in vitro using modern endocrinological techniques. These techniques include radioimmunoassay, radio receptor assay, in vitro steroid biosynthesis from radioactive precursors and separation of products by HPLC and TLC, in vitro oocyte maturation bioassay. Effects of chemicals on the actions of gonadotropin will also be determined using two in vitro bioassays. Indices of reproductive impairment such as ovarian growth, oocyte maturation and ultimate hatching success will also be assessed in order to determine the signficiance of these pertubations in endocrine fucntion. The accumulation of the model compounds by ovarian tissues and oocytes will be measured to determine whether a correlation exists betweent he chemical burden in the organ and the degree of reproductive endocrine dysfunction. These studies will provide valuable new information on the sites and mechanisms of toxicant action on reproductive endocrine function in vertebrates. A long-term goal of this research is to develop this teleost model as an alternative method for assessig the effects of chemicals on endocrine and reproductive function in vertebrates. Potential advantages of using this model are (a) lower costs for animal care, (b) greater public acceptance as test organisms, (c) large amounts of ovarian tissue for in vitro testing, (d) applicability as an early-warning indicator of pollution damage to aquatic ecosystems and the potential reproductive hazards of environmental contamination to human populations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES004214-02
Application #
3252234
Study Section
(SRC)
Project Start
1987-01-01
Project End
1989-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Type
Graduate Schools
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78713
Hawkins, M B; Godwin, J; Crews, D et al. (2005) The distributions of the duplicate oestrogen receptors ER-beta a and ER-beta b in the forebrain of the Atlantic croaker (Micropogonias undulatus): evidence for subfunctionalization after gene duplication. Proc Biol Sci 272:633-41
Zhu, Yong; Rice, Charles D; Pang, Yefei et al. (2003) Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc Natl Acad Sci U S A 100:2231-6
Zhu, Yong; Bond, Jason; Thomas, Peter (2003) Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc Natl Acad Sci U S A 100:2237-42
Thomas, Peter; Zhu, Yong; Pace, Margaret (2002) Progestin membrane receptors involved in the meiotic maturation of teleost oocytes: a review with some new findings. Steroids 67:511-7
Thomas, P; Pinter, J; Das, S (2001) Upregulation of the maturation-inducing steroid membrane receptor in spotted seatrout ovaries by gonadotropin during oocyte maturation and its physiological significance. Biol Reprod 64:21-9
Thomas, P (2000) Chemical interference with genomic and nongenomic actions of steroids in fishes: role of receptor binding. Mar Environ Res 50:127-34
Hawkins, M B; Thornton, J W; Crews, D et al. (2000) Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts. Proc Natl Acad Sci U S A 97:10751-6
Sperry, T S; Thomas, P (2000) Androgen binding profiles of two distinct nuclear androgen receptors in Atlantic croaker (Micropogonias undulatus). J Steroid Biochem Mol Biol 73:93-103
Loomis, A K; Thomas, P (2000) Effects of estrogens and xenoestrogens on androgen production by Atlantic croaker testes in vitro: evidence for a nongenomic action mediated by an estrogen membrane receptor. Biol Reprod 62:995-1004
Sperry, T S; Thomas, P (1999) Identification of two nuclear androgen receptors in kelp bass (Paralabrax clathratus) and their binding affinities for xenobiotics: comparison with Atlantic croaker (Micropogonias undulatus) androgen receptors. Biol Reprod 61:1152-61

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