Tyrone B Hayes

• University of California, Berkeley

Endocrine research in animals often entails exogenous hormone administration. Special issues arise when developing administration protocols for hormones with circadian and seasonal periodicity. This article reviews various methods for the exogenous administration of hormones with such periodicities by focusing on melatonin. We discuss that methodol...

Nitrate is heavily used as an agricultural fertilizer and is today a ubiquitous environmental pollutant. Environmental endocrine effects caused by nitrate have received increasing attention over the last 15 years. Nitrate is hypothesized to interfere with thyroid and steroid hormone homeostasis and developmental and reproductive endpoints. The curr...

We are now living in the Anthropocene, the first time in Earth’s history when synthetic chemicals—created by humans—are damaging the planet and contributing to a major loss of biodiversity. Pesticides are a particular problem in this regard. Agricultural practices changed dramatically following World War II. Methods for the production of nitrogen f...

This paper describes a novel analytical methodology for the simultaneous determination of absolute and total concentrations of 11 native thyroid hormones and associated metabolites, viz. thyroxine (T4), 3,3′, 5-triiodothyronine (T3), 3,3′, 5′-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3′- diiodothyronine (3,3′-T2), 3-iodothyronine (T1)...

The effect of long-term stress on amphibian immunity is not well understood. We modeled a long-term endocrine stress scenario by elevating plasma corticosterone in two species of amphibians and examined effects on white blood cell differentials and innate immune activity. Plasma corticosterone was elevated in American bullfrogs (Lithobates catesbei...

This paper presents the development, optimization, and validation of a LC-MS/MS methodology to determine the concentration of the antifungal drug and fungicide tebuconazole in a controlled exposure study of African clawed frogs (Xenopus laevis). The method is validated on animal tank water and on tissue from exposed and non-exposed adult X. laevis....

Extensive corn production in the midwestern United States has physically eliminated or fragmented vast areas of historical amphibian habitat. Midwestern corn farmers also apply large quantities of fertilizers and herbicides, which can cause direct and indirect effects on amphibians. Limited field research regarding the statuses of midwestern amphib...

Public health research suggests the industrialized U.S. food system is at odds with the health of children. Industrialization refers to the fact that it is a food system reliant on chemical and fossil-fuel intensive inputs, including synthetic fertilizers and pesticides. In terms of the latter, public health concerns include contamination of foodst...

The continued presence of gonadotropin-releasing hormone (GnRH) neurons is required for a healthy reproductive lifespan, but factors that maintain postnatal GnRH neurons have not been identified. To begin to understand these factors, we investigated whether (1) fibroblast growth factor (FGF) signaling and (2) interactions with the opposite sex are...

A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical’s potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regu...

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of "the dose makes the poison," because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-d...

The herbicide atrazine is a potent endocrine disruptor, active in fish and amphibians in the low ppb range. Among other effects, atrazine impairs reproductive development and function including decreased testosterone levels, impaired testicular development, and low fertility/sperm production in male fish, amphibians, and in some reptiles. Atrazine...

I am honored to receive the E. E. Just Award for 2010. In my invited essay, I have opted to discuss the state of diversity in the biological sciences with some recommendations for moving forward toward a more positive and inclusive academy. The need to develop cohorts of minority scientists as support groups and to serve as role models within our i...

Greater than 70% of the world's amphibian species are in decline. We propose that there is probably not a single cause for global amphibian declines and present a three-tiered hierarchical approach that addresses interactions among and between ultimate and proximate factors that contribute to amphibian declines. There are two immediate (proximate)...

The herbicide atrazine is one of the most commonly applied pesticides in the world. As a result, atrazine is the most commonly detected pesticide contaminant of ground, surface, and drinking water. Atrazine is also a potent endocrine disruptor that is active at low, ecologically relevant concentrations. Previous studies showed that atrazine adverse...

Recent studies from my laboratory, showing the chemical castration (demasculinization) and feminization of amphibians by low but ecologically relevant concentrations of atrazine in the laboratory and in the wild, prompted a critical response from atrazine's manufacturer, Syngenta Crop Protection, and Syngenta-funded scientists. A careful analysis o...

Atrazine is a potent endocrine disruptor that increases aromatase expression in some human cancer cell lines. The mechanism involves the inhibition of phosphodiesterase and subsequent elevation of cAMP. We compared steroidogenic factor 1 (SF-1) expression in atrazine responsive and non-responsive cell lines and transfected SF-1 into nonresponsive c...

The popular herbicide atrazine is an endocrine disruptor that demasculinizes and feminizes several species of animals, and co-relates with breast and reproductive disorders in mammalians. We recently reported that atrazine induces human aromatase gene expression via promoter II (ArPII) in a steroidogenic factor 1 (SF-1)-dependent manner. Here, we s...

Amphibian populations are declining globally at an alarming rate. Pesticides are among a number of proposed causes for these declines. Although a sizable database examining effects of pesticides on amphibians exists, the vast majority of these studies focus on toxicological effects (lethality, external malformations, etc.) at relatively high doses...

Atrazine is a potent endocrine disruptor that both chemically castrates and feminizes male amphibians. It depletes androgens in adult frogs and reduces androgen-dependent growth of the larynx in developing male larvae. It also disrupts normal gonadal development and feminizes the gonads of developing males. Gonadal malformations induced by atrazine...

Hormonal control of post-embryonic morphogenesis is well established, but it is not clear how differences in developmental endocrinology between species may underlie animal diversity. We studied this issue by comparing metamorphic thyroid hormone (TH) physiology and gonad development across spadefoot toad species divergent in metamorphic rate. Tiss...

Concern continues to grow over the negative impact of endocrine disrupting chemicals on environmental and public health. The number of identified endocrine disrupting chemicals is increasing, but biological endpoints, experimental design, and approaches for examining and assessing the impact of these chemicals are still debated. Although some worke...

This paper will review briefly the use of wildlife as models in the study of how mix- tures, low doses, and the embryonic environment modulate the action of endocrine active substances (EASs). In so doing, it will show how the issue of low dosages must be consid- ered within the context of mixtures present in the environment and the endocrine backg...

Atrazine is the most commonly used herbicide in the United States and probably the world. Atrazine contamination is widespread and can be present in excess of 1.0 ppb even in precipitation and in areas where it is not used. In the current study, we showed that atrazine exposure (> or = to 0.1 ppb) resulted in retarded gonadal development (gonadal d...

Atrazine is the most commonly used herbicide in the United States and probably in the world. Here we investigate the effects of exposure to water-borne atrazine contamination on wild leopard frogs (Rana pipiens) in different regions of the United States and find that 10-92% of males show gonadal abnormalities such as retarded development and hermap...

Atrazine is the most commonly used herbicide in the U.S. and probably the world. It can be present at several parts per million in agricultural runoff and can reach 40 parts per billion (ppb) in precipitation. We examined the effects of atrazine on sexual development in African clawed frogs (Xenopus laevis). Larvae were exposed to atrazine (0.01-20...

The larvae of spadefoot toads exhibit extreme developmental/endocrinological diversity. For example, New World spadefoot toads (Scaphiopus and Spea) have the shortest larval periods known among anurans, and the tadpoles of Old World spadefoot taxa (Pelobates) are among the largest known. To analyze the patterns of this diversity in an evolutionary...

To study the effects of glucocorticoids and IGF-I on the modulation of growth in the tilapia Oreochromis mossambicus, we employed an epiceratobranchial cartilage radioisotope incorporation assay, wherein radiolabeled sulfate and thymidine uptakes are measured in vitro to indicate proteoglycan synthesis and cell proliferation, respectively. Cartilag...

Increasing density reduces larval growth and development in many anuran larvae including those of the western toad (Bufo boreas). We have shown that whole body corticosterone levels also increase in proportion to density. These data, along with the inhibition of larval growth and development induced by exogenous corticosterone, suggest a causative...

The spadefoot toad Scaphiopus couchii lives in desert environments and has the shortest larval period known among anurans. We compared the larval period of Sc. couchii with that of a sympatric relative, Spea multiplicata, under identical laboratory conditions. It was possible that (A) Sp, multiplicata might metamorphose as fast as Sc. couchii when...

Organochlorine compounds such as o,p'DDT can mimic estrogen effects. We compared the effects of o,p'DDT and six other DDT congeners to the effects of estradiol by comparing in vivo color changes in the reed frog (Hyperolius argus). Premature female color pattern induction in H. argus is specific to estrogens and the current study suggests that this...

The current study examined the role of steroids in primary and secondary sex differentiation in the African reedfrog (Hyperolius argus: Hyperolidae). This species is sexually dimorphic: males have a solid green dorsum and females are reddish-brown with large white spots. This study is the first to report the effects of sex steroids on the developme...

Most amphibians lack morphologically distinguishable sex chromosomes, but a number of experimental techniques have shown that amphibian sex determination is controlled genetically. The few studies suggesting that environment influences sex determination in amphibians have all been conducted at temperatures outside of the range normally experienced...

Morphologically distinct secretory cells in the pituitary pars distalis and pars tuberalis of larval and adult toads (Bufo boreas) immunoreactive cells in the pars distalis. Thyrotropin immunoactivity appears in pars tuberalis and pars distalis before gonadotropin immunoreactivity during early development. Antisera which distinguish gonadotropes (s...

According to common understanding of sexual differentiation, the formation and development of a penile clitoris in female spotted hyaenas requires the presence of naturally circulating androgens during fetal life. The purpose of the present study was to determine potential source(s) of such fetal androgens by investigating the timing of urogenital...

Developmental constraints are limitations on phenotypic variability resulting from developmental mechanisms that produce biases in phenotypic variants and hence evolution. These constraints ultimately limit the available phenotypes on which selection can act. Because hormones play important roles in many developmental processes, there is a great po...

Exposure of tadpoles to dichlorodiphenyl trichloroethane (DDT) induces pathological development of the upper mandible. In the current study, we report a similar pathological development after tadpoles of the Senegal walking frog (Kassina senegalensis: Hyperolidae) were treated with the steroid hormone, corticosterone (CORT) for 5 d at 1.1 μM. Corti...

Amphibian metamorphosis is a complex process regulated by a number of external (environmental) and internal (hormonal) processes. The transformation from larval to adult form in amphibians provides excellent models for developmental biologists exam- ining tissue and cell differentiation and mor- phogenesis. Metamorphosis is also an ex- cellent mode...

SYNOPSIS. Anuran metamorphosis is controlled by the complex interaction of several hormones. Although thyroid hormone is the major stimulatory hormone in metamorphosis and likely regulates all of the metamorphic genes directly, other hormones are involved in regulating thyroid hormone secretion and activity. Corticoids (in particular corticosterone...

The effects of corticosterone (CORT)-treatment on various tissues were examined in two species of anuran larvae, the discoglossid Bombina orientalis, and the bufonid Bufo boreas. Corticosterone was administered directly into aquarium water for 15 days. After treatment, histological analyses were conducted on skin, gut, spleen, thymus, and neural an...

At metamorphic climax, anurans develop skin glands that migrate from the epidermis into the dermis. Thyroxine (T4) stimulates skin gland differentiation and migration, and a previous study showed that corticosterone (Cort) treatment of larvae is inhibitory. The current study used histological analyses to address the mechanism of Cort's prevention o...

Typically, the role of corticosterone(B) in metamorphosis is considered secondary to that of thyroid hormone, with B having only enhancing effects. In the current study, we demonstrate that the relationship between the thyroid hormones and B is much more complex and that thyroxine (T4) may depend on B for some of its functions. Tadpoles of the west...

The effects of experimental conditions--steroid concentration, temperature, treatment duration, tadpole density, and delivery mode--on testosterone (T) metabolic rates were examined in larval anurans. T uptake into tadpoles was measured by scintillation counting of [3H]T and metabolism of T was studied by thin layer chromatography in two anuran spe...

In a previous study (Hayes et al. [1993] J. Exp. Zool., 266:206-215), we demonstrated that exogenous corticosterone (B) inhibited growth, and had varied effects on development and metamorphosis in the toad (Bufo boreas). The current study determined the relation between the actions of B and thyroid hormones on body growth (length and weight), tail...

Both 17 beta-estradiol (E2) and testosterone (T) were shown to inhibit in vitro pituitary LH secretion in the turtle Trachemys scripta. Since T was approximately 500 times less potent than E2, and 5 alpha-dihydrotestosterone was even less active than T, the inhibitory action of T may result from its aromatization to estrogen. We utilized both in vi...

Although generally viewed as only synergistic with the thyroid hormones, corticosterone (CORT) has many independent effects on anuran larval development. CORT enhances thyroid hormone-induced tail resorption and is involved in immune system, skin gland and gut differentiation. Interactions between the hypothalamo-pituitary-thyroid axis and the cort...

Uptake and metabolism of exogenous steroids [testosterone (T), estradiol (E2), and corticosterone (B)] were examined in anuran larvae. Radioimmunoassay (RIA) of steroids dissolved in water revealed that as much as 0.03 mg of T or E2 were cleared from water by a single Xenopus laevis tadpole in 24 hr. Studies using RIA in combination with counting o...

The effects of temperature and steroids [testosterone (T), estradiol (E 2 ), and cortico‐sterone (B)] on premetamorphic growth and development were investigated in the toad (Bufo boreas). The effects of steroids were both temperature and age dependent. In the first experiment, steroids (1.1–1.4 μM) were administered by dissolving them in the water...

Sexual size dimorphism was investigated in the African bullfrog (Pyxicephalus adspersus), a species in which adult males are about 2.5 times larger than females. Growth profile analysis revealed that males and females begin to diverge in growth rates at 4 weeks postmetamorphosis, concurrent with the appearance of differentiated gonads. At the end o...

agricultural runoff and can reach 40 parts per billion (ppb) in fe precipitation. We examined the effects of atrazine on sexual R development in African clawed frogs (Xenopus laevis). Larvae were te exposed to atrazine (0.01-200 ppb) by immersion throughout A larval development, and we examined gonadal histology and at laryngeal size at metamorphos...

Thesis (Ph. D. in Integrative Biology)--University of California, Berkeley, Dec. 1993. Includes bibliographical references.