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Fish Reproductive Physiology/ Marine Environmental Toxicology
CORE RESEARCH AREAS Steroid Hormone Receptors: Genomic and Nongenomic Mechanisms
CURRENT PROJECTS Characterization of mPRs in human breast cancer Regulation and function of a progestin receptor on fish sperm membranes. (U.S. Dept. of Agriculture) Effects of Hypoxia on the Gulf of Mexico (National Oceanic and Atmospheric Association) RECENT PUBLICATIONS (includes some abstracts) CURRENT GRADUATE STUDENTS AND ASSOCIATES
CORE RESEARCH AREAS Steroid Hormone Receptors: Genomic and Nongenomic Mechanisms
We are studying both nuclear and plasma membrane steroid receptors for estrogens, androgens and progestins in marine fish and their roles in reproduction.
For additional information, please look at our recent publications.
A major research emphasis in
our laboratory has been to identify the mechanisms by which chemicals can
interfere with reproductive endocrine function in the croaker and seatrout
models. A wide variety of chemicals can disrupt chemical processes by
binding to hormone receptors. If chemical binding causes activation of the
receptor leading to a hormonal response, the chemical acts as a hormonal
mimic. We and others have shown that o,p'-DDT, nonylphenol and
hydroxylated PCBs act in this way on the nuclear estrogen receptor, causing an
estrogenic response. On the other hand, if binding of the chemical to the
receptor does not activate Studies are also being conducted on chemical disturbance of hormone signaling pathways at sites distal to binding of the hormone to its receptor. For example, we have obtained evidence that cadmium can disturb gonadotropin and estrogen secretion by by interfering with calcium signaling and the adenylate cyclase system, respectively.
Another major project is to determine the mechanisms of neuroendocrine toxicity by environmental chemicals. Many chemicals are known to be neurotoxic, but their actions on the neuroendocrine system and the reproductive consequences are largely unknown. Our studies have shown that PCBs disrupt reproductive cycles by inhibiting an enzyme involved in the synthesis of serotonin, a neurotransmitter which has a stimulatory influence on gonadotropin secretion. The results of this project, funded by the National Institutes of Health, have important implications for human health.
The endocrine parameters altered in the controlled laboratory exposures have also been evaluated as biomarkers of exposure to endocrine disrupting chemicals in field studies in Texas, California and elsewhere. Currently, male croaker populations from contaminated and relatively clean sites in Texas bays and estuaries are being assessed for evidence of feminization and testicular dysfunction. For additional information, please look at our recent publications.
Teleost fishes are particularly suitable models to study mechanisms of neuroendocrine control of reproduction because of their relatively simple neuroendocrine organization. They are unique among vertebrates in that they lack the specialized pituitary portal system present in tetrapods that delivers brain regulators to specific areas of pituitary. Instead, releasing hormones and neurotransmitter neurons directly innervate the pituitary gland in teleosts. In addition, hormone producing cells in the pituitary show a markedly distinct distribution pattern that facilitates studies on their innervation and neurotransmitter control (Fig. 3).
Fig 3: Direct innervation of teleost pituitary by stimulatory and inhibitory pathways originating from preoptic anterior hypothalamic area
Applications Aquaculture. One of the major problems in aquaculture of most fishes is the lack of spontaneous spawning in captivity due primarily to the absence of appropriate environmental and social cues resulting in alterations of normal neuroendocrine processes. Therefore, an understanding of neuroendocrine mechanisms involved in the control of final stages of gamete maturation is essential for the development of new and improved methods of induced breeding of captive broodstocks.
Neuroendocrine
toxicology. Our research in basic neuroendocrinology has helped investigate
novel mechanisms of neuroendocrine toxicity of environmental pollutants, such as
PCBs, DDTs, and heavy metals that can disrupt vertebrate reproduction. These
studies have established Atlantic croaker as an excellent vertebrate model to
investigate mechanisms of neuroendocrine control of reproduction and
perturbation of neuroendocrine pathways by environ For additional information, please look at our recent publications.
Research in our laboratory
has focused on the hormonal control of oocyte and sperm maturation; in
particular, the roles of membrane receptors for the maturation-inducing steroid
(20b-S), and
gap junctions and connexin genes. We have found that fully grown oocytes
need to be exposed to gonadotropin in order to become responsive to 20b-S
and undergo meiotic maturation. Further, upregulation of the 20b-S
receptor and gap junction formation appear to be key events in the development
of oocyte responsiveness to 20b-S
during the preovulatory surge in gonadotropin
We have recently demontrated that 20b-S also exerts a direct effect on fish sperm, causing a dose-dependent increase in sperm motility after one minute exposure (fig 6). Moreover, a specific receptor for 20b-S has been identified on sperm membranes which is the likely mediator of the steroid's action.
Another interest is the modulation of steroid hormone secretion by steroids themselves, especially those involving nongenomic mechanisms. For example, we have found that estrogens, which are produced in small amounts in the testis, down-regulate androgen production in that tissue by a nongenomic action and that several estrogenic pesticides can also act via this mechanism.
For additional information, please look at our recent publications.
Characterization of membrane Progesterone Receptor A novel membrane localized progestin receptor was first identified in spotted seatrout ovary and was shown to induce final oocyte maturation prior to spawning. An analogous protein has also been found in humans. Studies on the structure as well as the functions of the mPRs in various species and tissues continue.
Characterization of mPRs in human breast cancer Breast cancer will affect more than one in ten women in the US. Many breast tumors are steroid dependant and while estrogen has been the main treatment target evidence is suggesting the progesterone is also important in tumor development and growth. Current work in the lab examines the roles of mPRs in human breast cancer cell lines and expression in breast tumors.
Regulation and function of a progestin receptor on fish sperm membranes. (U.S. Dept. of Agriculture)
Fertilization success in fishes is greatly influenced by the quality of sperm released by the males. Sperm motility varies considerably in many important aquaculture species both between models and also within the same individual at different stages of the reproductive cycle, but their underlying causes are unknown. The purpose of this project is to obtain a better understanding of the mechanisms by which sperm activation and sperm quality are regulated by a progestin steroid hormone (20b-S) in the Atlantic croaker. Recently, we discovered that 20b-S can act directly on sperm to increase its motility and fertilization capability. Moreover, we identified a specific receptor for 20b-S on croaker sperm membranes, the first described in any fish species. We propose that this sperm progestin receptor is a critical component of the regulatory system for sperm activation. We are investigating whether progestin receptor concentrations influence hormonal activation of sperm, the intracellular changes in Ca2+ and cyclic AMP induced by binding of 20b-S to its receptor, and their effects on sperm motility and fertilization capability. We expect that fundamental aspects of this study will be broadly applicable to important aquaculture species and will be the basis for the development of effective hormonal treatments to enhance sperm quality in fish species of aquaculture importance.
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Effects of Hypoxia in
the Gulf of Mexico (NOAA) The dead zone is an area of the Gulf of Mexico off the Louisiana coast where extremely low oxygen levels (hypoxia) at the ocean floor have killed or forced out marine organisms. Increased nutrients in the Mississippi River from fertilizer runoff and sewage effluent causes a larger than normal algae bloom in the Gulf shelf waters which eventually sinks and consumes oxygen as it decomposes. As the nutrient content of the Mississippi changes seasonally the size of the dead zone waxes and wanes. In the winter it is small or undetectable and grows to the size of New Jersey in the summer. This area is home to many commercially and ecologically important marine
species. The Atlantic croaker, a common Gulf fish and a model species for
research, spawns in the late summer and autumn and a period of severe
hypoxia may interrupt reproduction. This project is investigating the
effects of severe hypoxia on the reproductive ability and success of
Atlantic croaker.
This project has both a field component to establish the natural condition and the reactions of fish to the dead zone in the wild and a lab component to determine the mechanisms behind phenomena observed in the field. This research is apart of a much larger project funded by NOAA that involves numerous scientist from several universities and various expertise in marine science. Back to top |
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Steroid hormones
and their receptors are of central importance in the endocrine control of a wide
variety of physiological functions critical for the survival and propagation of
a species, such as reproduction, behavior, salt balance, metabolism, immune
function and resistance to stress. Steroids have been shown to influence
many of these processes by freely diffusing into the cell and binding to
specific intracellular receptors. Activation of these nuclear steroid
receptors by the hormone enables them to bind to specific hormone response
elements on genes, resulting in alterations in their rates of transcription and
subsequently protein synthesis (fig 1.) This classical genomic mechanism of
steroid action is typically slow. However, over the past fifteen years,
convincing evidence has been obtained from many laboratories using a wide
variety of animal and cell models that steroids also exert rapid actions at the
cell-surface which are often nongenomic and instead involve activation of
intracellular second messenger pathways (fig 1). Moreover, specific steroid
receptors have been identified on the plasma membranes of target tissues which
are the likely mediators of these nongenomic steroid actions.
Molecular studies have resulted in the discovery of
a third nuclear estrogen receptor in Atlantic croaker, the only vertebrate
species to date in which three estrogen receptors have been identified.
Another cloning project has resulted in the first identification of a putative steroid membrane receptor gene. 
There is growing concern over
recent reports of reproductive impairment and developmental abnormalities in
fish and wildlife environmentally exposed to endocrine disrupting
chemicals. Feminization of males birds, alligators and fishes, the
production of the estrogen-induced yolk precursor, vitellogenin, in male fish,
altered endocrine function in females and decreased reproductive success have
been reported after exposure to a growing list of environmental contaminants
including DDT, PCBs, pesticides, surfactants, plasticizers and heavy metals. It
has been suggested that the increases in the incidence of breast and prostate
cancers and decreased fertility and sperm counts in human populations are also
due to environmental exposure to endocrine disrupting chemicals. However,
our incomplete knowledge of the causes, consequences, and extent of endocrine
disruption in vertebrates limits our ability to estimate the ecological and
human health hazards of environmental exposure to endocrine disrupting
chemicals.
the receptor, no hormonal response occurs and the
natural hormone cannot occupy the binding site, so the chemical acts as an
antagonist (fig 2). A variety of organochlorine pesticides antagonize the actions
of testosterone and progestins by this mechanism. Recently we have
obtained the first clear evidence that these chemicals can also interfere with
nongenomic steroid actions on oocytes, sperm and testes by binding to their
steroid membrane receptors.
mental chemicals. A better
understanding of these mechanisms will help design specific drugs to treat the
problems associated with neuroendocrine impairments induced by exposure to toxic
environmental chemicals. We have found for the first time in a vertebrate
species, Atlantic croaker, that a polychlorinated biphenyl mixture (Aroclor
1254, PCB) impairs LH secretion by inhibiting hypothalamic tryptophan
hydroxylase (TPH), the rate-limiting enzyme in 5-HT synthesis (fig 5). In addition to
the evidence of neuroendocrine disruption, this finding may have broad
implications for mental health in PCB exposed human populations.
The marked morphological and
physiological changes associated with oocyte and sperm production which occur in
the gonads during the reproductive cycle are under complex endocrine
control. However, despite intensive research efforts, the hormone
regulation of many aspects of gonadal and gamete functions remain poorly
understood.
secretion.
